Biomedical subjects

P Lau

Publications and source records attributed to P Lau.

At least 37 records · Page 2Linked to original sources

PubMed2000

Parental history of alcoholism and problem behaviors in Native-American children and adolescents.

BACKGROUND: A positive family history of alcoholism is one of the most consistent and powerful predictors of a person's risk for developing this disorder. This finding has stimulated much research on etiological vulnerability factors and mechanisms by which children of alcoholic parents are at high risk for developing alcohol-related problems. In primarily Euro-American samples, parental alcoholism has been associated with a variety of negative outcomes for children and adolescents, including problematic behavior. Native-American Indians, in addition to high rates of alcoholism and alcohol-related mortality, have the highest prevalence of a positive family history for alcoholism of all ethnic groups in the United States. METHODS: This study used the Achenbach Child Behavior Checklist (CBCL) to evaluate behavioral problems in 96 Mission Indian children and adolescents based on the presence or absence of parental alcohol dependence and sex of the offspring. RESULTS: Consistent with previous research, results indicated a high prevalence of a positive family history of alcoholism in these Native-American youths. Seventy-four percent of the offspring had either one or both parents with alcohol dependence (children of alcoholics). Only 7% had no first- or second-degree alcoholic relatives. Results indicated that sons of alcoholics scored significantly higher on the Total Behavior Problem scale, as well as the Internalizing and Externalizing scales, of the CBCL than sons of nonalcoholics, whereas there were no significant differences in CBCL scores between daughters of alcoholics and daughters of nonalcoholics. It is noteworthy that scores on the CBCL for Mission Indian children of alcoholics were comparable to scores in the published literature of children of alcoholics of other ethnicities. In addition, a relatively low percentage of youths were identified with significant levels of behavioral problems. CONCLUSIONS: These findings suggest that sons of alcoholics of Mission Indian heritage experience more problems than sons of nonalcoholics, but also suggest that Mission Indian children of alcoholics are not more vulnerable to behavioral problems than children of alcoholic parents of other ethnic backgrounds.

Adolescent↗

PubMed1999

Use of beta-blocker therapy in older patients after acute myocardial infarction in Ontario.

BACKGROUND: Despite its proven efficacy, beta-blocker therapy remains underused in elderly patients after myocardial infarction (MI). The objectives of this study were to identify undertreated groups of seniors and to determine whether older and frailer patients are being selectively dispensed low-dose beta-blocker therapy. METHODS: From a comprehensive hospital discharge database, all people aged 66 years or more in Ontario who survived an acute MI between April 1993 and March 1995 were identified and classified into those who did not receive beta-blocker therapy and those dispensed low, standard or high doses of this agent. Logistic regression models were used to study the effect of age, sex, comorbidity, potential contraindications to beta-blocker therapy and residence in a long-term-care facility on the odds of not being dispensed a beta-blocker. Among beta-blocker users, the odds of being dispensed low relative to standard or high doses of this agent were evaluated. RESULTS: Of the 15,542 patients, 7549 (48.6%) were not dispensed a beta-blocker. Patients 85 years of age or more were at greater risk of not receiving beta-blocker therapy (adjusted odds ratio [OR] 2.8, 95% confidence interval [CI] 2.5-3.2) than were those 66 to 74 years. Having a Charlson comorbidity index of 3 or greater was associated with an increased risk of not receiving beta-blocker therapy (adjusted OR 1.5, 95% CI 1.3-1.8) compared with having lower comorbidity scores. Patients who resided in a long-term-care facility were at increased risk of not being prescribed beta-blocker therapy (adjusted OR 2.6, 95% CI 2.0-3.4). Among the 5453 patients with no identifiable contraindication to beta-blocker therapy, women were significantly less likely than men to receive this agent (p = 0.005). Of the 6074 patients who received beta-blockers, 2248 (37.0%) were dispensed low-dose therapy. Patients aged 85 years or more had an increased risk of being dispensed low-dose therapy (adjusted OR 1.6, 95% CI 1.3-2.0) compared with those aged 66 to 74 years. Compared with those who had the lowest comorbidity scores, patients with the highest comorbidity scores were more likely to be dispensed low-dose beta-blocker therapy (adjusted OR 1.3, 95% CI 1.0-1.8). INTERPRETATION: Almost half of Ontario patients aged 66 or more who survived an MI, particularly those who were older or frailer, did not receive beta-blocker therapy. Among those dispensed beta-blocker therapy, older and frailer patients were more frequently dispensed low-dose therapy.

