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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 397 records · Page 22Linked to original sources

Extraocular muscle changes after cryotherapy for retinopathy of prematurity and the development of strabismus in premature infants.

To find out whether the cryotherapy for the treatment of the retinopathy of prematurity (ROP) causes structural changes of the extraocular muscle (EOM), and also whether the changes are related with the occurrence of strabismus. To examine the acute stage change, we conducted a transconjunctival cryotherapy around the superior rectus muscle of a rabbit and resected it 0, 3, 7, 14, and 28 days after the cryotherapy. In observing chronic changes, we first categorized patients who had an esotropia surgery into groups, one of which combined prematurity and cryotherapy and one group affected by prematurity but without having had cryotherapy. Then we compared the change of EOM with that of a fullterm infant group. In a rabbit, edema, acute inflammatory cells and a large amount of degenerated muscle fibers were observed immediately after the cryotherapy and on the 3rd day. On the 7th day, regenerated muscle fibers were observed and on the 14th day, the inflammatory cells decreased and the amount of regenerated muscle fiber increased. On the 28th day, abnormal findings were not observed any more and the muscle was found to be normal. When chronic changes of EOM in human on 1 1/2 to 8 1/2 years after cryotherapy, there were no abnormal findings observed in three groups. From the study, we can infer that cryotherapy can cause acute inflammation and necrosis of muscle fiber but such an acute change will improve and does not result in structural change in the long term. Therefore, the occurrence of strabismus in patients with ROP is considered to be attributable to reasons other than injury of EOM.

Animals↗

Altered renal expression of aquaporin-2 water channels in rats with experimental two-kidney, one clip hypertension.

The present study was aimed at examining the regulation of aquaporin (AQP)-2 water channels in the kidney in two-kidney, one clip (2K1C) hypertension. Rats were made 2K1C hypertensive for 6 weeks, and their expression of AQP2 channel proteins was determined in the clipped and contralateral kidneys. To examine the upstream affecting AQP2 channels, adenylyl cyclase activity was also determined. Along with the hypertension, in the clipped kidney, the abundance of AQP2 proteins was significantly decreased in the cortex, outer and inner medulla, while their trafficking remained unaltered. Concomitantly with the reversal of the blood pressure at 24 hours following removal of the clip, the AQP2 abundance also returned to the control level. The arginine vasopressin-evoked generation of cAMP was decreased in the clipped kidney, which again was reversed to the control level following removal of the clip. In contrast, the expression of AQP2 channels as well as the activity of adenylyl cyclase remained unaltered in the contralateral kidney. These results indicate an altered regulation of AQP2 water channels in the clipped kidney in 2K1C hypertension.

Adenylyl Cyclases↗

Effects of BCG infection on Schultz-Dale reaction, allergen-specific IgE levels, and Th2 immune response in sensitized rats.

BACKGROUND: BCG, a potent inducer of Th1 immune response, has been suggested to suppress Th2 response which is known to mediate IgE-mediated allergic disorders, in particular allergic asthma. Schultz-Dale reaction is known to be a model of IgE-mediated hypersensitivity. This study was done to investigate whether BCG infection suppresses the Schultz-Dale reaction by inhibiting Th2 response and allergen-specific IgE production. METHODS: Twenty-four Sprague-Dawley rats were sensitized and provoked with ovalbumin (OVA). A pretreatment of 6 x 10(4) colony forming units of BCG or saline was done 7 days before sensitization. The Schultz-Dale reaction was represented as tracheal smooth muscle contractions to 50 micrograms/mL OVA challenge in vitro. Serum OVA-specific IgE levels and IFN-gamma and IL-4 concentrations in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: The Schultz-Dale reaction and serum OVA-specific IgE levels were significantly decreased in BCG infected and OVA sensitized rats compared with only sensitized rats (p < 0.01 and p < 0.05, respectively). As compared with only sensitized rats, IL-4 concentration and a ratio of IFN-gamma:IL-4 in BCG infected and OVA sensitized rats were significantly decreased (p < 0.001) and increased (p < 0.05), respectively. The Schultz-Dale reaction was correlated with OVA-specific IgE levels (r = 0.50, p < 0.05), IL-4 concentration (r = 0.69, p < 0.001), and ratio of IFN-:IL-4 (r = -0.44, p < 0.05). OVA-specific IgE levels were correlated with IL-4 concentration (r = 0.61, p < 0.01) and ratio of IFN-gamma:IL-4 (r = -0.48, p < 0.05). CONCLUSION: These findings suggest that BCG infection prior to allergen sensitization may inhibit Schultz-Dale reaction developed in the sensitized rat tracheal smooth muscle via the suppressive effects of Th2 immune response and allergen-specific IgE production.

