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Biomedical subjects

L J Lee

Publications and source records attributed to L J Lee.

At least 19 recordsLinked to original sources
PubMed2004

Dynamics of single polymers in a stagnation flow induced by electrokinetics.

An electrokinetics-induced stagnation flow was created inside a microscale cross-channel. Compared to hydrodynamic-induced microfluidics, this flow system can be readily assembled and the operation is very simple due to a low pressure drop. Through image analysis, a fairly homogeneous, two-dimensional elongational flow was observed. The initial conformation of DNA molecules and residence time inside the flow field play important roles in determining the extent of DNA stretching. A coarse-grain molecular simulation agrees reasonably well with experimental observations.

Computer Simulation↗
PubMed2001

Mechanism of colchicine-induced steroidogenesis in rat adrenocortical cells.

Conflicting data for the effects of colchicine on cholesterol transport and steroidogenesis raise the question of the role of microtubules in cholesterol transport from the lipid droplet to mitochondria in steroidogenic cells. In this study, using corticosterone radioimmunoassay and immunofluorescence microscopy, we re-evaluated the effects of colchicine on hormone production and morphological changes of lipid droplets' and studied the signaling pathway involved in colchicine-induced steroidogenesis. Colchicine stimulated steroid production in a dose- and time-dependent manner. The structural integrity of both the microtubules and the lipid droplet capsule was destroyed by colchicine treatment. Disruption of the lipid droplet capsule occurred later than microtubule depolymerization. After cessation of colchicine treatment and a 3 h recovery in fresh medium, capsular protein relocated to the droplet surface before the cytoplasmic microtubule network was re-established. beta-lumicolchicine, an inactive analogue of colchicine, disrupted the capsule and increased hormone production without affecting microtubular structure. Thus, microtubule depolymerization is not required for the increase in steroid production and capsular disruption. To explore the signaling pathway involved in colchicine-induced steroidogenesis, we measured intracellular cAMP levels. Unlike ACTH, colchicine did not increase cAMP levels, suggesting that the cAMP-PKA system is not involved. Colchicine and ACTH had additive effects on corticosterone production, whereas colchicine and PMA did not, implying that part of the PKC signaling mechanism may be involved in colchicine-induced steroidogenesis. Cycloheximide, a protein synthesis inhibitor, completely inhibited colchicine-induced steroidogenesis and capsular disruption. These results demonstrate that the steroid production and lipid droplet capsule detachment induced by colchicine are both protein neosynthesis-dependent and microtubule-independent.

Adrenal Cortex↗
PubMed2001

Drug offenders in Taiwan and the United States: a cross-cultural analysis.

Using data collected from nationwide surveys of drug-using offenders in the United States and Taiwan, this article compares offender differences with respect to socio-demographic characteristics, childhood experiences, drug use and treatment patterns, and criminal histories. The results suggest that the experiences of U.S. drug-using offenders are more complex, with multiple routes and consequences of drug use, while the social constructionist view is more appropriate to explain the experience of Taiwanese drug-using offenders. Overall, U.S. drug-using offenders reported earlier drug and criminal involvement, experienced more prior arrests, and committed more non-drug-related crimes. Family problems were more prevalent among U.S. drug-using offenders than Taiwanese drug-using offenders. Drug-using offenders in the U.S. also reported using a variety of different drugs and participating in multiple treatment programs. The major agents supplying illicit drugs were known dealers, and friends or acquaintances of U.S. and Taiwanese drug-using offenders, respectively. The article concludes that to effectively eliminate the problem of drug misuse, the Taiwanese government should focus on treatment instead of imprisonment, while the U.S. should target troubled teens and families.

Adult↗
PubMed2000

Magnolol stimulates steroidogenesis in rat adrenal cells.