Adrenergic Antagonists↗

PubMed1999

Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD.

ROR/RZR is an orphan nuclear receptor that has no known ligand in the 'classical sense'. In the present study we demonstrate that RORalpha is constitutively expressed during the differentiation of proliferating myoblasts to post-mitotic multinucleated myotubes, that have acquired a contractile phenotype. Exogenous expression of dominant negative RORalpha1DeltaE mRNA in myogenic cells significantly reduces the endogenous expression of RORalpha1 mRNA, represses the accumu-lation and delays the activation of mRNAs encoding MyoD and myogenin [the muscle-specific basic helix-loop-helix (bHLH) proteins] and p21(Waf-1/Cip-1) (a cdk inhibitor). Immunohistochemistry demonstrates that morpho-logical differentiation is delayed in cells expressing the RORDeltaE transcript. Furthermore, the size and development of mutlinucleated myotubes is impaired. The E region of RORalpha1 interacts with p300, a cofactor that functions as a coactivator in nuclear receptor and MyoD-mediated transactivation. Consistent with the functional role of RORalpha1 in myogenesis, we observed that RORalpha1 directly interacts with the bHLH protein MyoD. This interaction was mediated by the N-terminal activation domain of the bHLH protein, MyoD, and the RORalpha1 DNA binding domain/C region. Furthermore, we demonstrated that p300, RORalpha1 and MyoD interact in a non-competitive manner. In conclusion, this study provides evidence for a biological role and positive influence of RORalpha1 in the cascade of events involved in the activation of myogenic-specific markers and cell cycle regulators and suggests that crosstalk between theretinoid-relatedorphan (ROR) nuclear receptors and the myogenic bHLH proteins has functional consequences for differentiation.

Antigens, Differentiation↗

PubMed1999

Long-term functional outcome and quality of life after stapled restorative proctocolectomy.

OBJECTIVE: To evaluate prospectively long-term quality of life and functional outcome after restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis, and to evaluate and validate a novel quality-of-life indicator in this group of patients. SUMMARY BACKGROUND DATA: Restorative proctocolectomy with ileal pouch-anal anastomosis is now the preferred option when total proctocolectomy is required for ulcerative colitis or familial adenomatous polyposis, but long-term data on functional outcome and quality of life after the procedure are lacking. METHODS: Patients (n = 977) who underwent RPC with stapled anastomosis for colitis or polyposis coli and who were followed for > or =12 months were included. Quality of life, fecal incontinence, and satisfaction with surgery were prospectively evaluated by structured interview or questionnaire for 1 to 12 years after surgery (median 5.0). Quality of life was scored using the Cleveland Global Quality of Life (CGQL) instrument (Fazio Score). This is a novel score developed over the past 15 years by the senior author. Quality of life was also evaluated in a subgroup of patients with the Short Form 36 (SF-36). The CGQL was validated by determining its reliability, responsiveness, and validity as well as its correlation with the SF-36 score. RESULTS: Postoperative quality of life as measured by SF-36 was excellent and compared well with published norms for the general U.S. population. The CGQL was found to be reliable, responsive, and valid, and there was a high correlation with the SF-36 scores. Using the CGQL, quality of life was shown to increase after the first 2 years after surgery, and there was no deterioration thereafter. The prevalence of perfect continence increased from 75.5% before surgery to 82.4% after surgery, and although this deteriorated somewhat >2 years after surgery, it was no worse than preoperative values. Ninety-eight percent of patients would recommend the surgery to others. CONCLUSIONS: Long-term quality of life after ileal pouch surgery is excellent and the level of continence is satisfactory. This surgery is an excellent long-term option in patients requiring total proctocolectomy. The CGQL is a simple, valid, and reliable measure of quality of life after pelvic pouch surgery and may well be applicable in many other clinical conditions.

