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Biomedical subjects

O Lee

Publications and source records attributed to O Lee.

13 recordsLinked to original sources
PubMed1999

Human acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene organization and evidence that the 4.3-kilobase ACAT-1 mRNA is produced from two different chromosomes.

Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis. Four human ACAT-1 mRNAs (7.0, 4.3, 3.6, and 2.8 kilobases (kb)) share the same short 5'-untranslated region (exon 1) and coding sequence (exons 2-15). The 4.3-kb mRNA contains an additional 5'-untranslated region (1289 nucleotides in length; exons Xa and Xb) immediately upstream from the exon 1 sequence. One ACAT-1 genomic DNA insert covers exons 1-16 and a promoter (the P1 promoter). A separate insert covers exon Xa (1277 base pairs) and a different promoter (the P7 promoter). Gene mapping shows that exons 1-16 and the P1 promoter sequences are located in chromosome 1, while exon Xa and the P7 promoter sequence are located in chromosome 7. RNase protection assays demonstrate three different protected fragments, corresponding to the 4.3-kb mRNA and the two other mRNAs transcribed from the two promoters. These results are consistent with the interpretation that the 4.3-kb mRNA is produced from two different chromosomes, by a novel RNA recombination mechanism involving trans-splicing of two discontinuous precursor RNAs.

5' Untranslated Regions↗
PubMed1998

Expression of ACAT-1 protein in human atherosclerotic lesions and cultured human monocytes-macrophages.

The acyl coenzyme A:cholesterol acyltransferase (ACAT) gene was first cloned in 1993 (Chang et al, J Biol Chem. 1993;268:20747-20755; designated ACAT-1). Using affinity-purified antibodies raised against the N-terminal portion of human ACAT-1 protein, we performed immunohistochemical localization studies and showed that the ACAT-1 protein was highly expressed in atherosclerotic lesions of the human aorta. We also performed cell-specific localization studies using double immunostaining and showed that ACAT-1 was predominantly expressed in macrophages but not in smooth muscle cells. We then used a cell culture system in vitro to monitor the ACAT-1 expression in differentiating monocytes-macrophages. The ACAT-1 protein content increased by up to 10-fold when monocytes spontaneously differentiated into macrophages. This increase occurred within the first 2 days of culturing the monocytes and reached a plateau level within 4 days of culturing, indicating that the increase in ACAT-1 protein content is an early event during the monocyte differentiation process. The ACAT-1 protein expressed in the differentiating monocytes-macrophages was shown to be active by enzyme assay in vitro. The high levels of ACAT-1 present in macrophages maintained in culture can explain the high ACAT-1 contents found in atherosclerotic lesions. Our results thus support the idea that ACAT-1 plays an important role in differentiating monocytes and in forming macrophage foam cells during the development of human atherosclerosis.

Adult↗
PubMed1998

Immunodepletion experiments suggest that acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) protein plays a major catalytic role in adult human liver, adrenal gland, macrophages, and kidney, but not in intestines.

The first acyl-coenzyme A:cholesterol acyltransferase (ACAT) cDNA cloned and expressed in 1993 is designated as ACAT-1. In various human tissue homogenates, ACAT-1 protein is effectively solubilized with retention of enzymatic activity by the detergent CHAPS along with high salt. After using anti-ACAT-1 antibodies to quantitatively remove ACAT-1 protein from the solubilized enzyme, measuring the residual ACAT activity remaining in the immunodepleted supernatants allows us to assess the functional significance of ACAT-1 protein in various human tissues. The results showed that ACAT activity was immunodepleted 90% in liver (83% in hepatocytes), 98% in adrenal gland, 91% in macrophages, 80% in kidney, and 19% in intestines, suggesting that ACAT-1 protein plays a major catalytic role in all of the human tissue/cell homogenates examined except intestines. Intestinal ACAT activity is largely resistant to immunodepletion and is much more sensitive to inhibition by the ACAT inhibitor Dup 128 than liver ACAT activity.