Animals↗

Total occlusion of left main coronary artery by dilated main pulmonary artery in a patient with severe pulmonary hypertension.

A 34-year-old woman was admitted to the hospital because of recently aggravated right heart failure without angina for 5 months. When she was 25 years old, patch repair with Polytetrafluoroethylene (PTFE) was performed for the secondum type of atrial septal defect (ASD) with moderate pulmonary hypertension. The chest PA, echocardiography and cardiac catheterization at current admission revealed Eisenmenger syndrome without intracardiac shunt. Chest CT scan with contrast revealed markedly dilated pulmonary trunk, both pulmonary arteries and concave disfigurement of the left side of the ascending aorta suggesting extrinsic compression, as well as total occlusion of the ostium of the left main coronary artery that was retrogradly filled with collateral circulation from the right coronary artery. The coronary angiography showed normal right coronary artery and the collaterals that come out from the conus branch to the mid-left anterior descending artery (LAD) and that from distal right coronary artery to the left circumflex artery (LCX) and to the distal LAD, respectively. On aortography, the left main coronary artery was not visualized with no stump, suggestive of total occlusion of the ostium of the left main coronary artery. From our experience, it is possible to say that the occlusion of the ostium of the left main coronary can be induced by the dilated pulmonary artery trunk due to ASD with pulmonary hypertension and that, if the ASD closure was too late, the narrowing or obstruction of the left coronary artery could not be resolved even after operation owing to irreversible pulmonary hypertension.

Adult↗

Transformation by H-ras can result in aberrant regulation of ornithine decarboxylase gene expression by transforming growth factor-beta(1).

Inhibition of DNA synthesis and cell proliferation is frequently lost during malignant transformation and occasionally, tumour cell proliferation is actually stimulated by transforming growth factor beta(1) (TGF-beta(1)). The present study demonstrates a novel link between alterations in TGF-beta(1) regulation during cellular transformation and malignant conversion and the expression of ornithine decarboxylase (ODC) which is a key rate limiting activity in the biosynthesis of polyamines and which is an enzyme that plays an important role in cell growth and differentiation. H-ras transformed mouse 10T(1/2) cell lines of varying degrees of malignant potential were examined for possible TGF-beta(1)-mediated alterations in ODC expression. Selective induction of ODC gene expression occurred. This induction was dependent upon the cellular phenotype expressed and the mechanisms responsible for the regulation of the TGF-beta(1)-mediated alterations in ODC expression varied as a function of malignant potential. The TGF-beta(1)-mediated alterations in ODC gene expression involves de novo protein synthesis, transcriptional, and post-transcriptional events. Evidence is also presented to suggest a possible role for protein kinase C-mediated events, protein phosphatases, and G-protein-coupled events in the TGF-beta(1)-mediated regulation of ODC expression in H-ras transformed cells. Evidence is also presented to suggest a possible role for cellular polyamines in the TGF-beta(1)-mediated alterations in ODC expression in H-ras transformed cells. Additionally, alterations in cellular polyamines were shown to influence TGF-beta(1) gene expression in H-ras transformed cells and that these alterations occurred, in part, through post-transcriptional events. The TGF-beta(1)-mediated regulation of ODC expression in H-ras transformed cells of varying degrees of malignant potential appears to be complex, multifaceted, and interactive. This study illustrates the importance of TGF-beta(1)-mediated regulation of ODC expression as a result of H-ras mediated cellular transformation and malignant progression, and further suggests that this TGF-beta(1)-mediated regulation constitutes an integral part of an altered growth regulatory program.