Aged↗

PubMed1999

Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose.

OBJECTIVES: Low-dose drug therapy is promoted as a way to maximize benefit and minimize adverse drug effects when prescribing for older adults. This population-based study evaluates the age and sex-related use of two common therapies: thiazide diuretics, where evidence supports the use of low-dose therapy, and beta-blockers, where trials have not evaluated the minimum effective dose. DESIGN: Using linked administrative databases we identified all of the 120,613 persons dispensed a thiazide diuretic therapy and 12,908 myocardial infarction survivors dispensed beta-blocker therapy in Canada's largest province. We used logistic regression models to study the association of age and sex with dispensing of low-dose thiazide diuretic and beta-blocker therapy at doses lower than evaluated in trials. RESULTS: Of 120,613 older people dispensed a thiazide diuretic, 32,372 (26.8%) were dispensed a low dose. Patients 85 years of age or older, relative to the youngest group, were 30% more likely to be dispensed low-dose therapy (OR=1.31; 95% CI, 1.27 to 1.36; P < .001). Women were 8% more likely than men to be dispensed a low-dose thiazide diuretic (OR=1.08; 95% CI, 1.05 to 1.11; P < .001). Of 10,991 myocardial infarction survivors dispensed atenolol, metoprolol, propranolol, or timolol, 9458 (86.1%) were dispensed a lower-than-evaluated dose. Patients 85 years of age or older, relative to those in the youngest group, were more than twice as likely to be dispensed a lower-than-evaluated beta-blocker therapy dose (OR=2.28; 95% CI, 1.74 to 3.04; P < .001). No difference was noted in the use of beta-blocker therapy dose by sex (OR=1.0; 95% CI, .89 to 1.15; P = .95). CONCLUSIONS: Low-dose thiazide diuretic therapy prescribed widely to older people, particularly those of advanced age and women. The vast majority of myocardial infarction survivors were dispensed beta-blocker therapy at lower-than-evaluated doses. These findings highlight the need to manufacture low-dose thiazide diuretic therapy and to evaluate the minimum effective dose of beta-blocker therapy.

Adrenergic beta-Antagonists↗

PubMed1999

The nuclear receptor corepressor N-CoR regulates differentiation: N-CoR directly interacts with MyoD.

Classical ligand-activated nuclear receptors (e.g. thyroid hormone receptor, retinoic acid receptor), orphan nuclear receptors (e.g. Rev-erbAalpha/beta), Mad/Max bHLH (basic helix loop helix)-LZ proteins, and oncoproteins, PLZF and LAZ3/BCL6, bind DNA and silence transcription by recruiting a repressor complex that contains N-CoR (nuclear receptor corepressor)/SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), Sin3A/B, and HDAc-1/-2 proteins. The function of the corepressor, N-CoR, in the process of cellular differentiation and coupled phenotypic acquisition, has not been investigated. We examined the functional role of N-CoR in myogenesis (muscle differentiation), an ideal paradigm for the analysis of the determinative events that govern the cell's decision to divide or differentiate. We observed that the mRNA encoding N-CoR was suppressed as proliferating myoblasts exited the cell cycle, and formed morphologically and biochemically differentiated myotubes. Exogenous expression of N-CoR (but not RIP13) in myogenic cells ablated 1) myogenic differentiation, 2) the expression of the myoD gene family that encode the myogenic specific bHLH proteins, and 3) the crucial cell cycle regulator, p21Waf-1/Cip-1 mRNA. Furthermore, N-CoR expression efficiently inhibits the myoD-mediated myogenic conversion of pluripotential C3H10T1/2 cells. We demonstrate that MyoD-mediated transactivation and activity are repressed by N-CoR. The mechanism involves direct interactions between MyoD and N-CoR; moreover, the interaction was dependent on the amino-terminal repression domain (RD1) of N-CoR and the bHLH region of MyoD. Trichostatin A treatment significantly stimulated the activity of MyoD by approximately 10-fold and inhibited the ability of N-CoR to repress MyoD-mediated transactivation, consistent with the involvement of the corepressor and the recruitment of a histone deacteylase activity in the process. This work demonstrates that the corepressor N-CoR is a key regulator of MyoD activity and mammalian differentiation, and that N-CoR has a multifaceted role in myogenesis.