1. This study investigated the effect of magnolol, a compound purified from Magnolia officinalis, on glucocorticoid production by primary adrenal cell culture. 2. Magnolol increased corticosterone secretion in a dose-dependent manner, this effect being maximal at 40 microM. A similar effect was seen in a minced adrenal gland system. 3. In magnolol-treated cells, the number and total area of cytoplasmic lipid droplets were reduced, suggesting a high utilization rate of cholesterol esters stored in lipid droplets. In control cells, the capsule of the lipid droplet was clearly delineated by immunostaining with antibody A2, whereas capsular staining was discontinuous or undetectable following magnolol treatment. The percentage of decapsulated cells increased significantly from 20% in the control group to 80% in the magnolol-treated group. 4. Magnolol-induced steroidogenesis was not mediated either via the traditional ACTH-cyclic AMP-protein kinase A pathway or by protein kinase C, since the intracellular cyclic AMP level did not change and inhibition of protein kinase A or C did not block the action of magnolol. Furthermore, calcium/calmodulin-dependent protein kinase II was not involved in magnolol-induced steroidogenesis. 5. The stimulatory effect of magnolol on steroidogenesis apparently requires new protein synthesis, since cycloheximide inhibited magnolol-induced corticosterone production by 50%. 6. Although other studies have shown that high concentrations of magnolol inhibit acyl-CoA: cholesterol acyltransferase and 11 beta-hydroxysteroid dehydrogenase in a cell-free system, our data show that, in adrenal cell cultures, low concentrations of magnolol have a stimulatory effect on steroidogenesis, and the glucocorticoid produced may explain the effective control of asthma by Magnolia officinalis.

Adrenal Glands↗
PubMed2000

Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic resonance angiography.

BACKGROUND AND PURPOSE: The purpose of the present study was to assess the diagnostic usefulness of early diffusion-weighted MRI (DWI) and MR angiography (MRA) in patients with ischemic stroke. Past approaches to stroke diagnosis required a series of diagnostic tests over several days of hospitalization. New magnetic resonance methodologies that include DWI and MRA may allow more rapid characterization of stroke pathophysiology. However, no previous study has assessed the impact on formal stroke subtype diagnosis of early imaging with DWI/MRA. METHODS: We analyzed 46 consecutive patients with acute ischemic stroke who underwent DWI/MRA within 24 hours of admission. Initial diagnoses were rendered with use of the 2 most widely used formal stroke subtype classification schemes, the TOAST and the Oxfordshire methods, which were applied to patients after CT/conventional MRI but before DWI/MRA. Modified TOAST and Oxfordshire diagnoses were then rendered based on the results of day 1 DWI, MRA, and DWI plus MRA. Final TOAST/Oxfordshire diagnoses at discharge were taken as the gold standard. RESULTS: Compared with final diagnoses, pre-MRI TOAST diagnoses matched final diagnoses in 48%, improving to 83% after DWI alone, 56% after MRA alone, and 94% after DWI plus MRA. For the TOAST diagnostic subtypes of large-vessel atherothromboembolism and small-vessel disease, pre-MRI diagnoses matched final diagnoses in 56% and 35% of patients, respectively, improving to 89% and 100% after DWI/MRA. Pre-MRI Oxfordshire diagnoses matched final diagnoses in 67% of patients, improving to 100% after DWI. CONCLUSIONS: The use of DWI/MRA within 24 hours of hospitalization substantially improves the accuracy of the diagnosis of early ischemic stroke subtype. When initial management and clinical trial eligibility decisions are influenced by stroke subtype, day 1 multimodal MRI is advantageous as a guide to therapy.

Female↗
PubMed1999

Anti-tumor-promoting activities of selected pungent phenolic substances present in ginger.

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has been widely used as a dietary spice, as well as in traditional oriental medicine. The rhizome of ginger contains pungent vanillyl ketones, including [6]-gingerol and [6]-paradol, and has been reported to possess a strong anti-inflammatory activity. These pungent substances have a vanilloid structure found in other chemopreventive phytochemicals, including curcumin. In our study, we found anti-tumor-promoting properties of [6]-gingerol and [6]-paradol. Thus, topical application of [6]-gingerol or [6]-paradol 30 min prior to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) attenuated the skin papillomagenesis initiated by 7,12-dimethylbenz[a]anthracene in female ICR mice. These substances also significantly inhibited the tumor-promoter-stimulated inflammation, TNF-alpha production, and activation of epidermal ornithine decarboxylase in mice. In another study, [6]-gingerol and [6]-paradol suppressed the superoxide production stimulated by TPA in differentiated HL-60 cells. Taken together, these findings suggest that pungent vanilloids found in ginger possess potential chemopreventive activities.

Animals↗
PubMed1998

Effects of a water-soluble extract of Cordyceps sinensis on steroidogenesis and capsular morphology of lipid droplets in cultured rat adrenocortical cells.