Animals↗

Tumour promoter mediated altered expression and regulation of ornithine decarboxylase and S-adenosylmethionine decarboxylase in H-ras-transformed fibrosarcoma cell lines.

Alterations in cellular growth are important in the progression of malignant disease. Cell growth regulation by tumour promoters can be complex. The present study demonstrates a novel link between alterations in phorbol ester tumour promoter mediated regulation during malignant conversion and the expression of ornithine decarboxylase and S-adenosylmethionine decarboxylase, key rate-limiting and regulatory activities in the biosynthesis of polyamines. H-ras-transformed mouse 10 T 1/2 cell lines exhibiting increasing malignant potential were investigated for possible phorbol ester tumour promoter mediated changes in ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) gene expression. Selective induction of ODC and SAMDC gene expression was observed, since in contrast to nontransformed parental 10 T1/2 cells, ras-transformed cells capable of benign tumour formation (NR3 cells) and ras-transformed cells capable of metastasis formation (C2 cells) exhibited marked alterations in the levels of ODC and SAMDC gene expression. Increased ODC gene and SAMDC gene expression in response to phorbol-12-myristate-13-acetate (PMA) treatment was found to involve transcriptional events in both NR3 cells and in C2 cells. Post-transcriptional events also played a role in the regulation of ODC gene expression in NR3 cells and in C2 cells, and in the regulation of SAMDC gene expression in C2 cells but not in NR3 cells. In NR3 cells, alterations in ODC and in SAMDC gene expression was an event requiring de novo protein synthesis, whereas in highly malignant C2 cells, protein synthesis inhibition following cycloheximide treatment in cooperation with PMA resulted in an augmentation of both ODC and SAMDC gene expression. Evidence is presented to suggest that the PMA-mediated alterations in ODC and in SAMDC gene expression in NR3 cells and in C2 cells involved protein kinase C - mediated events. The status of the cellular polyamine levels was also an important determinant of the PMA-mediated alterations that occurred in ODC and in SAMDC expression in these H-ras transformed cells. Collectively, these results suggest that PMA can modulate ODC and SAMDC expression in H-ras transformed cells and that the mechanisms involved in the PMA- mediated regulation of ODC and SAMDC gene expression changes as a function of H-ras mediated cellular transformation and malignant progression. This study further suggests a mechanism of PMA stimulation of transformed cells wherein early alterations in the regulatory control of ODC and SAMDC gene expression are important and critical.

Adenosylmethionine Decarboxylase↗

Development of virtual environment for treating acrophobia.

Virtual Reality (VR) is a new technology that makes humans communicate with computer. It allows the user to see, hear, feel and interact in a three-dimensional virtual world created graphically. Virtual Reality Therapy (VRT), based on this sophisticated technology, has been recently used in the treatment of subjects diagnosed with acrophobia, a disorder that is characterized by marked anxiety upon exposure to heights, avoidance of heights, and a resulting interference in functioning. Conventional virtual reality system for the treatment of acrophobia has a limitation in scope that it is based on over-costly devices or somewhat unrealistic graphic scene. The goal of this study was to develop a inexpensive and more realistic virtual environment for the exposure therapy of acrophobia. We constructed two types virtual environment. One is constituted a bungee-jump tower in the middle of a city. It includes the open lift surrounded by props beside tower that allowed the patient to feel sense of heights. Another is composed of diving boards which have various heights. It provides a view of a lower diving board and people swimming in the pool to serve the patient stimuli upon exposure to heights.

Altitude↗

A descriptive analysis of the use and cost of new-generation antihistamines in the treatment of allergic rhinitis: a retrospective database analysis.

