Schrödinger fields on the plane with
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Journal Article↗
Biomedical subjects
C Lee
Publications and source records attributed to C Lee.
The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor.
The hepatitis C virus (HCV) nonstructural protein 3 (NS3) domain has been predicted from sequence comparisons to represent a trypsin-like serine protease. By expressing wild-type and mutant HCV-1 cDNAs in transfected mammalian cells, we have identified putative nonstructural proteins 3 (72 kDa), 4 (10 kDa and 27 kDa) and 5 (58 kDa) and have shown that their processing from the viral polyprotein precursor is dependent on Ser1165 located in the proposed protease catalytic site. Data obtained from in vitro RNA translations indicate that unlike the processing of the NS2/NS3 junction, NS3/NS4 processing is dependent on Ser1165. In contrast to the situation for the related flaviviral NS3 proteases, the HCV NS3-mediated cleavage of the NS3/NS4 junction does not require the upstream NS2 domain and may not occur at dibasic sites.
Animals↗
Car-Parrinello molecular dynamics with Vanderbilt ultrasoft pseudopotentials.
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Journal Article↗
Ab initio studies on the structural and dynamical properties of ice.
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Journal Article↗
3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency.
3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL) catalyzes the final step of ketogenesis, an important pathway of mammalian energy metabolism. HL deficiency is an autosomal recessive inborn error in man leading to episodes of hypoglycemia and coma. Using the N-terminal peptide sequence of purified chicken liver HL, we designed degenerate sequence primers and amplified an 89-base pair (bp) chicken liver HL cDNA fragment. Longer cDNA clones for chicken (1384 bp) and human (1575 bp) HL were obtained by library screening. The peptide sequence predicted from the chicken clone contains two peptides from purified chicken HL. Mature human and chicken HL are 298-residue peptides. The sequence of the human clone predicts a 27-residue mitochondrial leader and a 31.6-kDa mature HL peptide. Human fibroblast and liver RNA contain a single 1.7-kilobase HL message. Two Acadian French-Canadian siblings with HL deficiency were homozygous for a 2-base pair deletion within the Ser-69 codon (S69fs(-2)), predicted to result in a truncated nonfunctional HL peptide lacking a complete active site. S69fs(-2) was not present in 12 other HL-deficient patients of 10 other ethnic origins, showing that HL deficiency is genetically heterogeneous.
Amino Acid Sequence↗
Growth of an androgen-sensitive human prostate cancer cell line, LNCaP, in nude mice.
This study was undertaken to establish an androgen-sensitive model of human prostatic carcinoma in nude mice. The androgen-sensitive prostatic carcinoma cell line, LNCaP, was suspended in reconstituted basement membrane (Matrigel) and injected subcutaneously into nude mice. The LNCaP cell line was chosen for the study, because the cell line is androgen-sensitive and secretes prostate specific antigen (PSA) into culture media. Following injection of 1 x 10(6) LNCaP cells with 0.25 ml of Matrigel, 88% of mice exhibited palpable tumor burdens after 12 weeks of observation. In addition, significant levels of PSA were observed in the serum of LNCaP-bearing mice. Bilateral orchiectomy of mice resulted in tumor regression and stabilization of serum PSA levels, compared to testis-intact controls. A significant correlation of PSA to tumor volume and weight was observed. The castrate level of testosterone was confirmed by radioimmunoassay and was similar to testosterone levels in female nude mice. Matrigel allows for a conducive environment to propagate LNCaP cells in nude mice. Furthermore, the growth can be manipulated by castration, leading to involution of tumor and stabilization of serum PSA level. This in vivo model of hormone-sensitive human prostate cancer cell line will serve as a model for the study of prostate tumor biology and treatment.
Animals↗
Synthesis and use of fluorescent molecular probes for measuring cell-surface enzymatic oxidation of amino acids and amines in seawater.
