Biomedical subjects

G S Ginsburg

Publications and source records attributed to G S Ginsburg.

At least 19 recordsLinked to original sources

PubMed2001

Gender differences in exercise-induced changes in sex hormone levels and lipid peroxidation in athletes participating in the Hawaii Ironman triathlon. Ginsburg-gender and exercise-induced lipid peroxidation.

BACKGROUND: Exercise reduces the risk of coronary heart disease in men and women but paradoxically, may promote free-radical formation, lipid peroxidation and vascular tissue injury. In this study, we assessed whether exercise-induced oxidative stress similarly affected men and women who participated in the Hawaii Ironman triathlon. METHODS AND RESULTS: Fifty-seven athletes (38 males) who completed the triathlon (3.9 km swim, 180.2 km bike, 42.2 km run) participated in this study. Blood samples were obtained 2 days before and immediately after the triathlon for the measurement of lipids, antioxidants and sex hormones and for the assessment of the susceptibility of plasma lipids to peroxidation. Lipid changes after exercise were similar for men and women. However, the susceptibility of plasma lipids to peroxidation was reduced by 61% (P < 0.001) in men and only 14% (P = NS) in women postrace. These changes were not associated with the supplemental use or levels of antioxidants. In addition, in men there was an increase of 58% in the antioxidant sex hormone estradiol and a decrease of 58% in testosterone (P < 0.001) postrace. No significant changes were noted for these two hormones in women. CONCLUSIONS: There are significant gender-specific differences in the susceptibility of lipids to peroxidation and in changes in estradiol and testosterone levels as a result of ultra-endurance exercise. These changes may in part explain the salutary effect of exercise on the development of vascular disease.

Adult↗

PubMed2001

Personalized medicine: revolutionizing drug discovery and patient care.

Advances in human genome research are opening the door to a new paradigm for practising medicine that promises to transform healthcare. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual's molecular profile, will impact the way drugs are developed and medicine is practiced. Knowledge of the molecular basis of disease will lead to novel target identification, toxicogenomic markers to screen compounds and improved selection of clinical trial patients, which will fundamentally change the pharmaceutical industry. The traditional linear process of drug discovery and development will be replaced by an integrated and heuristic approach. In addition, patient care will be revolutionized through the use of novel molecular predisposition, screening, diagnostic, prognostic, pharmacogenomic and monitoring markers. Although numerous challenges will need to be met to make personalized medicine a reality, with time, this approach will replace the traditional trial-and-error practice of medicine.

Drug Design↗

PubMed2001

Psychostimulants in preschool children with attention-deficit/hyperactivity disorder: clinical evidence from a developmental disorders institution.

OBJECTIVE: To examine psychostimulant response in preschool children with attention-deficit/hyperactivity disorder (ADHD) in an outpatient child psychiatry clinic (housed within a developmental disorders institution) over 3, 12, and 24 months of treatment. METHOD: A systematic retrospective chart review was conducted for 27 preschool children with ADHD who were started on psychostimulants between the ages of 3 and 5 years, inclusive. Two child and adolescent psychiatrists reviewed each chart independently, using the Clinical Global Impressions (CGI) scale to rate the severity of illness and global improvement and the Side Effects Rating Form to rate side effects. RESULTS: Over 24 months, psychostimulants were stopped in three children (11%) because of side effects and concomitant psychotropic medications were added in seven children (26%). The CGI severity-of-illness ratings showed a significant effect of time over 3, 12, and 24 months of psychostimulant treatment (all p values < .0001). Rate of response was 74% at 3 months and 70% at 12 and 24 months. Side effects were mostly mild and occurred in 63% of the children at 3 months, 41% at 12 months, and 29% at 24 months. CONCLUSIONS: The findings suggest that preschool children with developmental disorders respond to psychostimulants but need close monitoring because of frequent side effects. Inasmuch as the study participants were recruited from a child psychiatry clinic housed within a developmental disorders institution and had a high rate of developmental disorders, the findings may not generalize to other preschool children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Atherosclerosis: a cancer of the blood vessels?

