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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 325 records · Page 18Linked to original sources

LDL isolated from Greek subjects on a typical diet or from American subjects on an oleate-supplemented diet induces less monocyte chemotaxis and adhesion when exposed to oxidative stress.

The mechanisms underlying the cardiovascular benefits of Mediterranean-style diets are not fully understood. The high content of monounsaturated fatty acids in Mediterranean-style diets derived from oleate-rich olive oil may be beneficial in reducing low density lipoprotein (LDL) oxidation and its subsequent development of atherogenic properties. This study sought to assess the proinflammatory potential of LDL isolated from subjects consuming a diet naturally rich in olive oil. LDL was isolated from 18 Greek, 18 American, and 11 Greek-Americans subjects, all of whom were living in the United States. Fatty acid composition and vitamin E levels of LDL were determined, as was the extent of copper-mediated LDL oxidation. LDL was also mildly oxidized by exposure to fibroblasts overexpressing 15-lipoxygenase and tested in vitro for bioactivity by determining its ability to stimulate monocyte chemotaxis and adhesion to endothelial cells. To confirm that dietary fatty acids influence the proinflammatory properties of mildly oxidized LDL, LDL was also isolated from 13 healthy American subjects after consumption of an 8-week liquid diet supplemented with either oleic (n=6) or linoleic (n=7) acid and tested for bioactivity in a similar fashion. There were no differences in the baseline lipid profiles among the Greeks, Americans, or Greek-Americans. Oleic acid content in LDL was 20% higher in the Greek compared with the American or Greek-American subjects (P<0.001). The extent of in vitro LDL oxidation, measured by conjugated diene formation, was lower in the Greek subjects (P<0.02), but there was no difference in the lag time. Induction of monocyte chemotaxis and adhesion by mildly oxidized LDL was decreased by 42% in the Greek group compared with the American subjects (P<0.001). There was an inverse correlation between the oleic acid content of LDL and stimulation of monocyte chemotaxis (r=-0.64, P<0.001) and a positive correlation between the polyunsaturated fatty acid content of LDL (total linoleate and arachidonic acids levels in LDL) and stimulation of monocyte chemotaxis (r=0.51, P<0.01) in the entire cohort. There were no differences in LDL vitamin E content between the groups. In the liquid-diet groups, the oleic acid-supplemented group had a 113% higher oleic acid content in LDL and a 46% lower linoleic acid content in LDL than the linoleate-supplemented group (P<0.001), whereas the vitamin E content in LDL was equal in both groups. When exposed to oxidative stress, the LDL enriched in oleic acid promoted less monocyte chemotaxis (52% lower) and reduced monocyte adhesion by 77% in comparison with linoleate-enriched LDL (P<0.001). There was a strong, negative correlation between oleic acid LDL content and monocyte adhesion (r=-0.73, P<0.001) and a strong, positive correlation between polyunsaturated fatty acid LDL content and monocyte adhesion (r=0.87, P<0.001). This study demonstrates that dietary enrichment of LDL with oleic acid is realistic and readily achieved by using diets currently in use in Mediterranean countries. In addition, these data suggest that LDL enriched with oleic acid and reduced in polyunsaturated fatty acids may be less easily converted to a proinflammatory, minimally modified LDL.

Cell Adhesion↗

All ApoB-containing lipoproteins induce monocyte chemotaxis and adhesion when minimally modified. Modulation of lipoprotein bioactivity by platelet-activating factor acetylhydrolase.