A method for investigating cell-surface enzymatic oxidative deamination of amino acids and amines in seawater was developed. This technique used synthetic fluorescent Lucifer Yellow derivatives of the amino acid lysine and the amine cadaverine as molecular probes to investigate oxidation pathways and rates. The probes were chemically stable under the conditions used and did not adsorb to container surfaces. The oxidative deamination of the fluorescent probes added to phytoplankton cultures and the subsequent production of their fluorescent oxidation products could be selectively detected by HPLC at 250 pM levels. This approach allows selective investigation of cell-surface enzymatic oxidation since neither transport of the probes across the cell membrane nor chemical transformation of the probes occurs. Bacteria were also capable of oxidizing the fluorescent amino acid probe.
Adsorption↗
Neuropsychological sequelae of Wernicke's encephalopathy in a 20-year-old woman: selective impairment of a frontal memory system.
This article reports the neuropsychological sequelae of Wernicke's Encephalopathy in a 20-year-old woman. After amelioration of acute symptoms, the patient showed a range of cognitive impairments the most marked of which was a severe impairment on free recall tasks involving both verbal and nonverbal material. In contrast, recognition memory appeared remarkably well preserved. Some evidence of frontal lobe and general intellectual impairment was also noted. The case is discussed in terms of the pathophysiology of Wernicke-Korsakoff Syndrome, criteria for its diagnosis, and the multicomponent nature of memory deficits.
Adult↗
Regional localization of 32 NotI-HindIII fragments from a human chromosome 13 library by a somatic cell hybrid panel and in situ hybridization.
Relatively few DNA probes have been regionally assigned to chromosome 13 bands, and these tend to be clustered in the proximal end of the chromosome in the regions where intensive mapping efforts have been focused because of the retinoblastoma and Wilson disease genes. We have developed a chromosome 13-specific half-linking library of NotI-HindIII fragments and regionally mapped 32 of these on chromosome 13, using a somatic cell hybrid panel that subdivides chromosome 13 into 11 regions and nonisotopic in situ hybridization with silver amplification of a digoxigenin-labeled probe.
Animals↗
Motility and construction of the endoplasmic reticulum in living cells.
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Animals↗
Atomic force microscopy of mammalian sperm chromatin.
We have used the atomic force microscope (AFM) to image the surfaces of intact bull, mouse and rat sperm chromatin and partially decondensed mouse sperm chromatin attached to coverglass. High resolution AFM imaging was performed in air and saline using uncoated, unfixed and unstained chromatin. Images of the surfaces of intact chromatin from all three species and of an AFM-dissected bull sperm nucleus have revealed that the DNA is organized into large nodular subunits, which vary in diameter between 50 and 100 nm. Other images of partially decondensed mouse sperm chromatin show that the nodules are arranged along thick fibers that loop out away from the nucleus upon decondensation. These fibers appear to stretch or unravel, generating narrow smooth fibers with thicknesses equivalent to a single DNA-protamine complex. High resolution AFM images of the nodular subunits suggest that they are discrete, ellipsoid-shaped DNA packaging units possibly only one level of packaging above the protamine-DNA complex.
Animals↗
Isolation and identification of a novel tandemly repeated DNA sequence in the centromeric region of human chromosome 8.
EcoRI subclones, designated as 50E1 and 50E4, were independently obtained from a cosmid clone previously mapped to the centromeric region of human chromosome 8. Southern blot hybridization analyses suggested that both subclones contain repetitive DNA sequences different from the chromosome 8 specific alphoid DNA. DNA sequence analysis of the 704 bp insert of 50E1 and the 1,962 bp insert of 50E4 revealed that both inserts contained tandemly repeated units of approximately 220 bp. Fluorescence in situ hybridization studies confirmed these two subclones to be specifically located on the centromeric region of chromosome 8. A 220 bp consensus sequence, derived from nine monomeric repeats, showed no significant homology to alphoid consensus sequences or to other currently known human centromeric DNA sequence. Furthermore, no significant homology was found with any other DNA sequence deposited in the EMBL or GenBank databases, indicating that this chromosome 8 specific repetitive DNA sequence is novel. From slot blot experiments it was estimated that 0.013% of the human genome comprises 1,750 of these monomeric repeats, residing on the centromeric region of chromosome 8 in tandem array(s).