A series of molecular pathways have in common a significant role in the pathogenesis and progression of atherosclerosis and cancer. Shared mechanisms implicated for both diseases include oxidative stress and the cellular damage that results from it, toxic metabolites produced by cigarette smoking, and increased dietary fat intake. Atherosclerosis may begin when an injury or infection mutates or transforms a single arterial smooth muscle cell in the progenitor of a proliferative clone, similar to the most widely held carcinogenesis theory. Cell proliferation regulatory pathways have been associated with plaque progression, stenosis, and restenosis after angioplasty and with cancer progression. Alterations in cell adhesion molecules have been linked to plaque formation and thrombosis and to tumor invasion and metastasis. Altered expression of proteases associated with thrombolysis has been implicated in atherosclerotic plaque expansion and hemorrhage and in the invasion and metastasis of malignant neoplasms. Ligand-growth factor receptor interactions have been associated with early atherosclerotic lesions and with cancer development and spread. Nuclear transcription factors have been associated with progression of both diseases. Angiogenesis modulators have been linked to plaque expansion and restenosis of atherosclerotic lesions and to local and metastatic tumor expansion.

Arteriosclerosis↗

PubMed2001

Atherosclerosis and cancer: common molecular pathways of disease development and progression.

Recently, a series of shared molecular pathways have emerged that have in common a significant role in the pathogenesis and progression of both atherosclerosis and cancer. Oxidative stress and the cellular damage that results from it have been implicated in a wide variety of disease processes including atherogenesis and neoplasia. Toxic metabolites produced by cigarette smoking and increased dietary fat intake are implicated in the pathogenesis of both diseases. It has been hypothesized that atherosclerosis may begin when an injury or infection mutates or transforms a single arterial smooth muscle cell in the progenitor of a proliferative clone similar to the most widely held theory of carcinogenesis. Cell proliferation regulatory pathways including genes involved in the GIS checkpoint (p53, pRb, p15, p16, and cyclins A, D, E, and cdk 2,4) have been associated with plaque progression, stenosis and restenosis after angioplasty as well as in cancer progression. Alterations in cell adhesion molecules (integrins, cadherin-catenins) have been linked to plaque formation and thrombosis as well as to tumor invasion and metastasis. Altered expression of proteases associated with thrombolysis has been implicated in atherosclerotic plaque expansion and hemorrhage and in the invasion and metastasis of malignancy. Ligand-growth factor receptor interactions (tyrosine kinases) have been associated with early atherosclerotic lesions as well as cancer development and spread. Nuclear transcription factors such as NFkappaB have been associated with progression of both diseases. Angiogenesis modulators have recently been linked to plaque expansion and restenosis of atherosclerotic lesions as well as local and metastatic tumor expansion. Common disease treatments, such as the use of growth factor inhibitors and radiation treatment, established anticancer treatments, were recently introduced into atherosclerosis therapeutic strategies to prevent restenosis after angioplasty and endarterectomy. In conclusion, a series of molecular pathways of disease development and progression common to atherosclerosis and cancer support that the world's two most common diseases are far more closely aligned than previously believed and that emerging anti-inflammatory and antiproliferative therapeutic strategies may ultimately be efficacious in both conditions.

Arteriosclerosis↗

PubMed1999

The treatment of anxiety disorders in children and adolescents.

Anxiety disorders are the most common psychiatric conditions in the pediatric population, with prevalence estimates ranging from 5-18%. Children and adolescents with excessive anxiety often meet diagnostic criteria for a number of disorders within the DSM-IV. Unfortunately, the current diagnostic system is controversial because of high rates of symptom overlap, comorbidity with other psychiatric disorders, and lack of biological markers that would support a more empirical anxiety nosology. Treatment strategies for pediatric anxiety disorders have important historical roots. Several controlled studies of cognitive-behavioral therapy (CBT) demonstrate efficacy for pediatric anxiety disorders. In contrast, no controlled psychopharmacology studies have demonstrated efficacy in children and adolescents with anxiety disorders, except obsessive-compulsive disorder; however, several large, methodologically sound psychopharmacotherapy trials are underway for pediatric anxiety disorders. This update will review the current status of psychosocial and psychopharmacologic treatment of pediatric anxiety disorders. In addition, a brief discussion of nosology, epidemiology, and developmental course of anxiety is included. Preliminary psychopharmacology treatment and CBT treatment algorithms are presented for pediatric anxiety disorders, based on the best available data. Recommendations for future research directions are also discussed.

Adolescent↗

PubMed1999

Cardiac troponin T and I, echocardiographic [correction of electrocardiographic] wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon.