Mildly oxidized LDL has many proinflammatory properties, including the stimulation of monocyte chemotaxis and adhesion, that are important in the development of atherosclerosis. Although ApoB-containing lipoproteins other than LDL may enter the artery wall and undergo oxidation, very little is known regarding their proinflammatory potential. LDL, IDL, VLDL, postprandial remnant particles, and chylomicrons were mildly oxidized by fibroblasts overexpressing 15-lipoxygenase (15-LO) and tested for their ability to stimulate monocyte chemotaxis and adhesion to endothelial cells. When conditioned on 15-LO cells, LDL, IDL, but not VLDL increased monocyte chemotaxis and adhesion approximately 4-fold. Chylomicrons and postprandial remnant particles were also bioactive. Although chylomicrons had a high 18:1/18:2 ratio, similar to that of VLDL, and should presumably be less susceptible to oxidation, they contained (in contrast to VLDL) essentially no platelet-activating factor acetylhydrolase (PAF-AH) activity. Because PAF-AH activity of lipoproteins may be reduced in vivo by oxidation or glycation, LDL, IDL, and VLDL were treated in vitro to reduce PAF-AH activity and then conditioned on 15-lipoxygenase cells. All 3 PAF-AH-depleted lipoproteins, including VLDL, exhibited increased stimulation of monocyte chemotaxis and adhesion. In a similar manner, lipoproteins from Japanese subjects with a deficiency of plasma PAF-AH activity were also markedly more bioactive, and stimulated monocyte adhesion nearly 2-fold compared with lipoproteins from Japanese control subjects with normal plasma PAF-AH. For each lipoprotein, bioactivity resided in the lipid fraction and monocyte adhesion could be blocked by PAF-receptor antagonists. These data suggest that the susceptibility of plasma lipoproteins to develop proinflammatory activity is in part related to their 18:1/18:2 ratio and PAF-AH activity, and that bioactive phospholipids similar to PAF are generated during oxidation of each lipoprotein. Moreover, LDL, IDL, postprandial remnant particles, and chylomicrons and PAF-AH-depleted VLDL all give rise to proinflammatory lipids when mildly oxidized.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Development and evaluation of a pilot program to promote exercise among mothers of preschool children.

The health benefits of physical activity are well documented, but mothers of young children experience significant barriers to exercise. A 10-week minimal-intervention exercise program, involving a weekly meeting at which child care was provided, and guidance in establishing independent exercise was developed on the basis of previous research with this population group. Thirty-two women with children under age 5, and in the contemplation or preparation stages of exercise behavior change, were recruited from Australian play groups. Postprogram measures showed small but significant decreases in body mass index, resting heart rate, and diastolic blood pressure. Three months later, 41% of participants were still active. Family-related constraints were highly disruptive to these participants. This study is limited by its small sample size, lack of controls, and potential biases in recruitment and assessment, but it does suggest that hard-to-reach groups, such as mothers of young children, may be mobilized to exercise if programs explicitly address social contexts and the constraints on individual choice.

Journal Article↗

Transforming growth factor-beta1-induced proliferation of the prostate cancer cell line, TSU-Pr1: the role of platelet-derived growth factor.

The results of our previous study revealed that transforming growth factor-beta1 (TGFbeta1) stimulated proliferation of the prostate cancer cell line, TSU-Pr1. This observation is unexpected, for TGFbeta usually inhibits proliferation in prostate cancer cells. The present study examines possible mechanisms through which TGFbeta1 induces this proliferation. We postulate that TGFbeta1 action is mediated through an indirect mechanism by inducing the expression of platelet-derived growth factor (PDGF), which, in turn, stimulates proliferation. The TGFbeta1-induced proliferation can be abrogated by treatment with a PDGF-neutralizing antibody. Treatment with exogenous PDGF significantly increased TSU-Pr1 proliferation. Finally, treatment of TSU-Pr1 cells with TGFbeta1 resulted in an increase in PDGF secretion. These results indicate that TGFbeta1-induced proliferation in TSU-Pr1 cells is at least mediated through an increased secretion of PDGF.

Becaplermin↗

Psychological stress and disordered eating: an exploratory study with young Australian women.

An exploratory study was conducted to examine whether the relationships between psychological stress and disordered eating, reported in many studies using American samples, would be found in a sample of young Australian women. A total of 212 women aged 18-22 years completed a questionnaire assessing a number of women's health issues, including life events stress, perceived stress levels, psychological distress, disordered eating behaviours, and concerns about weight and eating. While results showed few strong relationships between stress and eating variables for the sample overall, those women with high psychological stress levels appeared to be more likely to engage in disordered eating behaviours than women with low levels of stress. Results suggest that further investigation, targeting subgroups of women scoring highly on measures of psychological stress or disordered eating, may help clarify our understanding of the relationships between these factors in young Australian women.

Adolescent↗

Biomass conversion to mixed alcohol fuels using the MixAlco process.

