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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 595 records · Page 33Linked to original sources
PubMed1994

HHV-6 in AIDS.

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AIDS-Related Opportunistic Infections↗
PubMed1994

Predicting protein mutant energetics by self-consistent ensemble optimization.

In this paper we present a self-consistent ensemble optimization (SCEO) theory for efficient conformational search, which we have applied to predicting the effects of mutations on protein thermostability. This approach takes advantage of a statistical mechanical self-consistency condition to home in iteratively on the global minimum structure. We employ a fast potential of mean-force approximation to cut computation time to a few minutes for a typical protein mutation, with only linear time-dependence on the size of the prediction problem. Rather than seeking a single, static structure of minimum energy, the new method optimizes an ensemble of many conformations, seeking to predict the most likely ensemble for the native state at a desired temperature. Testing this approach with a simple physical model focusing entirely on steric interactions and side-chain rearrangement, we obtain robustly convergent prediction of core side-chain conformation, and of hydrophobic core mutations' effects on protein stability. Self-consistent ensemble optimization is superior to simulated annealing in its speed and convergence to the global minimum, and insensitive to starting conformation. In calculations on lambda repressor protein, structural predictions for an eight-residue molten-zone had side-chain r.m.s. error of 0.49 A for the wild-type protein. Evaluation of the method's mutant structure predictions should become possible, as structures of these mutant repressors are solved. Predicted energies for a series of nine hydrophobic core mutants correlated with measured free energies of unfolding with a coefficient of 0.82.

Amino Acid Sequence↗
PubMed1994

Purification and biochemical characterization of two major cytochrome P-450 isoforms induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in chick embryo liver.

Two cytochrome P-450 isoforms induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in chick embryo liver microsomes were purified. The P-450s exhibit catalytic selectivity either for arachidonic acid metabolism, particularly epoxygenation (P-450 TCDDAA, 55 kDa), or for aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin deethylase (7-EROD) (P-450 TCDDAHH, 54.5 kDa). Turnover numbers for arachidonic acid epoxygenation, AHH, and 7-EROD, respectively, were 24.2, 0.23, and 0.45 for TCDDAA and 0.57, 9.7, and 35.5 for TCDDAHH. Both P-450s were low spin, with carbon monoxide-binding peaks at 448 nm. Their N-terminal amino acid sequences showed 80% homology and contained the sequence: PXXXSATEXL, common to CYP1A P-450s but not others. Polyclonal antibodies to TCDDAA and TCDDAHH cross-reacted with both P-450s on Western blots and immunoinhibited all TCDD-induced liver microsomal arachidonic acid metabolism, AHH, and 7-EROD. Immunoquantitation using antibodies made monospecific by immunoadsorption against the heterologous P-450 showed that TCDDAA and TCDDAHH were coinduced in liver in equal amounts and accounted for all of the TCDD-induced P-450. Enzyme assays and Western blots also showed expression of both TCDDAA and TCDDAHH in kidney but only of TCDDAHH in heart, indicating that these P-450s can be independently regulated and selectively induced. On Western blots non-immunopurified anti-TCDDAA and anti-TCDDAHH antisera recognized rat and guinea pig CYP1A1 and CYP1A2. Immunopurified TCDDAA antiserum only recognized rat CYP1A2, indicating that TCDDAA is more closely related immunochemically to CYP1A2 than to CYP1A1. The evidence that pleotropic responses to Ah receptor ligands can include induction of a P-450 that can form biologically active products from the endogenous membrane lipid, arachidonic acid, suggests that organ- and cell-specific expression of TCDD-induced P-450s could affect responses to TCDD.

Amino Acid Sequence↗
PubMed1994

PR92 antigen in human prostate fluid: elevated levels in prostate cancer.

In this preliminary study, we report that an enzyme-linked immunofluorescence assay (EFLA) was developed for the determination of PR92 antigen in prostatic fluid, utilizing anti-PR92 monoclonal antibody. Fluid samples from 64 patients were assayed. PR92 antigen was expressed as unit per microgram (U/microgram) of prostatic fluid proteins. One hundred percent of men (7 out of 7) less than 50 years of age demonstrated concentrations less than 25 U/micrograms; 91% of men (10 out of 11) with documented carcinoma, and only 9.5% of men (2 out of 21) with benign prostatic hyperplasia, demonstrated concentrations above 230 U/micrograms. The mean concentration of PR92 antigen in prostatic fluid of a group of patients suspected of having prostate cancer (high-risk group; 227 +/- 42 U/micrograms) was significantly greater than that of those with benign prostatic hyperplasia (87 +/- 23 U/micrograms; P = 0.05). Further evaluation of this potential marker and of other antigens within the prostatic fluid is warranted.

