Search PubMed⌕ Search

Biomedical subjects

K Choi

Publications and source records attributed to K Choi.

At least 73 records · Page 4Linked to original sources

Antigen recognition properties of mutant V beta 3+ T cell receptors are consistent with an immunoglobulin-like structure for the receptor.

We examined the effect of mutations in the V beta portion of a pigeon cytochrome c (cyto c)-specific V beta 3+/V alpha 11+ T cell receptor on its ability to recognize cyto c/IEk and various superantigens. The results were consistent with an immunoglobulin-like structure for the receptor V beta domain and with separate interaction sites on V beta for conventional antigen and superantigens. An amino acid predicted to lie in CDR1 was critical for cyto c/IEk but not superantigen recognition, while several amino acids predicted to lie in the hypervariable region 4 loop were critical for superantigen but not cyto c/IEk recognition.

Amino Acid Sequence↗

A comparison of the fatigue behavior of human trabecular and cortical bone tissue.

The fatigue properties of trabecular bone tissue (single trabeculae) and similarly sized cortical bone specimens from human tibia were experimentally determined on a microstructural level using four-point bending cyclic tests, and they were compared based on modulus, mineral density, and microstructural characteristics. The results showed that trabecular specimens had significantly lower moduli and lower fatigue strength than cortical specimens, despite their higher mineral density values. Fracture surface and microdamage analyses illustrated different fracture and damage patterns between trabecular and cortical bone tissue, depending upon their microstructural characteristics. Based on the results from mechanical tests and qualitative observations, a possible mechanical role of the cement lines in trabecular tissue microfracture was suggested.

Bone Density↗

Multidrug resistance after retroviral transfer of the human MDR1 gene correlates with P-glycoprotein density in the plasma membrane and is not affected by cytotoxic selection.

Multidrug resistance (MDR) in mammalian cells is associated with the expression of the MDR1 gene encoding P-glycoprotein (P-gp), an and active efflux pump for various lipophilic compounds. MDR transfectants can be isolated after MDR1 gene transfer and selection with cytotoxic drugs; low levels of drug resistance have also been observed in unselected NIH 3T3 mouse cells after retrovirus-mediated transfer of mouse mdr1 cDNA. MDR cell lines possess multiple phenotypic changes, suggesting that P-gp function could be complemented by some additional mechanisms associated with cytotoxic selection. To determine whether cytotoxic selection contributes to the MDR phenotype of MDR1-expressing cells, NIH 3T3 cells infected with a recombinant retrovirus carrying the human MDR1 gene were selected by two different procedures: (i) noncytotoxic selection for increased P-gp expression on the cell surface by multiple rounds of immunofluorescence labeling and flow sorting or (ii) one or more steps of selection with a cytotoxic drug. The levels of MDR in both types of infectants showed an excellent correlation with the P-gp density in the plasma membrane, expressed as immunoreactivity with a P-gp-specific antibody normalized by reactivity with an antibody against an unrelated antigen. Cytotoxic selection conferred no additional increase in resistance relative to P-gp density. These results indicate that P-gp density in the plasma membrane may be sufficient to determine the level of MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A breast cancer screening program in a community hospital.

Breast cancer screening continues to be underutilized in the United States. The National Cancer Institute has set a goal of increasing screening by the year 2000. The American Cancer Society wants to identify programs that target asymptomatic women and economically disadvantaged women. The purpose of this study was to develop, implement and evaluate a comprehensive breast cancer screening program for women in a community setting. One case of infiltrating ductal carcinoma was detected from the 144 women who participated in the study. Following the educational component, the post test demonstrated a significant increase (p less than 0.01) in the women's awareness of breast cancer. Additionally, 100% of the women were able to demonstrate breast self examination to an oncology nurse after the educational component of the study. The majority of the women who participated were not economically disadvantaged which sheds new light on the scope of the problem of taking care of the unmet cancer needs of the disadvantaged through outreach programs. However 27% of the women had a household income less than $10,000 with 19% of the women having no insurance and 7% having Medicare/Medicaid. The results of this study could help future programs in bringing breast cancer screening to women in the community setting.

Adult↗

APACHE II: prediction of outcome of 451 ICU oncology admissions in a community hospital.

