Search PubMed⌕ Search

Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 451 records · Page 25Linked to original sources
PubMed1997

Fibroblasts that overexpress 15-lipoxygenase generate bioactive and minimally modified LDL.

Several lines of evidence suggest that the cellular enzyme 15 lipoxygenase (15-LO) may be important in promoting the oxidation of lipoproteins in vivo. In previous studies we have shown that fibroblasts transfected with 15-LO "seed" LDL with lipoperoxides such that subsequent oxidation readily generates an LDL that is taken up by macrophages through scavenger receptors. We now demonstrate that LDL incubated with 15-LO cells is "minimally modified" and has bioactive properties. Characterization of LDL incubated with 15-LO cells reveals that lipid peroxidation is modest, with low levels of TBARS generated (12.6 +/- 4.7 nmole MDA per mg protein) and small amounts of 18:2 lost as a result of oxidation (7%, compared with extensive loss [82%] with copper oxidation). The 15-LO-conditioned LDL showed mildly increased electrophoretic mobility on agarose gels, and on polyacrylamide gels it showed only mild protein degradation compared with copper-oxidized LDL. Additionally 15-LO-conditioned LDL competed very well for the LDL receptor of fibroblasts but did not compete for macrophage uptake of 125I-acetylated LDL. Importantly, compared with LDL incubated on beta-galactosidase (lac Z)-transfected control cells, LDL incubated on 15-LO cells stimulated monocyte chemotaxis (15-LO-LDL, 6.9 +/- 1.2 monocytes per field versus lac Z-LDL, 0 +/- 0.9 monocytes per field) and when added to endothelial cells enhanced adhesion (15-LO-LDL, 31.1 +/- 5.0 monocytes per field versus lac Z-LDL, 0 +/- 2.0 monocytes per field). Preincubation of 15-LO cells with 15-LO inhibitors significantly inhibited the generation of bioactive LDL. Lipid extracts of LDL conditioned on 15-LO cells showed chemotactic activity not related to lysophosphatidylcholine levels. Preincubation of target endothelial cells with several different platelet-activating factor receptor antagonists prevented stimulation of monocyte adhesion by 15-LO-conditioned LDL. When probucol- or vitamin E-enriched LDL was incubated with 15-LO cells it was less oxidized and less bioactive, which suggests that these cells seed LDL with LOOH, which then requires further propagation of lipid peroxidation to yield bioactivity. These studies demonstrate that fibroblasts expressing 15-LO reliably produce a bioactive "minimally modified" LDL, which may explain in part how cellular 15-LO activity may generate atherogenic LDL in vivo.

Animals↗
PubMed1997

Effect of haloperidol on nicotine-induced enhancement of vigilance in human subjects.

We posed the question whether the cognitive enhancement caused by nicotine in human subjects is mediated by dopamine (DA) release. This issue was addressed by testing performance in the Wesnes and Warburton vigilance task after s.c. nicotine with or without concomitant oral haloperidol. The subjects were moderate (10-14 cigarettes/day) smokers after overnight deprivation of smoking. After an initial practice session, each subject participated in four further sessions spread over 2 weeks, after: placebo/placebo, placebo/haloperidol (5 mg), placebo/nicotine (0.8 mg) or nicotine/haloperidol, double-blind with a balanced ordering of drug combinations. On each occasion, performance was measured on the vigilance task, a finger tapping test, and digit span forward and backward. Nicotine improved detection sensitivity on the vigilance task, and this effect was unchanged by haloperidol; the latter compound reduced forward digit span. Thus, the improved vigilance caused by nicotine does not appear to be mediated by DA systems.

Adolescent↗
PubMed1997

Transforming growth factor-beta1 inhibits membrane association of protein kinase C alpha in a human prostate cancer cell line, PC3.