Adult↗
PubMed1994

A tandemly repetitive, centromeric DNA sequence from the Canadian woodland caribou (Rangifer tarandus caribou): its conservation and evolution in several deer species.

A highly repetitive DNA clone, designated Rt-Pst3, was isolated from the PstI digest of Canadian woodland caribou (Rangifer tarandus caribou; 2n = 70) genomic DNA. It was found to be a 991 bp monomer of a tandemly repeated DNA sequence comprising about 5.7% of the genome and localized to the centromeric regions of all caribou acrocentric autosomes. Southern blot analyses revealed that this caribou satellite DNA sequence was well conserved in the genomes of five other deer species studied. In situ hybridization studies revealed Rt-Pst3-homologous DNA sequences in the centromeric regions of white-tailed deer chromosomes and Asian muntjac chromosomes, as well as at several interstitial chromosome regions in Indian muntjac chromosomes. Comparisons of the Rt-Pst3 DNA sequence to previously identified centromeric satellite DNA fragments from three other deer species revealed considerable DNA sequence similarity. The first ca. 800 bp of the Rt-Pst3 clone was found to share 73.8% similarity to the CCsatI clone of the European roe deer, 64.7% sequence similarity to the C5 DNA clone of the Chinese muntjac, and 64.8% and 65.6% sequence similarity to the 1A and B1 clones of the Indian muntjac, respectively. Moreover, the last 191 bp of the Rt-Pst3 clone was found to share about 60% DNA sequence similarity to the first 191 bp of the same clone. Amplification of one original ca. 800 bp monomer unit, along with the first 191 bp of the following juxtaposed monomer unit could have resulted in the tandemly repeated, 991 bp monomer unit now seen in the caribou genome. It is postulated that the centromeric satellite DNA found in other deer species, having repeat lengths greater than 800 bp, could also have evolved in a similar manner from a more ancestral monomeric unit of ca. 800 bp.

Animals↗
PubMed1994

Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung hemorrhage.

Exposure conditions were determined for hind limb paralysis and lung hemorrhage of neonatal mice due to pulsed exposure (10 microsecond pulse duration) to 1 MHz focused ultrasound. Spatial peak pulse average intensity and peak rarefactional pressure levels for paralysis in 50% of specimens sonicated were determined for pulse repetition frequencies of 1, 5 and 50 kHz at 10 degrees C and 2.4 s exposure duration. The results suggest that cavitation was involved in the paralysis at a pulse repetition frequency (PRF) of 50 kHz, but that cavitation took place in the coupling medium and probably not within the specimen during exposures at a PRF of 5 kHz. The results show an inverse relation between spatial peak pulse average intensity, or peak rarefactional pressure and sound on-time. Exposure conditions for lung hemorrhage were determined for a pulse duration of 10 microseconds at 10 degrees C and exposure durations of 2.4 and 180 s. The results show that the threshold exposure conditions for lung hemorrhage are much less than the conditions for cavitational or other effects reported for tissues that do not contain well defined gas bodies. In addition, the results show an inverse relation between exposure level and either exposure duration or sound on-time, suggesting that time is an important parameter associated with bubble effects.

Animals↗
PubMed1994

ED length-of-stay and illness severity in dizzy and chest-pain patients.

Emergency department (ED) length of stay, illness severity, and patterns of ED-based testing can be used to compare different ED patient populations. To assess the relative significance of ED patients with dizziness and chest pain in emergency medicine practice, the investigators formed a retrospective chart review of 3,864 adults (age > or = 16 years) seen at the University of North Carolina Hospitals' ED during May and June of 1991. Patients were eligible if they had any complaint of dizziness (n = 259), nontraumatic chest pain (n = 168), or both (n = 18). ED length of stay and illness severity, as measured by Acute Physiology and Chronic Health Evaluation (APACHE) II score, were not significantly different between the two groups. Dizzy and chest-pain patients were both high users of ED-based testing, but management patterns were different. Chest-pain patients were more likely to undergo electrocardiogram and x-ray testing, whereas dizzy patients more often received testing such as brain computed tomography scanning (10.8% v 3.6%, P = .01). ED patients with dizziness and chest pain were similar with regard to ED length of stay. Given their overall similarities to the chest-pain group, dizzy patients appear to represent a significant population of ED patients and may warrant more clinical study.

Adult↗
PubMed1994

Cell cycle kinetics in rat prostatic epithelia: nuclear migration during G2 phase.