The APACHE II system has been shown to be a reliable and useful means of evaluating patient outcome from the intensive care unit when applied to a broad spectrum of diagnoses. The major purpose of this study was to determine the use of APACHE II as a means of predicting outcome of ICU oncology patients. Data were retrospectively collected for 451 ICU oncology admissions. A direct relationship between severity of physiologic derangement and patient risk of death was demonstrated. Patients with scores of 30 or greater had hospital mortality rates of 100% for postoperative and 92.6% for nonoperative patients. The APACHE II was a useful means of predicting the outcome of ICU oncology patients. This potentially provides the patient, family, and physician an objective dimension in making decisions whether to transfer the oncology patient.

Adolescent↗

The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus.

The elastic moduli of human subchondral, trabecular, and cortical bone tissue from a proximal tibia were experimentally determined using three-point bending tests on a microstructural level. The mean modulus of subchondral specimens was 1.15 GPa, and those of trabecular and cortical specimens was 4.59 GPa and 5.44 GPa respectively. Significant differences were found in the modulus values between bone tissues, which may have mainly resulted from the differences in the microstructures of each bone tissue rather than in the mineral density. Furthermore, the size-dependency of the modulus was examined using eight different sizes of cortical specimens (heights h = 100-1000 microns). While the modulus values for relatively large specimens (h greater than 500 microns) remained fairly constant (approximately 15 GPa), the values decreased as the specimens became smaller. A significant correlation was found between the modulus and specimen size. The surface area to volume ratio proved to be a key variable to explain the size-dependency.

Bone Density↗

Prophylactic irradiation of the para-aortic lymph node chain in stage IIB and bulky stage IB carcinoma of the cervix, initial treatment results of RTOG 7920.

From November 1979 to October 1986, 367 patients were entered onto RTOG 7920 and randomized to receive either pelvic irradiation alone or pelvic plus para-aortic radiation. Patients with Stage IIB cervical carcinoma who had not undergone curative surgery and patients with Stages IB and IIA cervical carcinoma who were determined by digital exam to have primary tumors measuring 4 cm or greater in lateral dimension were eligible for this study. Clinically apparent or surgically involved para-aortic nodes were reason for exclusion from the study. Pelvic irradiation consisted of 1.6-1.8 Gy per day for 5 days per week to a total of 40-50 Gy. Para-aortic irradiation delivered 44 to 45 Gy in 1.6-1.8 Gy per day, 5 days per week. Pelvic irradiation was to be completed in 4 1/2 to 6 1/2 weeks and para-aortic irradiation in 4 1/2 to 5 1/2 weeks. Intracavitary brachytherapy delivered a total of 4000-5000 mg hr of radium-equivalents or 30-40 Gy to point A. Patients were stratified prior to random treatment assignment by histology, para-aortic nodal status (negative vs. unevaluated), and FIGO stage. As of June 1, 1989, 30 cases were excluded, including five patients who were inevaluable. Two patients who refused the assigned treatment were also excluded. Therefore, a total of 330 cases were analyzable. At 5 years the estimates of survival, the primary endpoint, for the pelvic only and pelvic plus para-aortic irradiation arms are 55% and 65%, respectively (p = 0.043). Several secondary endpoints were also analyzed. Estimates for loco-regional control at 5 years are, for pelvic irradiation only, 66%, and for pelvic plus para-aortic irradiation, 75% (p = 0.21). Distant metastases are estimated in 32% of pelvic irradiation only patients and 25% of pelvic plus para-aortic irradiation patients at 5 years (p = 0.17). When the first disease failure patterns are examined, more patients fail distally when treated only with pelvic radiation than when using pelvic plus para-aortic fields (p = .04). In analysis of patients with grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal complications), 8% of the patients in both groups had grade 3 severe complications. In the pelvic plus para-aortic group, 11 patients had grade 4 and 2 had grade 5 complications, whereas 6 had grade 4 and none had grade 5 in the pelvic only treatment group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Molecular basis of preferential resistance to colchicine in multidrug-resistant human cells conferred by Gly-185----Val-185 substitution in P-glycoprotein.