The MixAlco process is a patented technology that converts any biodegradable material (e.g., sorted municipal solid waste, sewage sludge, industrial biosludge, manure, agricultural residues, energy crops) into mixed alcohol fuels containing predominantly 2-propanol, but also higher alcohols up to 7-tridecanol. The feedstock is treated with lime to increase its digestibility. Then, it is fed to a fermentor in which a mixed culture of acid-forming microorganisms produces carboxylic acids. Calcium carbonate is added to the fermentor to neutralize the acids to their corresponding carboxylate salt. The dilute (approximately 3%) carboxylate salts are concentrated to 19% using an amine solvent that selectively extracts water. Drying is completed using multi-effect evaporators. Finally, the dry salts are thermally converted to ketones which subsequently are hydrogenated to alcohols. All the steps in the MixAlco process have been proven at the laboratory scale. A techno-economic model of the process indicates that with the tipping fees available in New York (126 dollars/dry tonne), mixed alcohol fuels may be sold for 0.04 dollars/L (0.16 dollars/gal) with a 60% return on investment (ROI). With the average tipping fee in the United States rates (63 dollars/dry tonne), mixed alcohol fuels may be sold for 0.18 dollars/L (0.69 dollars/gal) with a 15% ROI. In the case of sugarcane bagasse, which may be obtained for about 26 dollars/dry ton, mixed alcohol fuels may be sold for 0.29 dollars/L (1.09 dollars/gal) with a 15% ROI.

Journal Article↗

UV irradiation of pig metaphase chromosomes: maturation-promoting factor degradation, nuclear cytology and cell cycle progression.

Experiments were designed to test two hypotheses. The first was that irradiation of pig metaphase chromosomes would block the normal sequence of cytological and molecular events associated with activation; the second postulated that damaged DNA would prevent eggs from progressing through the first mitotic cleavage cycle. The experimental protocol involved selectively irradiating the metaphase II plate of pig oocytes with highly focused 254 nm ultraviolet (UV) light, followed by activation using standard electroactivation procedures. The following assessments were made of different groups of eggs: (i) nuclear membrane reassembly; (ii) chromosomal cytology; (iii) changes in maturation-promoting factor kinase (MPF kinase) activity at 1 h intervals after activation; and (iv) mitotic progression of eggs containing damaged chromosomal fragments. UV irradiation neither prevented the reassembly of nuclear membranes required for pronuclear formation nor interfered with the normal pattern of MPF kinase degradation after egg activation. UV irradiation did induce a wide range of chromatin defects, including condensation and dispersal of DNA fragments which, in turn, resulted in the formation of micronuclei in the treated eggs and embryos. The presence of damaged DNA retarded, but did not inhibit, progression through the first mitotic cycle. No evidence was obtained that the subsequent mitotic cycle was adversely affected by the presence of UV-damaged DNA. Overall, these results indicate that early cleavage divisions in pig eggs are not blocked by the presence of damaged, hypercondensed chromatin. In this respect, pig eggs are similar to Xenopus eggs, but are different from bovine eggs. On the basis of these findings it is suggested that focused UV irradiation offers a simple and rapid technique for the non-invasive enucleation of pig oocytes provided that the residual hypercondensed chromatin does not affect later developmental stages.

Analysis of Variance↗

Epinephrine-induced arrhythmias: effects of thoracic epidural anesthesia and vagotomy during enflurane anesthesia in rabbits.

For evaluating the effects of thoracic epidural anesthesia, with or without bilateral vagotomy, epinephrine-induced arrhythmias were studied in 31 rabbits anesthetized with 1 minimum alveolar concentration of enflurane. We divided the rabbits into 5 groups: Group I (epidural saline as control group; n=6), Group II (epidural lidocaine without vagotomy; n=6), Group III (intravenous lidocaine; n=7), Group IV (epidural saline with vagotomy; n=6), and Group V (epidural lidocaine with vagotomy; n=6). Using logdose protocol, epinephrine was infused at an initial rate of 0.67 microg/kg/min and increased by Exp[0.4] until arrhythmias occurred; if arrhythmias occurred at any of these doses, a smaller dose, divided by Exp[0.2], was tested. Arrhythmic dose of epinephrine was defined as the smallest infusion rate needed to produce four or more arrhythmias within 15 sec during epinephrine infusion. Arrhythmic dose of epinephrine and its plasma concentration in epidural lidocaine group were significantly higher than control (p<0.05). Similarity of results was also noted amongst the intravenous lidocaine group, vagotomy only group, and vagotomized epidural lidocaine group with respect to the control. These results suggest that thoracic epidural anesthesia raises the threshold for enflurane-epinephrine induced arrhythmias in rabbits and that this effect is eliminated by bilateral vagotomy.