Animals↗

PubMed1998

Drosophila nerve cord culture: a tool for studying neural development.

The culture of explanted neural tissues has been a useful tool for the study of cellular and molecular neurobiology in vertebrates. We have developed a technique for the culture of explanted ventral nerve cords from Drosophila embryos. We have examined the morphology and dynamic behaviour of the growth cones that extend from these nerve cords, and the effect of calcium deprivation on the bundling of axons that are regenerated from the explanted tissue. This technique offers a unique opportunity to combine in vitro techniques for neuronal cell culture with the powerful techniques of genetic analysis that are available with Drosophila.

Animals↗

PubMed1998

Relationship of adipose tissue cholesteryl ester transfer protein (CETP) mRNA to plasma concentrations of CETP in man.

Adipose tissue is an important site of cholesteryl ester transfer protein (CETP) synthesis and CETP plays a local role in adipocyte cholesteryl ester accumulation from high density lipoproteins (HDL). Human adipose tissue maintained in organ culture secretes CETP, but it is not known to what extent adipose tissue CETP contributes to the plasma pool of CETP in man. Aging is associated with changes in adipose tissue composition and function, including impaired adipocyte triglyceride lipolysis. We determined pericardiac adipose tissue CETP mRNA levels and plasma concentrations of CETP and lipoproteins in middle-aged and elderly subjects (47-78 years) with stable coronary heart disease (CHD) undergoing elective coronary artery bypass grafting (CABG). Plasma concentrations of CETP were highly correlated with adipose tissue CETP mRNA abundance (r = 0.85, P < 0.002, n = 13), suggesting that adipose tissue may contribute to the plasma pool of CETP. There was an inverse correlation between age and plasma CETP concentrations in this population (r = -0.70, P <0.008, n = 13). CETP mRNA levels in pericardial adipose tissue were also negatively associated with age (r = -0.70, P < 0.035, n = 10). These relationships were independent of plasma lipids, lipoproteins and body mass index. However, adipose tissue CETP mRNA concentrations levels were related to adipocyte size. CETP mRNA abundance in pericardial adipose tissue was negatively correlated with mean adipocyte size, estimated as adipose tissue triglyceride/mg protein (r = -0.76, P < 0.02, n = 9), in accord with previous studies from this laboratory demonstrating that CETP gene expression is greatest in small lipid-poor adipocytes. A negative relationship between age and adipose tissue CETP mRNA abundance (r = -0.63, P < 0.05, n = 10) was confirmed in a separate population of healthy female subjects, aged 18-63 years, from whom subcutaneous adipose tissue was obtained at the time of reduction mammoplasty. The decrease in plasma concentrations of CETP with age may be explained in part by changes in adipose tissue CETP gene expression.

Adipocytes↗

PubMed1997

Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesteryl esters by human adipose tissue.

We have determined the role of cholesteryl ester transfer protein (CETP) in selective uptake of high density lipoprotein (HDL)-derived cholesteryl esters (CE) by human adipose tissue, using organ culture or collagenase-digested adipocytes. Incubation of the fresh tissue fragments with HDL containing [3H]CE or 125I-apoprotein (apo) A-I resulted in significant uptake of HDL-CE-derived label. Addition of recombinant CETP (rCETP) increased CE uptake in a dose-response fashion. In contrast, little association of 125I-apoA-I with adipose tissue was noted, and addition of rCETP did not alter apoA-I uptake or degradation. Incubation of adipose tissue with TP2, an anti-CETP monoclonal antibody, which inhibits neutral lipid transfer, markedly reduced selective uptake of HDL-CE. Studies using human adipocytes isolated by collagenase digestion also demonstrated selective uptake of HDL-CE and enhancement of this process by rCETP. To confirm that the association of HDL-CE-derived radioactivity with adipose tissue was not due to neutral lipid exchange between adipocytes and HDL, we measured changes in HDL composition following incubation of HDL and rCETP with isolated adipocytes. A decrease in HDL-CE concentration in the medium was observed, an effect which was markedly attenuated when incubations were carried out in the presence of monoclonal antibody TP2. Furthermore, the decrease in HDL-CE was accompanied by an increase in HDL free cholesterol, likely representing efflux of adipocyte cholesterol to HDL. There were no significant changes in phospholipid, apoA-I, or apoA-II in the medium following incubation with adipocytes. These data demonstrate a novel and important role for CETP in selective uptake of HDL-cholesteryl esters by human adipocytes and suggest that this pathway may be of quantitative physiological significance in HDL remodeling and adipocyte cholesterol accumulation.