OBJECTIVE: This retrospective database analysis was conducted to evaluate the use and cost of new-generation antihistamines (i.e., those that are nonsedating) in the treatment of allergic rhinitis in a managed care population. STUDY DESIGN: The study is a retrospective database review of medical and pharmacy-related claims linked by episodes of care. METHODS: Patients who had been diagnosed as having allergic rhinitis and had at least 1 prescription claim were identified from a database containing patient-level medical and pharmacy-related claims. The treatment patterns of patients with allergic rhinitis who met the study criteria were documented for a 12-month period in which the use of nonsedating antihistamines was described and the associated costs of various medications were assessed. Subanalyses of patients categorized by comorbidity status were also performed. RESULTS: A total of 202,426 patients participated in the study. Nonsedating antihistamines were used by 71% of the patients; the most commonly prescribed drugs were loratadine and fexofenadine. The mean annual charges per patient for the treatment of allergic rhinitis in the study population were $465.21 (standard deviation [SD], 548). The greatest departmental cost was that of pharmacy-related charges (mean, $236.02; SD, 233); the next highest cost was that of outpatient charges (mean, $216.31; SD, 396). Comparisons of departmental charges indicated the use of loratadine was associated with significantly higher treatment costs than that of fexofenadine in a number of patient subgroups. CONCLUSION: In this analysis, loratadine was associated with significantly higher treatment charges than was fexofenadine. This result was observed consistently across different stratifications of patients, including the presence of comorbid respiratory infection, concomitant use of nasal steroids, and the presence of asthma and/or sinusitis. These results provided useful insights into the differential costs associated with the use of nonsedating antihistamines in the treatment of rhinitis.

Adolescent↗

The metabolism of fatty acids in human Bietti crystalline dystrophy.

PURPOSE: To investigate the role of abnormal lipid metabolism in Bietti crystalline dystrophy. METHODS: Cultured human lymphocytes and fibroblasts from patients with Bietti crystalline dystrophy (BCD) were incubated in the presence of [(14)C]18:3n-3 or [(14)C]18:2n-6. Incorporation into the cellular lipid pools and further metabolism by desaturation or elongation were monitored by thin-layer chromatography and HPLC. Results were compared with those in normal control subjects and patients with Wolman disease (WD). RESULTS: Pulse-chase experiments with labeled fatty acids in all groups showed that, after 1 hour, radioactivity was largely confined to the triacylglyceride (TG) and choline phosphoglyceride (CPG) pools. However, after several hours, radioactivity was transferred from the TG and CPG pools, some going to the serine and ethanolamine phosphoglyceride (SPG and EPG) pools. Fibroblasts from all groups showed direct transfer of fatty acids (FAs) into CPG and EPG. Incorporation of labeled FAs into the EPG pool paralleled extensive desaturation and elongation of 18:2n-6 to 22:5n-6 and 18:3n-3 to 22:6n-3. Fibroblasts from patients with WD (a lysosomal acid lipase deficiency characterized by excessive lipid accumulation), showed higher incorporation of 18:2n-6 into TGs than did normal or BCD fibroblasts. Conversely, fibroblasts from patients with BCD showed lower conversion of 18:3n-3, but not of 18:2n-6, into polyunsaturated FAs (PUFAs) than those of normal subjects or patients with WD. This was true for total FAs, CPGs, and EPGs. Similar results were found in both fibroblasts and lymphocytes; however, unlike fibroblasts, lymphocytes from normal subjects showed similar levels of incorporation of FAs into EPGs and CPGs. In contrast, incorporation of 18:3n-3 into EPGs was decreased in lymphocytes from patients with BCD. CONCLUSIONS: BCD is characterized by a lower than normal conversion of FA precursors into n-3 PUFA, whereas there is a higher than normal level of n-6 and n-3 FAs incorporation into TGs in cells from patients with WD. These findings raise the possibility that abnormal lipid metabolism associated with BCD is the result of deficient lipid binding, elongation, or desaturation in contrast to the lysosomal acid lipase deficiency found in Wolman disease.

Cells, Cultured↗

Chronic necrotizing pulmonary aspergillosis. A report of 9 cases with analysis of clinical picture, risk factors and treatment for outcome correlation.

