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Biomedical subjects

E Lin

Publications and source records attributed to E Lin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Regulation of the 75-kDa subunit of mitochondrial complex I by iron.

Iron homeostasis is tightly regulated, as cells work to conserve this essential but potentially toxic metal. The translation of many iron proteins is controlled by the binding of two cytoplasmic proteins, iron regulatory protein 1 and 2 (IRP1 and IRP2) to stem loop structures, known as iron-responsive elements (IREs), found in the untranslated regions of their mRNAs. In short, when iron is depleted, IRP1 or IRP2 bind IREs; this decreases the synthesis of proteins involved in iron storage and mitochondrial metabolism (e.g. ferritin and mitochondrial aconitase) and increases the synthesis of those involved in iron uptake (e.g. transferrin receptor). It is likely that more iron-containing proteins have IREs and that other IRPs may exist. One obvious place to search is in Complex I of the mitochondrial respiratory chain, which contains at least 6 iron-sulfur (Fe-S) subunits. Interestingly, in idiopathic Parkinson's disease, iron homeostasis is altered, and Complex I activity is diminished. These findings led us to investigate whether iron status affects the Fe-S subunits of Complex I. We found that the protein levels of the 75-kDa subunit of Complex I were modulated by levels of iron in the cell, whereas mRNA levels were minimally changed. Isolation of a clone of the 75-kDa Fe-S subunit with a more complete 5'-untranslated region sequence revealed a novel IRE-like stem loop sequence. RNA-protein gel shift assays demonstrated that a specific cytoplasmic protein bound the novel IRE and that the binding of the protein was affected by iron status. Western blot analysis and supershift assays showed that this cytosolic protein is neither IRP1 nor IRP2. In addition, ferritin IRE was able to compete for binding with this putative IRP. These results suggest that the 75-kDa Fe-S subunit of mitochondrial Complex I may be regulated by a novel IRE-IRP system.

5' Untranslated Regions↗
PubMed2001

Bioavailability of amiodarone tablets administered with and without food in healthy subjects.

The tablet form of amiodarone is indicated for the treatment of recurrent ventricular fibrillation or hemodynamically unstable ventricular tachycardia. It is recommended that the tablet be taken with meals in cases of gastrointestinal intolerance. However, the effect of food on its bioavailability is unknown. The primary objective of this study was to determine the effect of food on the bioavailability of amiodarone. This was a 2-period crossover study conducted in 30 healthy male subjects. Subjects were randomly assigned to 1 of 2 sequences in which the following 2 treatments were administered: (1) a single-dose of amiodarone (three 200-mg Cordarone tablets) after an overnight fast, and (2) the same dose immediately after a standard high-fat breakfast. Plasma concentrations of amiodarone and desethylamiodarone (DEA) were measured for 6 weeks after each dose. Food enhanced the extent of absorption, resulting in a peak concentration (Cmax) and area under the curve (AUCT) 3.8 and 2.4 times the respective values under fasting conditions. Food also significantly increased the rate of absorption, reducing the time (tmax) to Cmax from 7.1 to 4.5 hours. The effect of food on DEA levels was significant but less pronounced. An in vitro dissolution study confirmed a marked difference between amiodarone release under simulated fed and fasting conditions. Thus, food significantly enhances both the rate and extent of absorption of amiodarone, which is attributed partially to the effect of food on drug release from its formulation. Therefore, it is recommended that amiodarone tablets be taken consistently with meals.

Adult↗
PubMed2001

A randomized trial of relapse prevention of depression in primary care.

BACKGROUND: Despite high rates of relapse and recurrence, few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment. We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care. METHODS: Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were randomized to a relapse prevention program (n = 194) or usual primary care (n = 192). Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aimed at enhancing adherence to antidepressant medication, recognition of prodromal symptoms, monitoring of symptoms, and development of a written relapse prevention plan. Follow-up assessments were completed at 3, 6, 9, and 12 months by a telephone survey team blinded to randomization status. RESULTS: Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls. Intervention patients had significantly fewer depressive symptoms, but not fewer episodes of relapse/recurrence over the 12-month follow-up period. CONCLUSIONS: A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes.