Base Sequence↗
In vivo and in vitro approaches to study metastasis in human prostatic cancer.
Prostate cancer is the most common malignancy in American males and is second only to lung cancer as a cause of death in the United States. Clinically, radical prostatectomy offers a patient with locally contained disease an excellent chance for cure. For patients with metastatic disease, the current therapies are merely palliative. Understanding the biology of prostate cancer metastasis should facilitate the development of novel and effective therapeutic modalities. Crucial to this objective is the availability of human tumor systems in which the biology of metastasis can be studied. The present chapter will briefly assess various in vivo and in vitro approaches to study metastasis in human prostate cancer. Utilization of athymic nude mice has played an important role in maintaining human prostatic cancer cells as xenografts and has provided an opportunity to establish site-specific subpopulations of the parental cell lines for further characterization and investigation. At present, a few established cell lines have been useful for this purpose. Fresh tumor specimens, unfortunately, have shown limited ability to grow in nude mice. The recent development of novel approaches to permit the maintenance of freshly harvested prostate cancers has been encouraging. The use of reconstituted basement membrane (Matrigel) for co-injection with cancer cells into the subcutaneous tissues has supported growth of biologically indolent tumors. Another approach is to administer tumor cells orthotopically into the prostate of recipient nude mice. Bone marrow metastases in nude mice have been rare in the past. Recently, three approaches have been shown to be successful in accomplishing bony metastasis with PC-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Factors related to the adoption of exercise among older women.
The role of exercise in promoting health is well documented; however, older women have the lowest rates of aerobic exercise of any community group. This paper examines psychological variables relevant to women's initial adoption of exercise. While the evidence is limited, it appears that middle-aged and older women have positive attitudes to exercise but seem unable or unwilling to take action. The influence of practical barriers and of broader social attitudes is considered. It is concluded that social psychological variables have had limited success in explaining sex differences in physical activity. An understanding of practical and societal constraints on behavior choice in a broader social context may provide direction for the development of strategies to improve the exercise levels of this community group.
Adult↗
Refractoriness of neuromuscular transmission: determination by computer subtraction of neurally evoked compound electromyograms.
Shortly after elicitation of a muscle response by supramaximal stimulation of its motor nerve, there exists a period of refractoriness of neuromuscular transmission when a second stimulation elicits only a submaximal response or no response at all. Many anaesthetics and neuromuscular blocking and facilitatory drugs change the refractoriness of neuromuscular transmission. Measurement of this refractoriness may improve our understanding of the neuromuscular actions of these drugs and be useful in differential diagnosis. However, the neuromuscular refractory periods (RP) are difficult to measure, and the unavailability of normal values renders accurate determination of drug effects impossible. Based on an existing technique of digitization and time expansion of the neurally evoked compound electromyogram (ncEMG), we developed a computer programme of waveform subtraction, and determined in nine normal awake volunteers the various interstimulus intervals when neuromuscular transmission was refractory (RP0), 3/4 refractory (RP.25), half refractory (RP.5), 1/4 refractory (RP.75) or non-refractory (RP1). We confirmed our hypotheses that computer-based waveform subtraction of the digitized ncEMG is a feasible and necessary technique for the accurate determination of the RPs of neuromuscular transmission, and report that the normal values in humans are: RP0 = 1.0 +/- 0.1, RP.25 = 1.3 +/- 0.3, RP.5 = 1.9 +/- 0.3, RP.75 = 2.9 +/- 0.5, and RP1 = 6.6 +/- 1.9 ms (mean +/- SD), respectively, in the ulnar nerve-first dorsal interosseous muscle model.
Adult↗
A clinical assessment of desflurane anaesthesia and comparison with isoflurane.