The postreceptor signaling pathway(s) that mediates the effects of transforming growth factor-beta1 (TGF-beta1) is incompletely understood. The present study investigated the involvement of protein kinase C (PKC) in the growth-inhibitory action of TGF-beta1 in PC3, a human prostate cancer cell line. PKC alpha, the only conventional PKC isoform detected in PC3 cells, appeared to be constitutively active based on its presence in both Triton-soluble membrane fraction and cytosol. However, levels of membrane-associated PKC alpha were decreased by a growth-inhibitory dose of TGF-beta1. The response to TGF-beta1 was rapid (within 5 min), time dependent, isoform specific, and occurred without apparent changes in levels of total PKC alpha protein. TGF-beta1 also decreased the levels of membrane-associated PKC activity coincident with its inhibitory effect on PKC alpha's membrane association. Inhibition of PKC activity appeared to be associated with growth inhibition in PC3 cells, because chelerythrine (a specific PKC inhibitor) likewise decreased cell proliferation. Taken together, our data suggest that inhibition of PKC activity, at least in part due to inactivation of PKC alpha, is an early event associated with TGF-beta1 postreceptor signaling that might mediate suppression of cell proliferation.

Alkaloids↗
PubMed1997

Autocrine effect of androgen on proliferation of an androgen responsive prostatic carcinoma cell line, LNCAP: role of interleukin-6.

LNCaP is an androgen-responsive prostatic carcinoma cell line that exhibits a bell-shaped growth response curve to increasing doses of dihydrotestosterone (DHT) in culture. Although the precise mechanism responsible for this unique growth response to androgen stimulation remains unclear, many studies have suggested that androgen modulates the level of various growth factors. In an early study, we demonstrated that LNCaP proliferation was stimulated by interleukin (IL)-6 in a paracrine manner, because these cells did not express a significant amount of IL-6. In the present study, the role of IL-6 in mediating androgen regulated proliferation in LNCaP cells was investigated. DHT, at increasing doses up to 10(-8) M, resulted in a release of IL-6 from LNCaP cells. This dose-dependent effect of DHT on LNCaP proliferation could be partially inhibited by the addition of antibody against IL-6 into the culture medium. These results indicate that the DHT-induced expression of IL-6 stimulates proliferation of LNCaP cells in culture in an autocrine manner.

Androgens↗
PubMed1997

Presynaptic and postsynaptic striatal dopaminergic function in patients with manganese intoxication: a positron emission tomography study.

We performed PET on four patients with chronic industrial Mn intoxication; presynaptic and postsynaptic dopaminergic function were measured with [18F]6-fluoro-L-dopa (6FD) and [11C]raclopride (RAC). All patients had a rigid-akinetic syndrome; they had no sustained benefit from L-dopa. Influx constants (Ki) of 6FD were normal in the caudate and putamen. RAC binding was mildly reduced in the caudate and normal in the putamen. We conclude that nigrostriatal dopaminergic dysfunction is not responsible for the parkinsonism caused by chronic Mn intoxication. The pathology is likely to be downstream of the dopaminergic projection.

Adult↗
PubMed1997

Influence of sire misidentification on sire x year interaction variance and direct-maternal genetic covariance for weaning weight in beef cattle.

Biased estimates of the genetic correlation between direct and maternal effects may occur when sire x year interaction (SY) effects are ignored in analytical models used to estimate (co)variance components for weaning weight in beef cattle. Using simulation, sire misidentification was explored as a source contributing to estimates of SY variance. Identifications were falsified for 20% of sires of nonparents only or for 20% of sires of all animals. Sire misidentification influenced estimates of genetic and environmental parameters. In populations in which misidentification occurred only in nonparents, heritability estimates for direct growth were reduced, and heritability estimates of maternal effects were inflated. Also, spurious SY variance and direct-maternal covariance were produced. Direct-maternal covariance was biased in a positive direction, and SY variance was on the order of 1 to 3% of the phenotypic variance.

Aging↗
PubMed1997

Influence of partitioning data by sex on genetic variance and covariance components for weaning weight in beef cattle.

Heterogeneity of (co)variance components (VC) by sex is currently accounted for in national genetic evaluations for Simmental cattle. Parameters used in the national evaluation program are estimated from data split into male, female, and steer populations. Analyzing only male data does not account for selection of females, and vice versa. To determine the impact of selection, a Monte Carlo simulation was used, and estimates of VC for weaning weight were obtained when data were partitioned by sex. Weaning weight data were simulated using homogeneous VC for males and females for random and selected populations. Restricted maximum likelihood estimates were obtained for direct and maternal genetic and permanent and temporary environmental variances and genetic covariance between direct and maternal effects by analyzing complete or split data. Estimates differed (P < .01) from input values in data from selected populations split by sex, yielding a spurious heterogeneity of VC for sex. The heterogeneity was reduced in models using genetic groups but not completely removed. Splitting data by sex also influenced VC estimates in data simulated with heterogeneous VC for males and females.