Nine patients with chronic necrotizing pulmonary aspergillosis (CNPA) were analyzed retrospectively. Eight cases had been treated with itraconazole. Four patients had received intravenous amphotericin B (AMB), three sequentially with itraconazole and one as monotherapy. Three patients died after 1, 2 and 24 weeks of therapy. Six responded to therapy and survived 3 to 58 months after treatment. Only the total number of risk factors was found to be statistically significant in relation to a fatal outcome. The mean number of risk factors was 5.33 for fatal cases compared to 2.83 for treatment responders. The presence of five or more risk factors and two individual risk factors, hypoalbuminemia less than 27 g/L and history of dual pulmonary mycobacterioses, were 100% predictive of mortality in our patients. The overall clinical picture of fatal CNPA cases resembles closely that of acute invasive pulmonary aspergillosis in severely immunocompromised subjects.

Aged↗

Accuracy of three-dimensional quantification of left ventricular function using magnetic sensor acquisition: a dynamic in vitro model.

OBJECTIVE: To evaluate the accuracy of a three-dimensional (3D) magnetic position sensor system in the quantification of ventricular stroke volumes in a dynamic model. METHODS: A latex balloon model of the left ventricle was suspended in a water bath connected to a pump producing 10 different pulsatile stroke volumes (15-65 ml/beat). Scanning was performed using a 5.0 mHz transducer mounted with a Flock of Birds (FOB) magnetic receiver (GE System Five). The probe was scanned to sweep continuously across and over the balloon volume over 3-7 seconds. Digital loops were stored on magneto-optical disks and reviewed retrospectively using 3D Echopac software (GE) based on Simpson's method and compared with a two-dimensional (2D) biplane area-length method (1/2 L x R) measurements at end systole and end diastole. Both 3D and 2D derived stroke volumes were compared with the reference stroke volume calculated by direct measurement of balloon capacity. RESULTS: There was an improved correlation between 3D stroke volume and reference stroke volume (y = 0.91x + 0.41, r = 0.97, SEE = 2.83 ml, P = 0.0001) compared to 2D stroke volume and reference stroke volume (y = 0.49x + 8.68, r = 0.87, SEE = 3.87 ml, P = 0.0011, difference between 2D and 3D P < 0.003). CONCLUSION: 3D magnetic FOB scanning is practical, accurate and should facilitate assessment of left ventricular function.

Echocardiography, Three-Dimensional↗

A Web-based interactive education programme on vaccination for public health officials.

Health and Welfare Training Center of Korean National Institute of Health (KNIH) has developed various education curricula for officials who are involved in the public health or welfare sectors. Still almost all education programmes are off-line based. In off-line settings, both the lecturers and the students should come to NIH from their counties to join the education programmes, and it is impossible for the students to review or to re-practice the education contents. We developed a prototype on-line setting education programmes to provide a more convenient and more effective service to the officials. This web-based interactive education programme consisted of the specific objectives on vaccination for the public health officials who were working for the national immunization programmes. It became a prototype of web-based education and was evaluated by the participants in April, 2001. From the evaluation, we improved the contents and tried to develop more subjects for the officials' training.

Adult↗

Toxicity and Efficacy of Concurrent Gemcitabine and Radiotherapy for Locally Advanced Pancreatic Cancer.

Gemcitabine has been demonstrated to be a potentradiosensitizer in the laboratory and in the clinic (1-7)and has proven clinical systemic activity to pancreaticcancer. Responses to systemic gemcitabine inpatients with metastatic pancreatic adenocarcinomahave been documented in phase I, phase II, and phaseIII clinical settings (8,9). Moreover, a recent randomizedtrial of gemcitabine vs 5-FU as first-linetherapy in patients with advanced pancreatic adenocarcinomademonstrated a modest median survivalbenefit (4.41 vs 5.65 mo,p= 0.0025) for those patientswho received gemcitabine compared to those whoreceived 5-FU (10). In addition, gemcitabine wasshown to improve cancer-related symptoms and performancestatus as assessed by a quantitative clinicalbenefit scale in both untreated and previouslytreated patients with metastatic adenocarcinoma ofthe pancreas (10,11). Based on these data, the FDAapproved gemcitabine as a first-line agent for patientswith advanced adenocarcinoma of the pancreas.