Cordyceps sinensis contains a factor that stimulates corticosteroid production in the animal model. However, it is not known whether this drug acts directly on the adrenal glands or indirectly via the hypothalamus-pituitary axis. In the present study, we used primary rat adrenal cell cultures to investigate the pharmacological function of a water-soluble extract of Cordyceps sinensis (CS) and the signaling pathway involved. Radioimmunoassay of corticosterone indicated that the amount of corticosterone produced by adrenal cells is increased in a positively dose-dependent manner by CS, reaching a maximum at 25 microg/ml. This stimulating effect was seen 1 h after CS treatment and was maintained for up to 24 h. Concomitantly, the lipid droplets in these cells became small and fewer in number. Immunostaining with a monoclonal antibody, A2, a specific marker for the lipid droplet capsule, demonstrated that detachment of the capsule from the lipid droplet occurs in response to CS application and that the period required for decapsulation is inversely related to the concentration of CS applied. The mechanism of CS-induced steroidogenesis is apparently different from that for ACTH, since intracellular cAMP levels were not increased in CS-treated cells. However, combined application with calphostin C, a PKC inhibitor, completely blocked the effect of CS on steroidogenesis, suggesting that activation of PKC may be responsible for the CS-induced steroidogenesis.

Adrenal Cortex↗
PubMed1997

Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects.

The effects of food and sucralfate on the pharmacokinetics of levofloxacin following the administration of a single 500-mg oral dose were investigated in a randomized, three-way crossover study with young healthy subjects (12 males and 12 females). Levofloxacin was administered under three conditions: fasting, fed (immediately after a standardized high-fat breakfast), and fasting with sucralfate given 2 h following the administration of levofloxacin. The concentrations of levofloxacin in plasma and urine were determined by high-pressure liquid chromatography. By noncompartmental methods, the maximum concentration of drug in serum (Cmax), the time to Cmax (Tmax), the area under the concentration-time curve (AUC), half-life (t1/2), clearance (CL/F), renal clearance (CLR), and cumulative amount of levofloxacin in urine (Ae) were estimated. The individual profiles of the drug concentration in plasma showed little difference among the three treatments. The only consistent effect of the coadministration of levofloxacin with a high-fat meal for most subjects was that levofloxacin absorption was delayed and Cmax was slightly reduced (Tmax, 1.0 and 2.0 h for fasting and fed conditions, respectively [P = 0.002]; Cmax, 5.9 +/- 1.3 and 5.1 +/- 0.9 microg/ml [90% confidence interval = 0.79 to 0.94] for fasting and fed conditions, respectively). Sucralfate, which was administered 2 h after the administration of levofloxacin, appeared to have no effect on levofloxacin's disposition compared with that under the fasting condition. Mean values of Cmax and AUC from time zero to infinity were 6.7 +/- 3.2 microg/ml and 47.9 +/- 8.4 microg x h/ml, respectively, following the administration of sucralfate compared to values of 5.9 +/- 1.3 microg/ml and 50.5 +/- 8.1 microg x h/ml, respectively, under fasting conditions. The mean t1/2, CL/F, CLR, and Ae values were similar among all three treatment groups. In conclusion, the absorption of levofloxacin was slightly delayed by food, although the overall bioavailability of levofloxacin following a high-fat meal was not altered. Finally, sucralfate did not alter the disposition of levofloxacin when sucralfate was given 2 h after the administration of the antibacterial agent, thus preventing a potential drug-drug interaction.

Adolescent↗
PubMed1997

Medical necessity for right heart catheterization.

Because there are no definitive guidelines for performing right heart catheterizations or controlled clinical trials demonstrating medical benefit, the value and necessity of performing routine right heart catheterizations for coronary artery disease have been questioned. This Texas Medical Foundation Health Care Quality Improvement Program project was designed to ensure medical necessity and proper documentation of right heart catheterization when performed as part of a bilateral procedure. Medicare claims data were used to identify Texas facilities where rates of bilateral catheterizations suggested that right heart catheterizations were being performed routinely. Five facilities were found to have rates of bilateral procedures exceeding 70%. Suggested guidelines for performing right heart catheterizations were prepared by the Texas Medical Association Committee on Cardiovascular Diseases. These guidelines, together with the facility's data on its rate of right heart catheterizations, were presented by the Texas Medical Foundation to the staff of each facility. They were asked to examine their individual facility's procedures for ensuring medical necessity and to develop and implement process improvement plans. Medicare claims data were analyzed to determine the rates of bilateral catheterizations before and after the plans were instituted. The statewide rate of bilateral procedures decreased from 27.2% to 21.3% (p < 0.005). Rate reductions for 4 facilities implementing improvement plans were statistically significant (p < 0.001): at the 1st facility, the rate decreased from 74.3% to 25.0%; at the 2nd, from 85.0% to 21.0%; at the 3rd, from 76.7% to 17.7%; and at the 4th facility, from 85.4% to 42.9%. The rate for the facility not implementing an improvement plan increased from 86.4% to 89.1%. Reductions in rates of bilateral procedures at the 4 facilities suggest that many procedures previously performed were routine and not medically indicated. Presentation of data and practice guidelines to facilities may have contributed to their ability to improve processes.