Proliferative events in luminal epithelial cells of the rat ventral prostate were studied in 2 experiments. In experiment 1 a longitudinal survey of the rat prostate was conducted between 22 and 88 days of age. The pattern of temporal changes in the weight of the ventral prostate paralleled that of the testis, an observation consistent with the knowledge that the prostate is an androgen target organ. However, the total number of mitotic cells per prostate showed a biphasic pattern of distribution. The count was high (82 per prostate) in the prostate of 22-day-old rats and it decreased to a low value (25 per prostate) by age 30 days, a period corresponding to the onset of puberty in rats. The total mitotic count per prostate increased gradually and reached a peak (85 per prostate) around age 60 days when it started to decline gradually despite a continuous increase in prostatic weight. In experiment 2 cell cycle parameters of these cells were determined in young adult rats (age 70 days or 250 gm. body weight) by an in vivo 3H-thymidine pulse-chase approach. The apparent duration of various phases of the cell cycle was estimated as G1--11.5 hours, S--6.5 hours, G2--3.0 hours, M--2.0 hours and total cell cycle--23 hours. The fraction of cells in the S phase was 2.1%, which was extrapolated to give rise to a total growth fraction of 7.4%. In addition, it was noted that there was a migration of the nucleus from the base toward the apex of the epithelial cells during the G2 phase of the cell cycle in preparation for cell mitosis. Following mitosis nuclei of the 2 daughter cells returned to the usual basal position. These parameters will be used as basis of our future kinetic studies in the rat prostate.

Animals↗
PubMed1994

Effect of glutathione and its related enzymes on chemosensitivity of renal cell carcinoma and bladder carcinoma cell lines.

Glutathione and glutathione-related enzymes have been implicated in sensitivity of tumors to chemotherapeutic drugs. In the present study, glutathione and the activity of its related enzymes were quantitated in 4 renal cell carcinoma cell lines and 4 bladder carcinoma cell lines. The expression of glutathione-s-transferase pi and alpha in each cell line was analyzed by immunoblot analysis. The relationships between glutathione levels, glutathione peroxidase activity and glutathione-s-transferase activity and tumor sensitivity to cisplatinum, doxorubicin and vinblastine were determined by linear regression analysis. Glutathione levels were positively related to cisplatinum resistance in both renal cell carcinoma and bladder carcinoma cell lines and to doxorubicin resistance in bladder carcinoma cell lines. A positive correlation between glutathione peroxidase activity and doxorubicin resistance was identified in renal cell carcinoma cell lines, but no correlation was noted in bladder carcinoma cell lines. No significant correlation was apparent between glutathione-s-transferase activity and sensitivity to any of the drugs tested in this study. To further clarify the relationship between glutathione levels and the cytotoxicity of the drugs, we evaluated the effect of glutathione depletion by L-buthionine sulfoximine on the cytotoxicity of the drugs in bladder carcinoma cell lines. Glutathione depletion enhanced cisplatinum cytotoxicity 1.3- to 1.7-fold and doxorubicin cytotoxicity by 1.45- to 11.2-fold. Glutathione depletion did not change vinblastine cytotoxicity. The present study demonstrates that glutathione and its related enzymes affect sensitivity to cisplatinum or doxorubicin. The drug resistance mechanism elicited by glutathione and its related enzymes in these tumors needs further elucidation so that chemotherapeutic regimens may be modified.

Carcinoma, Renal Cell↗
PubMed1994

1H magnetic resonance spectroscopy characterization of neuronal dysfunction in drug-naive, chronic schizophrenia.

RATIONALE AND OBJECTIVES: We investigated the proton metabolism of right prefrontal white matter in drug-naive, chronic schizophrenic patients (n = 23), compared with healthy normal control subjects (n = 10), by using localized, water-suppressed in vivo 1H magnetic resonance (MR) spectroscopy. METHODS: All 1H MR spectroscopy examinations were performed on a 1.5-T MR imaging/MR spectroscopy system by using a point-resolved spectroscopy pulse sequence for localized volumes of 2 x 2 x 2 cm3. Proton metabolite ratios relative to creatine (Cr) were obtained using a Marquart algorithm. RESULTS: Drug-naive, chronic schizophrenic patients demonstrated a decrease in the N-acetylaspartate (NAA):Cr and choline (Cho):Cr ratios and an increase of the complex of gamma-aminobutyric acid (GABA) and glutamate (Glu)-containing ratio [(GABA + Glu):Cr] as compared with normal control subjects. CONCLUSION: Results suggest that the reduction of NAA and Cho may indicate neuronal dysfunction and that the elevation of GABA and Glu may play a role in chronic schizophrenia. 1H MR spectroscopy may be a useful modality in research and in the clinical evaluation of chronic schizophrenic patients.

Adolescent↗
PubMed1994

Use of desflurane during resection of phaeochromocytoma.

A patient underwent elective removal of a phaeochromocytoma producing extremely high plasma concentrations of catecholamines. The new volatile agent, desflurane, was incorporated, in varying concentrations, into the general anaesthetic regimen.

Adrenal Gland Neoplasms↗