Adolescent↗
PubMed2001

The effects of glucocorticoid therapy on inflammatory responses to coronary artery bypass graft surgery.

HYPOTHESIS: Delayed or reduced polymorphonuclear leukocyte (PMN) apoptosis may contribute to prolongation of systemic inflammation after cardiopulmonary bypass. BACKGROUND/OBJECTIVE: Preoperative administration of glucocorticoids has been used ostensibly to attenuate the systemic inflammation associated with cardiopulmonary bypass. Therefore, this study evaluated, in patients undergoing cardiopulmonary bypass, the efficacy of glucocorticoids in restoring peripheral blood PMN apoptosis and modulating PMN surface receptors (CD95, tumor necrosis factor receptor [TNFR]) known to be involved in proapoptotic or antiapoptotic signal transduction. DESIGN: Randomized control study. SETTING: Medical school and affiliated tertiary care hospital. PATIENTS: Thirteen patients undergoing coronary artery bypass grafting. INTERVENTION: Patients were randomly assigned to the control group (n = 7) or to receive 1 g of methylprednisolone sodium succinate on anesthetic induction (n = 6). MAIN OUTCOME MEASURES: Blood samples were drawn before induction, 20 minutes after sternotomy and bypass, immediately postoperatively, and on postoperative day 1. Isolated PMNs were incubated for 6 hours with or without the CD95 agonist CH 11. Polymorphonuclear leukocyte apoptosis was measured using propidium iodide-RNAase staining and flow cytometry. Levels of PMN cell-associated receptors (TNFR and CD95), cytokines (TNF-alpha, interleukin 6 [IL-6], IL-8, and IL-10), and soluble receptors (sTNFR1 and sTNFR2) were measured. RESULTS: In all 13 patients, spontaneous and Fas-mediated PMN apoptosis decreased more than 80% from baseline (P<.001) by postoperative day 1. Polymorphonuclear leukocyte CD95 increased (P<.003) by postoperative day 1 compared with baseline, whereas PMN TNFR was unchanged. Methylprednisolone administration did not modulate PMN apoptosis or immunocyte receptor expression; however, such treatment did decrease postoperative IL-6 secretion (P<.001) and increase postoperative IL-10 secretion (P<.001). CONCLUSIONS: The complications of major surgery include persistent inflammation, which can lead to multisystem organ failure. Polymorphonuclear leukocyte resistance to apoptosis may contribute to this process. A single preoperative dose of glucocorticoids did not effect PMN apoptosis or receptor phenotype.

Anti-Inflammatory Agents↗
PubMed2001

Structural characterization of the oxidative degradation products of an antifungal agent SCH 56592 by LC-NMR and LC-MS.

LC-NMR and LC-MS were used to characterize the structures of four major degradation products of SCH 56592, an antifungal drug candidate in clinical trials. These compounds were formed under stress conditions in which the bulk drug substance was heated in air at 150 degrees C for 12 days, and were separated from SCH 56592 as a mixture using a semi-preparative HPLC method. The data from LC-NMR, LC-ESI-MS (electrospray ionization mass spectrometry) and LC-ESI-MS/MS indicate that the oxidation occurred at the piperazine ring in the center of the drug molecule. The structures of the degradation products were determined from the 1H NMR spectra obtained via LC-NMR, which were supported by LC-ESI-MS and LC-ESI-MS/MS analyses. A novel degradation pathway of SCH 56592 was proposed based on these characterized structures.

Antifungal Agents↗
PubMed2001

Plasma aluminum levels during sucralfate prophylaxis for stress ulceration in critically ill patients on continuous venovenous hemofiltration: a randomized, controlled trial.