Adipocytes↗

PubMed1997

The carboxyl-terminal sequence of the human secretory mucin, MUC6. Analysis Of the primary amino acid sequence.

The distribution of MUC6 suggests that its primary function is protection of vulnerable epithelial surfaces from damaging effects of constant exposure to a wide range of endogenous caustic or proteolytic agents. A combination of genomic, cDNA. and 3' rapid amplification of cDNA ends techniques was used to isolate the carboxyl-terminal end of MUC6. The 3' nontandem repeat region contained 1083 base pairs of coding sequence (361 amino acids) followed by 632 base pairs of 3'-untranslated region. The coding sequence consists of two distinct regions; region 1 contained the initial 270 amino acids (62% Ser-Thr-Pro with no Cys residues), and region 2 contained the COOH-terminal 91 amino acids (22% Ser-Thr-Pro with 12% Cys). Although region 1 had no homology to any sequences in GenBank, region 2 had approximately 25% amino acid homology to the COOH-terminal regions of human mucins MUC2, -5, and -5B and von Willebrand factor. The shortness of region 2 would leave little of the peptide backbone exposed to a potentially hostile environment. Antibody studies suggest that MUC6 in its native form exists as a disulfide-bonded multimer. The conservation of the 11 cysteine positions in region 2 suggests the importance of this short region to mucin polymerization.

Amino Acid Sequence↗

PubMed1997

Specificity of lumbar medial branch and L5 dorsal ramus blocks. A computed tomography study.

STUDY DESIGN: A cross-sectional study. OBJECTIVES: To determine the face validity of lumbar medial branch blocks. SUMMARY OF BACKGROUND DATA: Lumbar medial branch blocks have been used increasingly to diagnose zygapophysial joint pain. The course and relations of the medial branches of the dorsal rami have been demonstrated in previous anatomic studies. What is not known is whether blocks of the medial branches anesthetize these nerves exclusively or whether they anesthetize other structures that are potential sources of pain. METHODS: In a cadaveric study, the branches of the dorsal rami were exposed. Spinal needles were placed over the nerves, and plain radiographs were taken to demonstrate the precise radiographic locations of the nerves. In the second phase of the study, healthy volunteers underwent injections of radiographic contrast over the nerves, and plain radiographs and computed tomographic images were taken. Injections were performed using different rates of injection and in two positions for each nerve. RESULTS: Radiographic contrast incorporated the medial branches of the dorsal rami in every injection. When injections were performed using the upper position, aberrant flow of contrast medium was demonstrated with extension into the epidural space or intervertebral foramina. When a position lower on the transverse process was selected, aberrant flow was very uncommon. Eight percent of injections were found to be intravenous. CONCLUSIONS: When the appropriate technique is used, medial branch blocks are target specific. To guard against false-negative responses due to intravenous up-take, contrast medium must be used before the injection of local anaesthetic.

Adult↗

PubMed1997

Acute epididymitis in boys: are antibiotics indicated?

OBJECTIVES: To report the results of using supportive therapy only, rather than antibiotics, in managing boys with acute sterile epididymitis. PATIENTS AND METHODS: From 1991 to 1995, 48 boys presented with acute epididymitis. The diagnosis was confirmed by radionuclide scan in 43 cases, ultrasonography in one, surgical exploration in one and physical examination in three. Urine was collected for microscopy and culture: if pyuria was detected, antibiotics were prescribed. If the urine analysis was normal, the patient was advised to minimize physical activity and analgesics were prescribed. RESULTS: Of the 48 boys, five (10%) had pyuria; seven patients with either no urine tested or negative urine culture were given antibiotics. The remaining 36 were managed with supportive therapy only. The mean follow-up was 87 days (with three patients lost to follow-up). No boys showed any evidence of testicular atrophy or other complications. CONCLUSION: Only a minority of boys with acute epididymitis, as defined by increased flow on radionuclide scanning of the scrotum, have a bacterial aetiology. For those without pyuria or positive urine culture, the condition is self-limiting and does not lead to testicular atrophy. We recommend that for boys with acute epididymitis who have no urinary abnormalities, antibiotics are not indicated. The aetiology of acute sterile epididymitis in boys remains obscure.