Anesthesia, Epidural↗

Prospective evaluation of perinatal risk factors for cerebral palsy and delayed development in high risk infants.

Prematurity, intrauterine infection and perinatal brain injury have been reported to be significant risk factors of cerebral palsy (CP). We examined the perinatal predictors of cerebral palsy and delayed development (DD) in 184 high risk infants. Thirty-five infants were diagnosed as cerebral palsy and delayed development at 12 months corrected age. Antenatal, intrapartum, and neonatal factors were prospectively evaluated in 2 groups of high risk infants compared with controls; Group A (n = 79), infants weighing less than 2,000 g; Group B (n = 43), infants weighing 2,000 g or more. In univariate analysis, there were no significant antenatal and intrapartum factors associated with cerebral palsy and delayed development in either group. We found that significant postnatal risk factors of CP in group A included sepsis (p = 0.008), BPD (bronchopulmonary dysplasia) (p = 0.028), IVH (intraventricular hemorrhage) (p = 0.042), ventriculomegaly (VM) (p = 0.001) and a longer duration of mechanical ventilation (p = 0.001); while in group B, sepsis (p = 0.047) and neonatal seizure (p = 0.027) were significant risk factors. In multivariate analysis, sepsis in group B was a moderate risk factor of CP (OR (odds ratio) 1.47; 95% CI (confidence interval) 1.02-2.13). In conclusion, neonatal sepsis may contribute to the development of cerebral palsy and delayed development. We suggest that high risk infants who have sepsis should be carefully followed for cerebral palsy and delayed development. The prevention of cerebral palsy may be feasible by decreasing neonatal risk factors such as sepsis during the neonatal period.

Cerebral Palsy↗

Reactivation of neurocysticercosis: case report.

A 37-year-old woman with a known history of longstanding neurocysticercosis presented with a three-day history of new onset headache. Several years prior to her current presentation, she had undergone cysticidal treatment and was assumed to be cured of active disease. Computed tomography and magnetic resonance imaging studies done three months prior to presentation showed multiple intracerebral calcified lesions consistent with resolved neurocysticercosis. Physical and laboratory findings were noncontributory. Imaging studies showed the same previously calcified lesions, but they were now surrounded by large amounts of edema. This case represents a unique report of reactivation of neurocysticercosis and raises interesting questions about the natural history of this infection.

Adult↗

The role of corticosteroids in the treatment of cerebral schistosomiasis caused by Schistosoma mansoni: case report and discussion.

A 26-year-old Brazilian man was admitted to The Toronto Hospital with a headache and visual scintillation. His last travel to Brazil was five years previously. A computed tomography (CT) scan of the head showed an occipital mass with surrounding vasogenic edema. Occipital brain biopsy revealed Schistosoma mansoni eggs. The patient was treated with two doses of praziquantel (20 mg/kg) and dexamethasone (10 mg). His symptoms and occipital mass resolved. Cerebral schistosomiasis is, in part, caused by the host's inflammatory response to Schistosoma. Modes of treatment have included surgical resection, the antiparasitic drugs oxamniquine or praziquantel, and corticosteroids. Corticosteroids may diminish granulomatous inflammation, thereby preventing further tissue destruction, and there is evidence that they also reduce ova deposition. Our review of the literature supports prompt medical therapy in patients with cerebral schistosomiasis. While the minimally or asymptomatic individual may be treated with praziquantel alone, clinicians should consider adjunctive therapy with corticosteroids for patients with prominent neurologic signs or symptoms or mass lesions with evidence of surrounding edema on a CT scan or by magnetic resonance imaging.

Adult↗

Reversible biventricular dysfunction secondary to ischemia in a patient with acute airway obstruction: a case report and review of the literature on reversible causes of acute ventricular dysfunction.