Expression of P-glycoprotein, encoded by the human MDR1 gene, results in cross-resistance to many lipophilic cytotoxic drugs (multidrug resistance). P-glycoprotein is believed to function as an energy-dependent efflux pump that is responsible for decreased drug accumulation in multidrug-resistant cells. Previous work showed that preferential resistance to colchicine in a colchicine-selected multidrug-resistant cell line was caused by spontaneous mutations in the MDR1 gene that resulted in a Gly-185----Val-185 substitution in P-glycoprotein. We have now compared transfectant cell lines expressing either the wild-type Gly-185 or the mutant Val-185 P-glycoprotein with regard to their levels of resistance to and accumulation and binding of different drugs. In cells expressing the mutant protein, increased resistance to colchicine and decreased resistance to vinblastine correlated with a decreased accumulation of colchicine and increased accumulation of vinblastine. Expression of the mutant P-glycoprotein also resulted in significantly increased resistance to epipodophyllotoxin and decreased resistance to vincristine and actinomycin D; smaller changes in resistance were observed for several other drugs. Unexpectedly, the mutant P-glycoprotein showed increased binding of photoactive analogs of vinblastine and verapamil and the photoactive compound azidopine and decreased binding of a photoactive colchicine analog. These results suggest that the Gly-185----Val-185 substitution affects not the initial drug-binding site of P-glycoprotein but another site, associated with the release of P-glycoprotein-bound drugs to the outside of the cell.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Diminished survival of young blacks with adenocarcinoma of the prostate.

The survival rates of 117 black and white patients treated by primary radiation for carcinoma of the prostate at the State University of New York Health Science Center at Brooklyn and Kings County Hospital Center were analyzed according to age and race. In addition, stage, grade, and delay time in seeking medical attention were analyzed. Survival was similar in both young (less than 60 years) and old (greater than or equal to 60 years) patients, with 45% and 41% 5-year-survival rates, respectively. Survival was better in white patients, 48% 5-year survival, than in blacks, 35% 5-year survival. Black patients presented with higher stage disease than whites (p less than 0.01). This trend was even greater in young black males, who had higher grade (64% versus 11%; p less than 0.04) and higher stage tumors (p less than 0.05). In addition, young blacks delayed seeking medical attention greater than 3 months 72% of the time, as compared to 0% in white young males (p less than 0.005). A survival difference was also seen in young blacks as compared with young whites: 3.9-year median survival versus 6.0-year median survival, respectively.

Black or African American↗

Comparison of the trabecular and cortical tissue moduli from human iliac crests.

The purpose of this study was to design a method to produce and test mechanically microspecimens of trabecular and cortical tissue from human iliac crests, and compare their measured moduli. Rectangular beam specimens were prepared on a low-speed diamond blade saw and a miniature milling machine. The final specimen dimensions ranged from approximately 50-200 microns for base and height. The modulus of each specimen was measured using three-point bending tests across a span length of 1.04 mm and performed at a constant rate of displacement. A subset of specimens was recovered for a radiographic estimation of degree of mineralization. The results showed the mean trabecular tissue modulus of all iliac crest specimens to be 3.81 GPa, whereas cortical tissue specimens averaged 4.89 GPa. This was a significant difference according to a two-way analysis of variance that controlled for differences between donors. No strong correlations were found between modulus and mineral density. Future investigations that consider other microstructural characteristics and their contributions to modulus, and specimen size effects, are indicated.

Bone and Bones↗

Structure and expression of the human MDR (P-glycoprotein) gene family.

The human MDR (P-glycoprotein) gene family is known to include two members, MDR1 and MDR2. The product of the MDR1 gene, which is responsible for resistance to different cytotoxic drugs (multidrug resistance), appears to serve as an energy-dependent efflux pump for various lipophilic compounds. The function of the MDR2 gene remains unknown. We have examined the structure of the human MDR gene family by Southern hybridization of DNA from different multidrug-resistant cell lines with subfragments of MDR1 cDNA and by cloning and sequencing of genomic fragments. We have found no evidence for any other cross-hybridizing MDR genes. The sequence of two exons of the MDR2 gene was determined from genomic clones. Hybridization with single-exon probes showed that the human MDR1 gene is closely related to two genes in mouse and hamster DNA, whereas MDR2 corresponds to one rodent gene. The human MDR locus was mapped by field-inversion gel electrophoresis, and both MDR genes were found to be linked within 330 kilobases. The expression patterns of the human MDR genes were examined by enzymatic amplification of cDNA. In multidrug-resistant cell lines, increased expression of MDR1 mRNA was paralleled by a smaller increase in the levels of MDR2 mRNA. In normal human tissues, MDR2 was coexpressed with MDR1 in the liver, kidney, adrenal gland, and spleen. MDR1 expression was also detected in colon, lung, stomach, esophagus, muscle, breast, and bladder.

ATP Binding Cassette Transporter, Subfamily B, Mem↗