Adolescent↗
PubMed1996

A comparison of mixed integer programming and fast simulated annealing for optimizing beam weights in radiation therapy.

Two competing methods for assigning intensities to radiation treatment beams were tested. One method was derived from mixed integer programming and the other was based on simulated annealing. The methods faced a common objective and identical constraints. The goal was to maximize the minimum tumor dose while keeping the dose in required fractions of normal organ volumes below a threshold for damage. The minimum tumor doses of the two methods were compared when all the dose-volume constraints were satisfied. A mixed integer linear program gave a minimum tumor dose that was at least 1.8 Gy higher than that given by simulated annealing in 7 of 19 trials. The difference was > or = 5.4 Gy in 4 of 19 trials. In no case was the mixed integer solution one fraction size (1.8 Gy) worse than that of simulated annealing. The better solution provided by the mixed integer program allows tumor dose to increase without violating the dose-volume limits of normal tissues.

Abdominal Neoplasms↗
PubMed1996

A generic genetic algorithm for generating beam weights.

A genetic algorithm for generating beam weights is described. The algorithm improves an objective measure of the dose distribution while respecting dose volume constraints placed on critical structures. The algorithm was used to select beam weights for treatment of abdominal tumors. Weights were selected for up to 36 beams. Dose volume limits were placed on normal organs and a dose inhomogeneity limit was placed on tumor. Volumes were represented as sets of several hundred discrete points. The algorithm searched for the beam weights that would make the minimum tumor dose as high as the constraints would allow. The results were checked using dose volume histograms with standard sized grids. Nineteen trials were created using six patient cases by changing the required field margin or allowed beam position in each case. The sampling of points was sufficiently dense to yield solutions that strictly satisfied the constraints when the prescribed dose was renormalized by a factor of less than 6%. The genetic algorithm supplied solutions in 49 min on average, and in a maximum time of 87 min. The randomized search does not guarantee optimality, but high tumor doses were obtained. An example is shown for which the solution of the genetic algorithm gave a minimum tumor dose 7 Gy higher than the solution given by a simulated annealing algorithm under the same set of constraints. The genetic algorithm can be generalized to admit nonlinear functions of the beam intensities in the objective or in the constraints. These can include tumor control and normal tissue complication probabilities. The genetic algorithm is an attractive procedure for assigning beam weights in multifield plans. It improves the dose distribution while respecting specified rules for tissue tolerance.

Abdominal Neoplasms↗
PubMed1994

Regulation of collagenase gene expression by IL-1 beta requires transcriptional and post-transcriptional mechanisms.

Interleukin-1 beta is believed to contribute to the pathophysiology of rheumatoid arthritis by activating collagenase gene expression. We have used a cell culture model of rabbit synovial fibroblasts to examine the molecular mechanisms of IL-1 beta-mediated collagenase gene expression. Stimulation of rabbit synovial fibroblasts with 10 ng/ml recombinant human IL-1 beta resulted in a 20-fold increase in collagenase mRNA by 12 h. Transient transfection studies using collagenase promoter-CAT constructs demonstrated that proximal sequences responded poorly to IL-1 beta, possibly due to insufficient activation of AP-1 by this cytokine. More distal sequences were required for IL-1 beta responsiveness, with a 4700 bp construct showing approximately 5-fold induction above control. To examine post-transcriptional mechanisms, transcript from a human collagenase cDNA was constitutively produced by the simian virus 40 early promoter. IL-1 beta stabilized the constitutively expressed human transcript. Furthermore, mutation of the ATTTA motifs in the 3' untranslated region of the human gene also stabilized the transcript. Finally, the rabbit collagenase 3' untranslated region destabilized a constitutively transcribed chloramphenicol acetyltransferase transcript. These data indicate that in addition to activating transcription, IL-1 beta increases collagenase transcript stability by reversing the destabilizing effects of sequences in the 3' untranslated region.