Aging↗
PubMed1997

Relationship between sire x year interactions and direct-maternal genetic correlation for weaning weight of Simmental cattle.

The interrelation of sire x year interactions (SY) and direct-maternal genetic correlation (rdm) for weaning weight was examined for bias in estimating rdm. Weaning weight records were simulated using models containing SY (D1), rdm (D2), or both (D3). When D1 data were analyzed ignoring SY, a nonzero rdm was observed, and direct and maternal genetic variance estimates were inflated. Analysis of D2 data ignoring rdm did not reveal a spurious SY, and direct and maternal genetic variance estimates were deflated. On application to weaning weights of Simmental cattle, the model ignoring SY resulted in a direct-maternal genetic correlation estimate of -.29. The model using both SY and rdm fit the data better (P < .01). The SY variance represented only 3% of phenotypic variance but explained 62% of the covariance between direct and maternal genetic effects estimated ignoring SY. However, a negative estimate of the genetic correlation (-.14) was still obtained.

Animals↗
PubMed1997

Estimation of genetic variance and covariance components for weaning weight in Simmental cattle.

The objectives of this study were to estimate genetic parameters for weaning weight of Simmental cattle from data without selective reporting and to examine heterogeneity of parameters with a multiple trait approach. Heterogeneity of (co)variance components (VC) by sex is accounted for in national genetic evaluations for Simmental cattle. Completely reported data were split into bull, heifer, and steer populations to obtain VC estimates. Estimates of direct-maternal genetic correlation were negative, which suggests that selective reporting was not a cause of a negative correlation in Simmental data. However, analyzing only data for males does not account for selection on females and vice versa. Heterogeneous VC for sex were evaluated by analyzing Simmental data using a multiple trait model where male and female data were treated as two traits. Estimates of heritability of direct (maternal) effects were .19 (.07) and .25 (.12) and estimates of the direct-maternal genetic correlation were -.05 and -.20 for males and females, respectively. The multiple trait model fit the data better (P < .01) than the model under the assumption of homogeneous VC.

Animals↗
PubMed1997

Hb Watts [alpha 74(EF3) or alpha 75(EF4)Asp-->0]: a shortened alpha chain variant due to the deletion of three nucleotides in exon 2 of the alpha 2-globin gene.

We have identified a new, slightly unstable alpha chain hemoglobin variant, present in a Mexican-American family. Amino acid sequencing and mass spectral analysis of the aberrant peptide (alpha T-9) of the variant revealed that the aspartic acid is deleted either at position 74 or 75 of one of the alpha-globin chains. Sequencing of the amplified alpha 2- or alpha 1-globin genes revealed a trinucleotide deletion (GAC) at codon 74 or 74 of the alpha 2 gene. Although the aspartic acid residues of 74 and 75 of the alpha chain are neither a heme nor an inter chain contact, the slight instability of Hb Watts may be due to disturbance of the central cavity of hemoglobin by the deletion of an aspartic acid residue in the EF helix. Hb Watts is the first example of a trinucleotide deletion in the alpha 2-globin gene.

Adult↗
PubMed1997

Epidemiology and clinical characteristics of HIV-infected patients in Kuala Lumpur.