OBJECTIVE: To investigate plasma aluminum levels in critically ill patients requiring continuous venovenous hemofiltration (CVVH), while receiving sucralfate for stress ulcer prophylaxis. DESIGN: Randomized, controlled study. SETTING: Cardiothoracic intensive care unit. PATIENTS: Twenty postoperative cardiac surgical patients INTERVENTIONS: Twenty patients requiring CVVH support for acute renal failure were randomized into two groups for concurrent stress ulcer prophylaxis. Group 1 (n = 10) received nasogastric sucralfate, and group 2 patients received intravenous ranitidine. Plasma aluminum samples were analyzed at baseline and on days 1, 4, 8, and 14. MEASUREMENTS AND MAIN RESULTS: In both the sucralfate and ranitidine groups, clinical characteristics, number of days the patients were on CVVH support (median, 5.5 [range, 2-32] days, and median, 3 [range, 2-18] days, respectively) and duration of prophylaxis (median, 12 [range, 4-42] days, and median, 16 [range, 3-62] days, respectively) were similar. There were no significant differences in the baseline aluminum concentrations (median, 0.37 [range, 0.15-1.63] micromol/L, vs. median, 0.32 [range, 0.11-1.0] micromol/L; p =.79). On initiation of therapy, aluminum levels in the sucralfate group increased dramatically on day 1 (median, 0.87 [range, 0.26-4.4] micromol/L) and peaked on day 4 (median, 2.84 [range, 1.52-4.44] micromol/L) with seven of the ten patients exhibiting levels of >2 micromol/L. In the ranitidine group, there were no significant elevations in aluminum levels above baseline. Analysis of the two groups at the four time points revealed that aluminum levels in the sucralfate group were up to 14 times higher, with the confidence intervals suggesting that the true value may be 2-27 times higher (p <.0001). On cessation of CVVH, a rapid decline in aluminum levels was observed. No clinical manifestations of these potentially toxic levels were observed. CONCLUSIONS: The use of sucralfate for stress ulcer prophylaxis in patients requiring CVVH results in toxic elevations in plasma aluminum levels. Alternative agents should be considered for prophylaxis in these patients.

Acute Kidney Injury↗
PubMed2001

Childhood abuse and lifetime psychopathology in a community sample.

OBJECTIVE: The authors assessed lifetime psychopathology in a general population sample and compared the rates of five psychiatric disorder categories between those who reported a childhood history of either physical or sexual abuse and those who did not. METHOD: A modified version of the Composite International Diagnostic Interview and a self-completed questionnaire on child abuse were administered to a probability sample (N=7,016) of Ontario residents 15 to 64 years of age. RESULTS: Those reporting a history of childhood physical abuse had significantly higher lifetime rates of anxiety disorders, alcohol abuse/dependence, and antisocial behavior and were more likely to have one or more disorders than were those without such a history. Women, but not men, with a history of physical abuse had significantly higher lifetime rates of major depression and illicit drug abuse/dependence than did women with no such history. A history of childhood sexual abuse was also associated with higher rates of all disorders considered in women. In men, the prevalence of disorders tended to be higher among those who reported exposure to sexual abuse, but only the associations with alcohol abuse/dependence and the category of one or more disorders reached statistical significance. The relationship between a childhood history of physical abuse and lifetime psychopathology varied significantly by gender for all categories except for anxiety disorders. Although not statistically significant, a similar relationship was seen between childhood history of sexual abuse and lifetime psychopathology. CONCLUSIONS: A history of abuse in childhood increases the likelihood of lifetime psychopathology; this association appears stronger for women than men.

Adolescent↗
PubMed2001

Comparisons of men with full or partial eating disorders, men without eating disorders, and women with eating disorders in the community.

OBJECTIVE: The authors compared 62 men who met all or most of the DSM-III-R criteria for eating disorders with 212 women who had similar eating disorders and 3,769 men who had no eating disorders on a wide variety of clinical and historical variables. METHOD: The groups of subjects were derived from a community epidemiologic survey performed in the province of Ontario that used the World Health Organization's Composite International Diagnostic Interview. RESULTS: Men with eating disorders were very similar to women with eating disorders on most variables. Men with eating disorders showed higher rates of psychiatric comorbidity and more psychosocial morbidity than men without eating disorders. CONCLUSIONS: These results confirm the clinical similarities between men with eating disorders and women with eating disorders. They also reveal that both groups suffer similar psychosocial morbidity. Men with eating disorders show a wide range of differences from men without eating disorders; the extent to which these differences are effects of the illness or possible risk factors for the occurrence of these illnesses in men is not clear.