Cardiac troponin T (cTnT) and troponin I (cTnI) are highly sensitive and specific for detecting myocardial damage even in the presence of skeletal muscle injury. In this study, we assessed whether ultraendurance exercise induced cardiomyocyte injury using plasma cTnT and cTnI measurements, quantitative echocardiographic wall-motion analysis, and ejection fraction measurement in athletes who participated in the Hawaii Ironman Triathlon. Twenty-three athletes (11 men) who completed the triathlon (3.9 km swim, 180.2 km bike, and 42.2 km run) participated in this study. Blood samples were obtained 2 days before and immediately after the triathlon for the determination of cTnT (Enzymun, Roche Diagnostics) and cTnI (Dade Behring) concentrations. Quantitative echocardiographic wall motion analysis and ejection fraction were obtained on 12 of the 23 participants before and immediately after the race. No subject had detectable cTnT or cTnI or abnormal echo score before the race. Following the race, 2 subjects (9%) had marked increases in both cTnT (0.15 and 0.33 microg/L) and cTnI (2.09 and 4.44 microg/L). Four additional subjects (17%) had moderate increases in cTnT (0.04 to 0.05 microg/L) but no detectable cTnI. Race time correlated inversely with cTnT (r = -0.65, p <0.01). Mean change in the number of abnormal echo segments after the race was 6.5 in those with a marked increase in cTnT and cTnI, 2.3 in those with a moderate increase in cTnT, and 1.7 in those with no increase. Ejection fraction decreased by an average of 24% after the race (p <0.002). Thus, ultraendurance exercise may cause myocardial damage as indicated by biochemical cardiac-specific markers and echocardiography. The cellular nature of this damage and whether it is transient or permanent is unclear at present.

Adult↗

PubMed1999

Factor structure of the childhood anxiety sensitivity index.

We developed various factor models of the Childhood Anxiety Sensitivity Index [Silverman, W. K., Fleisig, W., Rabian, B. & Peterson, R. A. (1991). Childhood anxiety sensitivity index. Journal of Clinical Child Psychology, 20, 162-168] and tested the goodness of fit of the models in an independent sample. Of primary interest was to examine the question that characterized the factor analytic studies conducted on the adult version of the anxiety sensitivity index, i.e. the ASI [Reiss, S., Peterson, R. A., Gursky, D. M. & McNally, R. J. (1986). Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behaviour Research and Therapy, 24, 1-8]: is anxiety sensitivity in children a unidimensional construct, an orthogonal multidimensional construct, or a hierarchical construct? Two independent samples (a clinic sample and a nonclinical sample) were used for development and replication of the factor models. The clinic sample consisted of 258 children (105 girls and 153 boys) who presented to a child anxiety disorders specialty clinic. The unselected, nonclinic sample consisted of 249 children (122 girls and 127 boys) enrolled in an elementary school. The results provided strong empirical support for a hierarchical multidimensional model with either three or four first-order factors. The two factors that emerged that appeared to be robust were Physical Concerns and Mental Incapacitation Concerns. What remains unresolved is whether Control of anxiety symptoms and Social Concerns are to be differentiated (as in the hierarchical model with four first-order factors) or not (as in the hierarchical model with three first-order factors). In addition to discussing this issue, the convergence of the present study's findings with past findings obtained with the ASI is discussed.

Anxiety Disorders↗

PubMed1999

Contingency management, self-control, and education support in the treatment of childhood phobic disorders: a randomized clinical trial.

This study evaluated the relative efficacy of an exposure-based contingency management (CM) treatment condition and an exposure-based cognitive self-control (SC) treatment condition relative to an education support (ES) control condition for treating children with phobic disorders. Eighty-one children and their parents completed a 10-week treatment program in which children and parents were seen in separate treatment sessions with the therapist, followed by a brief conjoint meeting. Children in both the CM and SC conditions showed substantial improvement on all of the outcome measures. These gains were maintained at 3-, 6-, and 12-month follow-ups. Interestingly, children in the ES condition also showed comparable improvements at posttreatment and at 3-, 6-, and 12-month follow-ups. Implications of the findings are discussed with respect to knowledge development and clinical practice.

Analysis of Variance↗

PubMed1999

Treating anxiety disorders in children with group cognitive-behaviorial therapy: a randomized clinical trial.