In 48 randomly assigned ASA I adult patients undergoing elective orthopaedic procedures, we compared the pharmacodynamics of desflurane (DF) and isoflurane (IF), and their pharmacokinetics during rapid induction of deep anaesthesia (via face mask, to 1.5-2 MAC, after thiopentone), maintenance of anaesthesia at 1.25 MAC, and emergence therefrom. During induction, laryngeal reactions ranging from mild crowing to laryngospasm occurred more frequently with DF than with IF (15/24 DF, 5/24 IF; P < 0.05) and was more severe (9/24 DF, 1/24 IF, excluding the mildest form, P < 0.05). As a result, induction of anaesthesia was not accomplished faster with DF, in spite of a faster equilibration between exhaled and inhaled concentrations. Emergence from DF was more rapid and less complicated by delirium. Pharmacokinetically, the exhaled concentration of DF reached 90% of the inhaled concentration within five minutes of induction, whereas that of IF lagged behind and remained 25% below the inhaled concentration (1 vs 1.34 +/- 0.05) even one hour after induction. Premature ventricular contractions did not occur in any patient even during periods of difficulty with the airway and oxygen desaturation. It is concluded that DF is a safe anaesthetic, pharmacokinetically superior to IF but clinically inferior for induction of anaesthesia via a face mask. Because of the fast equilibration, the exhaled concentration of DF can be controlled more precisely by the dial setting of the vaporiser.
Adolescent↗
Immunohistochemical localization of epidermal growth factor and transforming growth factor alpha in the male rat accessory sex organs.
We examined the presence of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) in the prostate (ventral, lateral, dorsal lobes), coagulating gland and seminal vesicle of Fisher 344 adult male rats by immunohistochemical and radioimmunoassay methods. Immunohistochemically demonstrable EGF was localized in the luminal secretion only of the dorsal lobe of the prostate. Reactive TGF alpha was localized in the lateral lobe (100% of epithelial cells), dorsal lobe (about 40% of the epithelial cells) and seminal vesicle (100% of epithelial cells), but not in the coagulating gland or ventral lobe of the prostate. Radioimmunoassay also demonstrated a measurable amount of TGF alpha in the lateral lobe (194 pg./gm. wet weight) and seminal vesicle (74 pg./gm.). Assayable EGF was demonstrated at much higher levels in all prostate lobes (ranging from 1.2 micrograms./gm. wet weight in the ventral lobe to 26.4 micrograms./gm. in the dorsal lobe) and wet weight in the ventral lobe to 26.4 micrograms./gm. in the dorsal lobe) and the seminal vesicle (0.9 micrograms./gm.). This is the first report describing the presence of immunoreactive TGF alpha and EGF in the male accessory sex organs.
Animals↗
Effect of retinoic acid on the proliferation and secretory activity of androgen-responsive prostatic carcinoma cells.
We studied the effect of retinoic acid on the growth and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. Our data showed that retinoic acid at 0.01 microM. stimulated the proliferation of LNCaP cells but inhibited their growth at 0.1 microM. under androgen-free conditions. In the presence of 0.1 nM. dihydrotestosterone (DHT), LNCaP cell proliferation was inhibited by 10 microM. retinoic acid but not by lower concentrations of retinoic acid. Retinoic acid reduced LNCaP cell growth at concentrations of 0.1 microM. in the presence of 10 nM. DHT. Retinoic acid (10 microM.) also reduced the growth response of LNCaP cells to epidermal growth factor and transforming growth factor alpha and potentiated the inhibitory effect of transforming growth factor beta. In additional studies, retinoic acid induced a dose-dependent increase in prostate specific antigen (PSA) secretion at concentrations of 0.1 to 1 microM. Dihydrotestosterone (10 nM.) also enhanced the secretion of PSA by LNCaP cells, and this effect was potentiated in a dose-dependent fashion by the addition of retinoic acid at 0.1-10 microM. Competitive binding studies showed that retinoic acid did not bind to androgen receptors. Overall, retinoic acid had a biphasic effect on LNCaP proliferation and promoted the secretion of PSA. The biphasic effect of retinoic acid on LNCaP growth should be considered in designing in vivo studies to determine the impact of retinoic acid on solid prostatic tumor growth. In addition, the ability of retinoic acid to increase PSA secretion may complicate the interpretation of serum PSA levels used for diagnostic and prognostic purposes.
Androgens↗