Adolescent↗
PubMed2001

Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon.

After birth, the full-term ductus arteriosus actively constricts and undergoes extensive histologic changes that prevent subsequent reopening. These changes are thought to occur only if a region of intense hypoxia develops within the ductus wall after the initial active constriction. In preterm infants, indomethacin-induced constriction of the ductus is often transient and is followed by reopening. Prostaglandins and nitric oxide both play a role in inhibiting ductus closure in vitro. We hypothesized that combined inhibition of both prostaglandin and nitric oxide production (with indomethacin and N-nitro-L-arginine (L-NA), respectively) may be required to produce the degree of functional closure that is needed to cause intense hypoxia. We used preterm (0.67 gestation) newborn baboons that were mechanically ventilated for 6 d: 6 received indomethacin alone, 7 received indomethacin plus L-NA, and 16 received no treatment (control). Just before necropsy, only 25% of control ductus and 33% of indomethacin-treated ductus were closed on Doppler examination; in contrast, 100% of the indomethacin-plus-L-NA-treated ductus were closed. Control and indomethacin-treated baboons developed negligible-to-mild ductus hypoxia (EF5 technique). Similarly, there was minimal evidence of ductus remodeling. In contrast, indomethacin-plus-L-NA-treated baboons developed intense hypoxia in regions where the ductus was most constricted. The hypoxic muscle strongly expressed vascular endothelial growth factor, and proliferating luminal endothelial cells filled and occluded the lumen. In addition, cells in the most hypoxic regions were undergoing DNA fragmentation. In conclusion, preterm newborns are capable of remodeling their ductus, just like the full-term newborn, if they can reduce their luminal blood flow to a point that produces intense ductus wall hypoxia. Combined prostaglandin and nitric oxide inhibition may be necessary to produce permanent closure of the ductus and prevent reopening in preterm infants.

Animals↗
PubMed2001

Impact of normative feedback on problem drinkers: a small-area population study.

OBJECTIVE: As many as one in four adults in North America experiences some problems due to alcohol consumption. Although most of these problem drinkers do not have concerns that are severe enough to merit formal treatment, such drinking has large economic costs and can place the drinker at risk for long-term negative health and social consequences. The present study evaluated a minimal intervention that used normative feedback about population drinking to motivate changes in alcohol use. METHOD: An intervention pamphlet was mailed to over 6,000 households in Toronto, randomized by block from a region containing almost 10,000 households. In the month after the mailing, a general population survey was conducted in the region to assess alcohol use. RESULTS: Respondents from households receiving normative feedback (n = 472) reported significantly lower alcohol use than controls (n = 225), but this effect occurred only among respondents who met an objective criterion for problem drinking and who perceived some risk associated with their drinking. CONCLUSIONS: Viewed from a public health perspective, normative feedback interventions have the potential for a significant payoff because they can be provided at low cost and to problem drinkers who might ordinarily never access any treatment services.

Adult↗
PubMed2001

Surge of anti-SS-A antibody associated with fulminant thrombotic thrombocytopenic purpura in pregnancy.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon clinical syndrome and is rarely associated with systemic lupus erythematosus (SLE). Diagnosis of TTP in patients with SLE, especially those who are pregnant, is challenging. We report the case of a pregnant woman with a high level of anti-SS-A antibody (162,143 U/mL) and fulminant TTP. The patient responded to plasma exchange treatment. Recent studies indicate that patients with SLE and another serologic abnormality, such as the presence of antiphospholipid antibody, may be at high risk for TTP. We explore the possible pathogenesis of acute TTP in patients with SLE and summarize the risk factors for acute TTP in patients with SLE and the current treatments for SLE-associated TTP.

Adult↗
PubMed2000

Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine.

Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate addicts stabilized on buprenorphine showed no evidence of precipitated opiate withdrawal after s.l. buprenorphine-naloxone combinations. Buprenorphine and naloxone bioavailability was approximately 40 and 10%, respectively. Intravenous buprenorphine and naloxone produced subjective effects similar to those of s.l. buprenorphine and did not precipitate opiate withdrawal.