Acute Disease↗

PubMed1997

Plasma kinetics of cholesteryl ester transfer protein in the rabbit. Effects of dietary cholesterol.

The plasma kinetics of recombinant human cholesteryl ester transfer protein (rCETP) were studied in six rabbits before and after cholesterol feeding (0.5% wt/wt). The rCETP, labeled with the use of the Bolton Hunter reagent, was shown to retain neutral lipid transfer activity. After intravenous infusion, labeled rCETP associated with rabbit lipoproteins to an extent similar to endogenous rabbit CETP (62% to 64% HDL associated). The plasma kinetics of CETP, modeled with the use of SAAM-II, conformed to a two-pool model, likely representing free and loosely HDL-associated CETP (fast pool) and a tightly apo (apolipoprotein) AI-associated (slow pool) CETP. The plasma residency time (chow diet) of the fast pool averaged 7.1 hours and of the slow pool, 76.3 hours. The production rate (PR) into and the fractional catabolic rate (FCR) of the fast pool were 20 and 10 times the PR and FCR, respectively, of the slow pool. In response to cholesterol feeding, CETP PR, FCR, and plasma mass increased by 416%, 60%, and 230%, respectively. There was a strong correlation (r = .95, P = .003) between the increase in rabbit plasma CETP and the modeled increase in CETP PR in response to cholesterol feeding, suggesting that labeled human rCETP is a satisfactory tracer for rabbit plasma CETP. CETP is catabolized by distinct pools, likely corresponding to an apo AI-associated (slow) pool and a free and/or loosely HDL-associated (fast) pool. Factors that alter the affinity of CETP for HDL would be predicted to result in altered CETP catabolism. The effect of dietary cholesterol on plasma CETP mass can be explained largely by the effects on CETP synthesis, consistent with the observed effects of cholesterol on tissue mRNA levels.

Animals↗

PubMed1996

Phaeochromocytoma in pregnancy.

The Royal Women's Hospital, Melbourne, is a tertiary referral hospital with over 7,000 deliveries per year. We report 3 cases of phaeochromocytoma in pregnancy at the hospital in the 20-year period since 1976. The first case was unsuspected and resulted in a maternal death. The subsequent 2 cases were diagnosed antenatally with successful outcomes for both mother and baby. The 3 cases demonstrate the importance of an early antenatal diagnosis and the special management problems of phaeochromocytoma in pregnancy. The diagnosis of phaeochromocytoma should be considered in any pregnant women with severe hypertension, particularly if presenting before 20 weeks' gestation, labile, or associated with sweating, palpitations or headaches.

Adrenal Gland Neoplasms↗

PubMed1996

Operative laparoscopic management of adnexal cysts: initial experience at the Royal Women's Hospital 1991-1994.

The introduction of operative laparoscopic surgery for benign adnexal cysts had led to shorter postoperative hospitalization (mean stay of 2.0 days) in association with a low rate of major complications (1.6%). A planned laparoscopic approach was successful in 95.2% (179/188) of patients. The majority of women were premenopausal (93.6%) and the most common procedure performed was an ovarian cystectomy (73.5% of cysts). Three ovarian cysts that were thought to be benign by preoperative and intraoperative assessment were subsequently found to be ovarian tumours of low malignant potential after histological examination. Operative laparoscopy has become the preferred mode of treatment for benign adnexal cysts at the Royal Women's Hospital. It confers a wide range of benefits to patients, reduces health-care costs and appears to be a safe and effective treatment modality.

Adolescent↗

PubMed1996

Role of Lp A-I and Lp A-I/A-II in cholesteryl ester transfer protein-mediated neutral lipid transfer. Studies in normal subjects and in hypertriglyceridemic patients before and after fenofibrate therapy.