Between 1987 to 1995, a total of 334 patients infected with HIV were treated at the Hospital Kuala Lumpur. There were 159 Malays, 108 Chinese, 64 Indians, and 3 from other ethnic groups. Three hundred and twenty-one (96.1%) of these individuals were males and 262 (65.9%) were between the ages of 26-45 years. Intravenous drug users made up 77% (256) of the attributable risk behaviour from the group although many of them also had added risk behaviours like heterosexual activity with multiple partners (50 patients), tattoos (7 patients), homosexual practice (4 patients) and previous transfusions (3 patients). The others acquired their infection through heterosexual promiscuity (59 patients), homo/bisexual activity (7 patients), previous transfusion (5 patients) and tattoos (1 patient). Sixty-six patients (all males) had since progressed to full blown AIDS and 10 have died. The two commonest AIDS-defining events were tuberculosis infection and Pneumocystic carinii pneumonia occurring in 37 (56%) and 15 (22.7%) of patients respectively. Forty-one patients with AIDS presented for the first time with their AIDS-defining infections. The mean CD4 count of the patients when they progressed to AIDS was 130/mm3. The mean time for progression from "known" seropositivity to AIDS was 2.42 years. These results suggest that Malaysians infected with HIV are not coming forward for treatment until they are in the advanced stage of the disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

Two-dimensional gel electrophoresis detects prostate-specific antigen-alpha1-antichymotrypsin complex in serum but not in prostatic fluid.

We investigated the interaction between prostate-specific antigen (PSA) and 1-antichymotrypsin (ACT) in prostatic secretions, identifying PSA and ACT in human serum, prostatic fluid, and seminal plasma by two-dimensional gel electrophoresis (2-D PAGE). Both PSA and ACT were detected in all three body fluids, but PSA-ACT complex was detected only in serum. Moreover, the 2-D PAGE Western blot staining profile for ACT from serum differed from that for prostatic fluid or seminal plasma. Incubation of prostatic fluid with purified ACT led to formation of PSA-ACT complex. Incubation of prostatic fluid with purified PSA, however, failed to form the complex, suggesting that the ACT in prostatic fluid was inactive or inhibited. Given that physiological concentrations of zinc inhibited the formation of PSA-ACT complex, we consider zinc a possible physiological inhibitor of the formation of the PSA-ACT complex. These results indicate that the failure to detect the PSA-ACT complex in prostatic fluid could be related to the inactivation of ACT, the presence of inhibitors (e.g., zinc), or simply the PSA:ACT ratio in the fluid.

Adult↗
PubMed1997

Counseling clinic for pediatric weight reduction: program formulation and follow-up.

The feasibility and efficacy of an outpatient-based multicomponent weight reduction program was tested with 68 consecutively enrolled obese children and adolescents. The patients were invited to participate in an individualized six-session program that included parent involvement, diet education, exercise management and behavior modification by a culturally sensitive method. Fifty-six patients were followed up 1 year after treatment. Comparison at pretreatment, end-of-treatment and 1-year-after-treatment with respect to changes in degree of obesity, measured by weight-for-length index (WLI), showed statistically significant differences. Ninety-seven percent of participants were below their pretreatment WLI at the end-of-treatment examination, and 80% at 1-year-after-treatment follow-up. At 1-year-after-treatment, 59% showed a reduction in WLI of 0.1 or more, as compared with 38% of participants at end-of-treatment. Two parameters previously considered predictors of successful weight control, notably age of participants and percentage of weight lost during treatment, were significantly associated with a reduction in the degree of obesity after one year. Although the long-term efficacy cannot be determined, our results indicated that this comprehensive weight reduction program may have an encouraging effect on the weight status of obese Chinese children and adolescents.

Adolescent↗
PubMed1997

Genomic regions of coxsackievirus B3 associated with cardiovirulence.

The molecular basis for cardiovirulence in the coxsackievirus B3 (CVB3) genome was examined in a murine model of acute myocarditis. Infectious cDNAs representing a highly cardiovirulent coxsackievirus B3 (CVB3m) and a noncardiovirulent (CVB30) virus were used to construct infectious chimeric cDNAs. Assays of the resulting recombinant viruses for cardiovirulence in adolescent male CD-1 mice showed that the 5' nontranslated region (5' NTR) of the CVB3m genome plays the major role in determining cardiovirulence and that the genomic region encoding the capsid proteins has a minor additive effect in increasing cardiovirulence. Nucleotide sequences in the 5' NTR of CVB3m and CVB30 differ at 23 positions; 14 are located in four stemloop motifs of the secondary structure and may influence the cardiovirulent phenotype by regulating RNA or protein synthesis. A comparison of predicted amino acid sequences of capsid proteins in CVB3m and CVB30 identified two amino acids as potential candidate contributors to cardiovirulence, i.e., amino acids at positions A207 (Asn-Asp) in the puff structure of the E-F loop of VP2 and A566 (Gln-Glu) in the C terminal of VP3 at the external surface. The data from this study and published literature support the conclusion that cardiovirulence of a CVB3 can depend on several regions of the genome.