Administration, Sublingual↗
PubMed2000

The Drosophila RAD21 cohesin persists at the centromere region in mitosis.

'Cohesin' is a highly conserved multiprotein complex thought to be the primary effector of sister-chromatid cohesion in all eukaryotes. Cohesin complexes in budding yeast hold sister chromatids together from S phase until anaphase, but in metazoans, cohesin proteins dissociate from chromosomes and redistribute into the whole cell volume during prophase, well before sister chromatids separate (reviewed in [1,2]). Here we address this apparent anomaly by investigating the cell-cycle dynamics of DRAD21, the Drosophila orthologue of the Xenopus XRAD21 and Saccharomyces cerevisiae Scc1p/Mcd1p cohesins [3]. Analysis of DRAD21 in S2 Drosophila tissue culture cells and live embryos expressing a DRAD21-green fluorescent protein (GFP) fusion revealed the presence of four distinct subcellular pools of DRAD21: a cytoplasmic pool; a chromosome-associated pool which dissociates from chromatin as chromosomes condense in prophase; a short-lived centrosome-associated pool present during metaphase-anaphase; and a centromere-proximal pool which remains bound to condensed chromosomes, is found along the junction of sister chromatids between kinetochores, and persists until the metaphase-anaphase transition. We conclude that in Drosophila, and possibly all metazoans, a minor pool of cohesin remains bound to centromere-proximal chromatin after prophase and maintains sister-chromatid cohesion until the metaphase-anaphase transition.

Animals↗
PubMed2000

Drad21, a Drosophila rad21 homologue expressed in S-phase cells.

Cohesin is an evolutionarily conserved multiprotein complex required to establish and maintain sister chromatid cohesion. Here, we report the cloning and initial characterization of the Drosophila homologue of the fission yeast rad21 cohesin subunit, called Drad21. The Drad21 coding region was localized to centromeric heterochromatin and encodes a 715 amino acid (aa) protein with 42% aa identity to vertebrate Rad21p-homologues, 25% with Scc1p/Mcd1p (S. cerevisiae) and 28% with Rad21p (S. pombe). Sequences with similarity to the sites of proteolytic cleavage identified in Scc1p/Mcd1p are not evident in DRAD21. Northern blot and mRNA in-situ studies show that Drad21 is developmentally regulated, with high levels of expression in early embryogenesis, in S-phase cells of proliferating imaginal tissues, and in the early endocycling cells of the embryonic gut.

Amino Acid Sequence↗
PubMed2000

Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands.

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.

Adolescent↗
PubMed2000

Analysis of the measurement precision of arterial lumen and wall areas using high-resolution MRI.

High-resolution MRI may be used to monitor the progression of human carotid atherosclerosis by measuring the lumen and wall area changes over time. The purpose of this study was to analyze the precision of quantitative measurements of lumen and wall areas. Two independent MR scans near the carotid bifurcation were conducted on eight patients within 2 weeks. The error of lumen area measurement was 6. 2%, 9.2%, and 9.7% for T(1), proton density, and T(2)-weighted images, respectively, and the error of wall area measurement was 10. 8%, 10.9%, and 12.0%. The precision of area measurement correlates strongly with image quality.

Algorithms↗
PubMed2000

Vocal fold physiology.

This article examines the physiologic factors responsible for the production of phonation in humans. The article begins with an explanation of the control mechanisms of phonation and theories of vocal fold vibration. The physiologic concepts are based on the myoelastic-aerodynamic, body-cover, and mucosal wave theories. An evaluation of the cover-body theory is explained in terms of pitch control. The factors that regulate the vocal folds to produce pitch changes, intensity variation, and register effects are outlined. The changes in pitch, intensity, and voice qualities are related to the vocal fold mass, tension, subglottic pressure, and airflow generated by the phonatory systems. A brief summary of abnormal voice production is given in terms of disordered physiology and the emerging theory of chaos.

Biomechanical Phenomena↗