The two major subclasses of HDL contain apo A-I only (Lp A-I) or both apo A-I and apo A-II (Lp A-I/A-II). We have carried out experiments to quantify the participation of Lp A-I and Lp A-I/A-II in the neutral lipid transfer reaction in normal and hypertriglyceridemic subjects. Thirteen hypertriglyceridemic subjects were studied before and after fenofibrate therapy. Fenofibrate treatment resulted in decreases in total cholesterol, triglycerides (TG), and VLDL cholesterol of 19%, 48%, and 70%, respectively, and a 28% increase in HDL cholesterol, with no significant change in the proportion of Lp A-I and Lp A-I/A-II particles. The abundance of cholesteryl ester transfer protein (CETP) mRNA in peripheral adipose tissue decreased with treatment in four of five patients studied; however, no change occurred in plasma CETP mass. Using an isotopic transfer assay, we demonstrated that both Lp A-I and Lp A-I/A-II participated in the CE transfer reaction, with no change after fenofibrate therapy. This finding suggests that the marked increase in HDL cholesterol during fenofibrate therapy is due to normalization of plasma TG and hence decreased opportunity for mass transfer of lipid between HDL and TG-rich proteins in vivo. In this population of hypertriglyceridemic subjects, CETP was distributed in both the Lp A-I and Lp A-I/A-II subfractions of HDL, with preferential association with the smaller Lp A-I poor. In contrast, in nine normal subjects studied, negligible amounts of CETP were associated with Lp A-I/A-II. Nonetheless, the Lp A-I/A-II fraction of HDL contributed significantly to total CE mass transfer in normolipidemic plasma. Lp A-I/A-II is an efficient donor for CE transfer to TG-rich lipoproteins, and its low affinity for CETP may in fact facilitate neutral lipid transfer either by a shuttle mechanism or by formation of a ternary complex.

Adult↗

PubMed1996

Opening the pleura during internal mammary artery harvesting: advantages and disadvantages.

OBJECTIVE: To evaluate the findings of previous studies that opening of the pleura during internal mammary artery (IMA) dissection might be an important factor in increasing the operative morbidity. DESIGN: A randomized control trial. SETTING: A university hospital. PATIENTS: Two hundred and eighty consecutive patients with no significant pulmonary disease. INTERVENTION: Harvesting of the IMA with (130 patients) or without (150 patients) opening the pleura. MAIN OUTCOME MEASURES: Comparison of the incidence of pleural effusion, cardiac tamponade, postoperative respiratory complications and the hospital stay. RESULTS: Pleural effusion occurred more often in the patients who had opening of the pleura (20% versus 5%); however, none of the patients required tapping. Postoperative bleeding with cardiac tamponade occurred in five patients in the closed pleura group. Six patients in the open pleura group had postoperative bleeding but without tamponade. The average postoperative stay was 7 days for both groups. No significant differences were recorded in postoperative respiratory complications. CONCLUSIONS: Opening of the pleura during IMA harvesting does not increase the operative morbidity. It may have other advantages and is recommended in most cases of IMA harvesting.

Female↗

PubMed1996

Apolipoprotein B mRNA editing protein: a tool for dissecting lipoprotein metabolism and a potential therapeutic gene for hypercholesterolemia.

Apolipoprotein (apo) B mRNA editing protein is an essential catalytic component of the apoB mRNA editing enzyme complex. Its cDNA has been cloned recently from rats and humans. In the presence of other proteins of the editing enzyme complex, it will deaminate nucleotide 6666 in apoB mRNA, a cytidine residue, converting it to uridine. The end result of this reaction is the production of apoB-48 in place of apoB-100. The editing protein exists as a homodimer. It imparts editing activity to HepG2, a human hepatoma cell line, causing these cells to start producing apoB-48 in addition to apoB-100. Therefore, it can be used as a therapeutic agent to reduce apoB-100 production. Preliminary experiments in our laboratory indicate that somatic gene transfer of the editing protein is highly effective in lowering plasma low density lipoproteins.

APOBEC-1 Deaminase↗