Journal Article↗

Blockade of p38 mitogen-activated protein kinase pathway inhibits interleukin-6 release and expression in primary neonatal cardiomyocytes.

The induction of interleukin-6 (IL-6) using combined proinflammatory agents (LPS/IFN-gamma or TNF-alpha/IFN-gamma) was studied in relation to p38 mitogen-activated protein kinase (MAPK) and NF-kappaB transcriptional factor in primary neonatal cardiomyocytes. When added to cultures of cardiomyocytes, the combined agents (LPS/IFN-gamma or TNF-alpha/IFN-gamma) had stimulatory effect on the production of IL-6 and the elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. SB203580 inhibited protein production and gene expression of IL-6 in a concentration-dependent manner. In this study, IFN-gamma enhancement of TNF-alpha-induced NF-kappaB binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha/IFN-gamma or LPS/IFN-gamma-induced NF-kappaB activation. This study strongly suggests that these pathways about TNF-alpha/IFN-gamma or LPS/IFN-gamma-activated IL-6 release can be primarily dissociated in primary neonatal cardiomyocytes.

Animals↗

Proteome analysis of light-induced proteins in Synechocystis sp. PCC 6803: identification of proteins separated by 2D-PAGE using N-terminal sequencing and MALDI-TOF MS.

The cyanobacterium Synechocystis sp. PCC 6803 is an ideal model organism for the proteome study of light-induced gene expression because the whole genomic sequence has been determined. The soluble proteins extracted from light- and dark-cultured cells were separated by two-dimensional polyacrylamide gel electrophoresis. Light-induced protein spots electroblotted on a polyvinyldiene difluoride membrane were analyzed by N-terminal Edman sequence determination and followed by CyanoBase. The tryptic digests of some proteins were also confirmed by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) and MS-Fit search. Interestingly, eight proteins were related to photosynthesis and respiration (RbcS/L, CbbA, Gap2, AtpB, CpcB, PsbO, and PsbU). Four proteins (SodB, DnaK, GroEL2, and Tig) were involved in cellular processes and the functions of another two proteins (rehydrin and membrane protein) were unknown. The proteome analysis by N-terminal Edman sequencing and MALDI-TOF enabled us to characterize one-shot protein profiles expressed under different physiological conditions.

Amino Acid Sequence↗

Two isoforms of sarco/endoplasmic reticulum calcium ATPase (SERCA) are essential in Caenorhabditis elegans.

SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase), a membrane bound Ca(2+)- /Mg(2+)- dependent ATPase that sequesters Ca(2+) into the SR/ER lumen, is one of the essential components for the maintenance of intracellular Ca(2+) homeostasis. Here we describe the identification and functional characterization of a C. elegans SERCA gene (ser-1). ser-1 is a single gene alternatively spliced at its carboxyl terminus to form two isoforms (SER-1A and SER-1B) and displays a high homology (70% identity, 80% similarity) with mammalian SERCAs. Green fluorescent protein (GFP) and whole-mount immunostaining analyses reveal that SER-1 expresses in neuronal cells, body-wall muscles, pharyngeal and vulval muscles, excretory cells, and vulva epithelial cells. Furthermore, SER-1::GFP expresses during embryonic stages and the expression is maintained through the adult stages. Double-stranded RNA injection (also known as RNAi) targeted to each SER-1 isoform results in severe phenotypic defects: ser-1A(RNAi) animals show embryonic lethality, whereas ser-1B(RNAi) results in L1 larval arrest phenotype. These findings suggest that both isoforms of C. elegans SERCA, like in mammals, are essential for embryonic development and post-embryonic growth and survival.

Alternative Splicing↗