Animals↗
PubMed1994

Coexistent duodenal ulcer among patients with gastric carcinoma.

To examine the prevalence of coexistent duodenal ulcers among patients with gastric carcinoma in an otherwise intact stomach, we surveyed 604 endoscopically and pathologically diagnosed gastric carcinoma patients and thoroughly inspected their duodenums. Twenty-two (3.6%) of them had either active ulcers or scars in the duodenum. This prevalence was significantly less than that among 99 (16.4%) of 604 age- and gender-matched controls with endoscopically confirmed duodenal ulcers (P < 0.0001). Almost one-half of patients with coexistent cancer and duodenal ulcer experienced no change in abdominal symptoms when gastric cancer was diagnosed. Barium meal study appeared not to be sensitive enough to diagnose the coexistent ulcers. However, the nature of the lesions, including disease location, macroscopic appearance, chance of early cancer and metastasis, was no different in 22 patients with coexistent cancer and duodenal ulcer than in 582 patients with cancer alone. The present study suggests that although duodenal ulcer is unlikely to be a predisposing factor for gastric cancer, thorough screening by means of endoscopy is necessary in dyspepsic ulcer patients since duodenal ulcer and gastric cancer are not incompatible.

Aged↗
PubMed1989

IR vibrational CD in alanyl tripeptide: indication of a stable solution conformer.

Infrared vibrational CD (VCD) of a small peptide, L-alanyl-L-alanyl-L-alanine (Ala3), and a peptide model, N-acetyl-L-alanine-N'-methyl-amide (AAMA), in the 1550-1750-cm-1 region has been observed. The "coupled oscillator" VCD feature observed for Ala3 in the amide I region is interpreted in terms of a solution structure stabilized by the electrostatic interaction of the zwitterionic groups. No such interactions are possible in basic aqueous solution of Ala3 nor in AAMA in neutral solution. Thus, the coupled oscillator features are lost in the latter two cases, indicating the absence of a simple stabilized conformation.

Alanine↗
PubMed1973

Antibodies to herpesvirus nonvirion antigens in squamous carcinomas.

Serums from tumor-bearing patients, cured patients, and normal subjects were examined for antibodies to the separated complement-fixing reactive components of nonvirion antigens of herpesvirus type 1 and type 2. The occurrence of antibodies to the antigens was similar in serums from tumor-bearing patients and cured patients. Antibodies to the antigens were observed among 21 of 24 (87 percent) cervical cancer cases, 44 of 49 (90 percent) laryngeal cancer cases, 15 of 24 (62 percent) cases of squamous cell carcinomas of the head and neck excluding the larynx, 2 of 24 (8 percent) nonsquamous cell cancer cases, and 3 of 51 (6 percent) normal subjects. By contrast, no differences were found in the titers of neutralizing antibodies to the virus in serums from laryngeal cancer patients and controls. The observations support an etiologic role of herpesviruses in cervical cancer and in laryngeal cancer, and possibly other squamous cell cancers of the head and neck.

Age Factors↗
PubMedDate not supplied

Falls in the rehabilitation setting: incidence and characteristics.

A prospective six-month study was conducted to determine a high-risk index for medical rehabilitation patients who fall. Variables studied for all patients included demographics, medical conditions, associated symptoms, orthostatic blood pressure measurements, physical function, posture control, proprioception, use of physical restraints, and medications, A detailed examination of the fall events was also conducted. Of the 143 patients studied, 46 (32%) fell at least once, making a total of 84 falls. Impaired ability to follow directions, impaired judgment, impaired proprioception, presence of physical restraints, use of major tranquilizers, use of sedatives, and presence of psychiatric diagnosis were all individually associated with patients who fell. Males fell more than females. Logistic regression identified altered proprioception as the only major predictor of falling. Of those who fell, only 26% called for assistance prior to the fall. Sixty-eight percent of the falls were from wheelchairs. Importantly, no patients had serious injury or morbidity from the falls.

Accidental Falls↗