Reversible causes of acute myocardial dysfunction are important for clinicians to recognize. Reversible biventricular dysfunction secondary to myocardial ischemia is presented in a patient with acute upper airway obstruction. The differential diagnosis of reversible acute myocardial dysfunction is reviewed.

Acute Disease↗

Symptomatic forearm muscle hernia: repair by autologous fascia lata inlay.

Eleven cases of symptomatic muscle hernias of the forearm requiring surgical intervention have been described previously. Pain on extremity exertion and an unaesthetic bulge of the forearm were the primary indications for surgery. Advocated treatment modalities range from forearm fasciotomy to anatomic repair of the fascial defect. Although fasciotomy relieves the narrow fascial constriction around the herniated muscle reliably, it often yields an unappealing forearm deformity and incomplete resolution of pain on extremity exertion. Anatomic repair provides the theoretical advantage of restoring normal muscle fascia relationships while concomitantly improving the aesthetic appearance of the extremity. The authors report a case of symptomatic forearm muscle herniation treated successfully with an autologous fascia lata inlay graft.

Adult↗

Lack of mechanism-based inactivation of rat hepatic microsomal cytochromes P450 by doxorubicin.

Administration of the antineoplastic doxorubicin to rodents causes depression of hepatic cytochrome P450 (CYP) dependent biotransformation, an effect that has been partially attributed to the ability of doxorubicin to stimulate microsomal lipid peroxidation. Since doxorubicin can be bioactivated by the CYP/NADPH-CYP reductase system to products that bind covalently to microsomal protein, we hypothesized that doxorubicin functions as a mechanism-based inactivator of hepatic microsomal CYPs and (or) NADPH-CYP reductase under conditions in which doxorubicin-stimulated NADPH-dependent lipid peroxidation is minimized. In vitro studies were conducted with hepatic microsomes isolated from untreated and phenobarbital-treated male rats. Unlike the positive control carbon tetrachloride, doxorubicin (10 microM) did not stimulate NADPH-dependent lipid peroxidation in microsomal incubations containing EDTA (1.5 mM). Doxorubicin did not cause NADPH-dependent loss of microsomal CYP, heme, or steroid hydroxylation activities selective for CYP2A, CYP2B, CYP2C11, and CYP3A. The positive control 1-aminobenzotriazole caused marked NADPH-dependent decreases in all of these parameters. Neither doxorubicin nor 1-aminobenzotriazole caused NADPH-dependent loss of NADPH-CYP reductase activity, and neither compound altered the immunoreactive protein levels of CYP2B, CYP2C11, CYP3A, and NADPH-CYP reductase. These results indicate that a pharmacologically relevant concentration of doxorubicin does not cause direct mechanism-based inactivation of hepatic microsomal CYPs or NADPH-CYP reductase, suggesting that the ability of doxorubicin to depress hepatic CYP-mediated biotransformation in vivo is due to lipid peroxidation mediated heme destruction, altered heme metabolism, and (or) decreased expression of selected CYP enzymes.

Animals↗

Retinal detachment in postpartum preeclampsia and eclampsia: report of two cases.

Retinal detachment is an unusual complication of hypertensive disorder in pregnancy. It has been reported in 1% to 2% of patients with severe preeclampsia and in 10% of patients with eclampsia. Choroidal ischemia may be the cause of retinal detachment. We know that mild arteriolar spasm involving the bulbar conjunctival vessels has been observed in the normal pregnancy, but in pregnancy-induced hypertension the vasospasm may be severe and result in choroidal ischemia. Most patients with retinal detachment in pregnancy-induced hypertension have had full spontaneous resolution within a few weeks, and they did not have any sequelae. Medical treatment with antihypertensive drugs and steroids may be helpful. We report two rare cases of retinal detachment and persistent hypertension in association with postpartum eclampsia and post-cesarean section preeclampsia. These patients had normotension throughout pregnancy. Preeclampsia or eclampsia developed after delivery, and blurred vision, headache, and reduced vision accompanied serous retinal detachment. The serous retinal detachment disappeared within 3 weeks. Good outcomes were found in the follow-up examinations in both of these cases. For women who had been normotensive at the time of delivery and then complained in the postpartum period of blurred vision, headaches, nausea and vomiting, we should consider the possibility of retinal detachment and perform fundoscopy.

Adult↗