Cardiac Catheterization↗
PubMed1996

A protective anti-peptide antibody against the immunodominant site of the A24 Cruzeiro strain of foot-and-mouth disease virus and its reactivity with other subtype viruses containing the same minimum binding sequence.

A synthetic peptide vaccine of the general sequence Cys-Cys-(200-213)-Pro-Pro-Ser-(l41-158)-Pro-Cys-Gly(peptide A40), where the numbered residues refer to the VP1 sequence of foot-and-mouth disease virus (FMDV) strain A24 Cruzeiro, has previously been shown to elicit neutralizing and protective antibodies in guinea-pigs and cattle. To examine this immunogenic tract in more detail monoclonal antibodies (MAbs) were raised to this peptide. One such MAb C1.1, which recognized the homologous peptide, bound to native virus, neutralized infectivity in vitro and passively protected mice from challenge. Using overlapping dodecameric peptides the minimum binding 'footprint' of this MAb incorporated residues 149-154 which were respectively Gly-Ser-Leu-Ala-Ala-Arg. Since this 'footprint' occurs in several other A subtype strains of FMDV, the extent to which MAb C1.1 could cross-react was also examined. Using a liquid-phase competition ELISA, only viruses with a sequence that encompassed the same minimum binding 'footprint', namely A27 Cundinamarca Colombia/76, A Argentina/79, and A Venceslau Brazil/76 reacted with similar affinity against MAb C1.1. However, further serological examination of C1.1 with these viruses by indirect ELISA, in vitro neutralization and passive protection showed clear functional disparity. In contrast to the liquid-phase ELISA, the ability of C1.1 to react with electrostatically bound virus varied significantly depending on the subtype examined. Moreover, the capacity of this MAb to neutralize these subtypes showed wide divergence which was mirrored by the protection data.

Amino Acid Sequence↗
PubMed1995

The effects of recombinant human insulin-like growth factor (rhIGF)-1 and rhIGF-1/IGF binding protein-3 administration on rat osteopenia induced by ovariectomy with concomitant bilateral sciatic neurectomy.

We compared the effect of administration of recombinant human insulin-like growth factor-1 (rhIGF-1) alone or the rhIGF-1/IGF binding protein-3 (IGFBP-3) complex on osteopenia in rats. Female Sprague-Dawley rats (8 months old) underwent combined ovariectomy and bilateral sciatic neurectomy (OVX-NX) or sham operation only. After 2 months, the OVX-NX animals were injected subcutaneously with rhIGF-1 alone or with rhIGF-1A IGFBP-3 equimolar complex for 4 weeks. The IGF-1 contents and dose were 0.3 mg/kg of body weight (BW) three times/week, 3 mg/kg of BW once/week, or 3 mg/kg of BW three times /week. At the end of the experiment, the 4th and 5th lumbar vertebrae (L4, L5) and the proximal tibiae were removed after tetracycline labeling, and histomorphometrical analyses were performed on undecalcified sections using Villanueva's staining. The cancellous bone volume at L5 significantly increased by thickening of the trabecular width in rats treated with the complex. However, the increase in the values at the proximal tibia was not significant. The bone formation rates (BFR/BS) in the lumbar vertebrae of rats treated with the complex three times a week at doses of 0.3 mg/kg of BW and 3 mg/kg of BW were both significantly increased but the parameter increase was less marked with the dose of 3 mg/kg of BW once/week. The BFR/BS did not increase significantly in animals treated with IGF-1 alone. These findings clearly demonstrated that the effect of systemically administered rhIGF-1 on bone formation was markedly potentiated when combined with IGFBP-3 in estrogen deficiency combined with reduced activity. The action of IGF-1 was less potent on the bone in paralyzed limbs. The action of rhIGF-1/IGFBP-3 on trabecular bone appeared to depend not only on the dose but also on the frequency of administration and the parts of the skeleton in rats.