Animals↗
PubMed1997

The results of open acromioplasty in impingement syndrome--a retrospective study.

Many published reports have reported generally good results of open acromioplasty in shoulder impingement syndrome. This paper studied retrospectively the results of open acromioplasty done in the Singapore General Hospital. A total of 23 open acromioplasties performed on 22 patients with shoulder impingement syndrome were studied. The post-operative results of the acromioplasties were evaluated using the University of California, Los Angeles (UCLA) shoulder scoring system. With the UCLA shoulder scoring system, results were excellent or good in 14 (60.8%), fair in 7 (30.5%) and poor in 2 (8.7%). At the same time the male sex was identified to have statistically significant better results as compared to the females. There was a trend towards poorer results in those at or above 50 years of age, duration of symptoms of less than 2 years and those with acromiohumeral distance of less than or equal to 1.0 cm. The presence of rotator cuff tears and the duration of follow-up were found not to have any bearing on the post-operative outcome. This procedure seems to be reasonably effective and safe. Careful patient selection and early post-operative rehabilitation with physiotherapy is of utmost importance.

Acromioclavicular Joint↗
PubMed1997

Patterns and correlates of hormone replacement therapy use among middle-aged Australian women.

In this study, we examine the patterns of use of hormone replacement therapy (HRT) among women age 51 to 60 years and describe the characteristics of women who currently use HRT, previously used HRT, and have never used HRT. A brief postal survey of 800 women in this age range was used to determine HRT status. Telephone interviews were then conducted with 258 women (111 currently using HRT, 47 who previously used HRT, and 100 who had never used HRT) to determine characteristics of women who currently or previously used HRT or never used HRT, type of HRT used, duration of use, and reasons for use and nonuse. Nearly 40% of women were currently using HRT, 14% had previously used HRT, and 47% had never used HRT. Women currently using HRT were more likely than those not using HRT to have had a hysterectomy, attribute a greater number of symptoms to the climacteric, be in paid employment, and report a greater number of visits to the doctor over the past 12 months. HRT use among Australian women in their 50s is high and rising. Hysterectomy status, the attribution of symptoms to menopause, paid employment, and health care use were the most important correlates of HRT use. Few women specified long-term prevention of osteoporosis or heart disease as a reason for taking HRT.

Analysis of Variance↗
PubMed1997

Packing as a structural basis of protein stability: understanding mutant properties from wildtype structure.

Modeling of protein core mutations using sidechain packing can forecast their effects on stability. We have assessed the structural basis of this approach, by evaluating the accuracy of our 1991 model of a three-site mutant of lambda repressor (V36L/M40L/V47I), against the recently reported crystal structure. The three mutated residues matched the crystal structure to within 0.89A (1.11A for sidechain atoms), giving fairly accurate sidechain placement and packing (81-99th percentile rank in coordinate accuracy). However, the model used different sidechain torsional angles than seen in the crystal structure at residues 36 and 40, apparently to compensate for the backbone shifts present in the actual mutant structure, but not accounted for in our modeling method. To understand the structural basis of stability across a set of lambda repressor core mutants, we have analyzed the mutant models, revealing several simple packing effects: V36I, predicted to be stabilized by filling a hydrophobic cavity; M40V, destabilized by a steric clash with the unusual structural demands of a helix-turn transition. These effects illustrate how mutant stability can often be understood directly from scrutiny of wildtype structure. Simply adding the calculated energies of neighboring point mutations predicts the stability effect of the combined mutant relatively well, with little apparent cooperativity, yielding simple rules for each site's amino acid preferences. Our treatment of core packing indicates that it can permit a large fraction of sequences to fit the native fold, as observed experimentally, far more than indicated by rotamer hard-sphere models.

Amino Acid Sequence↗