Analysis of Variance↗
PubMed1994

Purification of dopamine neurons by flow cytometry.

The heterogeneity and preponderence of other cell types present in cultures has greatly impeded our ability to study dopamine neurons. In this report, we describe methods for isolating nearly pure dopamine neurons for study in culture. To do so, the lipid-soluble dye, 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (diI) was injected into the embryonic rat striata where it was taken up by nerve terminals and transported overnight back to the innervating perikarya in the ventral midbrain. Midbrain cells were then dissected, dissociated and separated on the basis of their (rhodamine) fluorescence by flow cytometry. Nearly all cells recovered as fluorescent positive (> 98%) were also immunoreactive for the dopamine specific enzyme tyrosine hydroxylase (80%-96%). Little contamination by other cells types was observed after labeling for specific neuronal and glial markers. Purified dopamine neurons continued to thrive and elaborate neuronal processes for at least 3 days in culture. Using this new model, it may now be possible to directly study the cellular and molecular processes regulating the survival and functioning of developing, injured and transplanted dopamine neurons.

Animals↗
PubMed1988

Renal transport kinetics of chlorothiazide in the isolated perfused rat kidney.

The effect of protein binding on the renal excretion of chlorothiazide was examined in the isolated perfused rat kidney. Drug studies were performed in three rats at 6.00% bovine serum albumin + 0% dextran and in three rats at 0.25% bovine serum albumin + 3.83% dextran. Chlorothiazide was introduced into the recirculating perfusate at an initial concentration of 100 micrograms/ml, and was assayed using high-performance liquid chromatography. Functional viability of the kidney was assessed by measuring the fractional excretion of sodium and glucose, and the glomerular filtration rate. The protein binding of drug in perfusate was determined by equilibrium dialysis. These experimental conditions resulted in an approximate 14-fold increase of percent free (from 5.3-72.0%), and a 3-fold increase of renal (from 1.03-3.30 ml/min) and secretion (from 1.01-2.83 ml/min) clearances. The data were best fitted by a model in which one Michaelis-Menten term was used to describe active transport, and secretion was dependent upon free concentrations of chlorothiazide in the perfusate. The maximum velocity of secretion (Vm = 85.6 micrograms/min) and Michaelis constant (Km = 2.1 micrograms/ml) of chlorothiazide was estimated using a nonlinear least-squares regression program. These results suggest that for compounds of low renal extraction, free drug concentrations are the driving force for carrier-mediated tubular secretion.

Animals↗
PubMed1986

Renal transport kinetics of furosemide in the isolated perfused rat kidney.

Direct quantitative data and corresponding theory are provided for the effect of protein binding on the renal transport of furosemide. Drug studies were performed with various combinations of bovine serum albumin and dextran. This resulted in a percent unbound (fu) of furosemide ranging from 0.785 to 85.8%. The corrected renal (CLr/GFR) and secretion (CLs/GFR) clearances of furosemide were observed to increase with percent free, but in a nonproportional manner. Plots of CLr/GFR or CLs/GFR vs. fu appeared to have a prominent y intercept as well as a convex ascending curve. In addition, the excretion ratio [ER = CLr/(fu . GFR)] was reduced from 60.8 to 8.72 as fu increased. Overall, the data were best fitted to a model in which two Michaelis-Menten terms were used to describe renal tubular transport, and secretion was dependent upon free drug concentrations in the perfusate. The results demonstrate that the renal mechanisms of furosemide excretion are more complex than previously reported and that active secretion may involve two different transport systems over the concentration range studied.

Animals↗
PubMed1984

Grief work with substance abusers.

This article focuses on the implementation and outcome of a grief group study conducted with substance abusers. Group participants were chosen through a stratified random sampling from a residential drug and alcohol treatment facility. Control and experimental groups were used to test the efficacy of grief group therapy. Study results indicated that treatment group participants were significantly less depressed and better able to resolve painful feelings about their losses. The grief group approach is generic and can be modified to meet the needs of varied target groups. The distinctive approach and the empirical results both were completed by a clinician without disrupting the facility, patients or clinician's daily practices.

Adaptation, Psychological↗