A randomized clinical trial evaluated the therapeutic efficacy of group cognitive-behavioral therapy (GCBT) versus a wait-list control (WLC) condition to treat anxiety disorders in children. Results indicated that GCBT, with concurrent parent sessions, was highly efficacious in producing and maintaining treatment gains. Children in GCBT showed substantial improvement on all the main outcome measures, and these gains were maintained at 3-, 6-, and 12-month follow-ups. Children in the WLC condition did not show improvements from the pre- to the postwait assessment point. These findings are discussed in terms of the need to continue to advance the development of practical, as well as conceptual, knowledge of efficacious treatment for anxiety disorders in children.

Anxiety Disorders↗

PubMed1999

Acute changes in serum lipids and lipoprotein subclasses in triathletes as assessed by proton nuclear magnetic resonance spectroscopy.

Exercise is associated with changes in lipids that may protect against coronary heart disease (CHD). In this study of 28 triathletes, we analyzed acute changes in serum lipid and lipoprotein concentrations after completion of the 1995 World Championship Hawaii Ironman Triathlon. With standard laboratory assays, we demonstrate significant decreases in total cholesterol, VLDL cholesterol, ApoB100, and Lp(a). Total HDL cholesterol increased significantly immediately after the race. With a novel proton NMR spectroscopy assay, we demonstrate that smaller diameter LDL particles, corresponding to small, dense LDL, declined by 62%. Moreover, larger HDL subclasses, whose levels are inversely associated with CHD, increased significantly by 11%. Smaller HDL subclasses, which have been directly associated with CHD in some studies, acutely decreased by 16%. Therefore, exercise not only acutely induces changes in lipoprotein concentrations among the standard species in a manner that favorably affects CHD risk, but also induces favorable changes in specific lipoprotein subclass size distribution that also may alter CHD risk independently of the total lipoprotein serum concentration.

Adult↗

PubMed1999

Characterization of a cholesterol response element (CRE) in the promoter of the cholesteryl ester transfer protein gene: functional role of the transcription factors SREBP-1a, -2, and YY1.

Cholesteryl ester transfer protein (CETP) is expressed in human adipocytes, where it acts to promote selective uptake of HDL-CE (Benoist, F., M. McDonnell, P. Lau, R. Milne, and R. McPherson. 1997. J. Biol. Chem. 272: 23572;-23577). In contrast to other major sterol-responsive genes such as 3-hydroxy-3-methylglutaryl coenzyme A reductase CETP expression is up-regulated rather than down-regulated in response to cholesterol. To define elements involved in cholesterol-mediated up-regulation of CETP gene expression, deletion derivatives of the CETP promoter were cloned into a luciferase reporter construct and transfected into the human liposarcoma cell line SW872, cultured in the presence or absence of lipoproteins. A fragment associated with a positive cholesterol response was identified between nucleotides -361 and -138 (relative to the initiation site of transcription) of the promoter. This region contains a tandem repeat of a sequence known to mediate sterol dependent regulation of the hamster HMG-CoA reductase gene. We have putatively denoted this region, the cholesterol response element (CRE). Using gel mobility shift assays we demonstrate that both YY1 and SREBP-1 interact with the CRE of CETP. Furthermore, in transient co-transfection experiments, both YY1 and SREBP-1a were found to trans-activate, in a dose-dependent manner, the luciferase activity of constructs harboring the CRE. We also demonstrate that SREBP-2, is able to trans-activate a luciferase construct harboring the CRE although much less effectively as compared to SREBP-1. Finally, functional analysis of the CRE confirms its regulatory role in modulating CETP gene expression through its interaction with YY1 and SREBP-1a.

Animals↗

PubMed1998

Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome.

Long QT syndrome (LQTS), is an inherited cardiac disorder in which ventricular tachyarrhythmias predispose affected individuals to syncope, seizures, and sudden death. Characteristic electrocardiographic findings include a prolonged QT interval, T wave alternans, and notched T waves. We have screened LQTS patients from 89 families for mutations in the pore region of HERG , the K+ channel gene previously associated with chromosome 7-linked LQT2. In six unrelated LQTS kindreds, single-strand conformation polymorphism analyses identified aberrant conformers in all affected family members. These conformers were not seen in over 100 unaffected, unrelated control individuals, suggesting that they represent pathogenic LQTS mutations. DNA sequence analyses of the aberrant conformers demonstrated that they reflect five different missense mutations: V612L, A614V, N629D, N629S, and N633S. The missense mutation A614V was found in two unrelated families. Further functional studies will be required to determine what effect each of these changes may have on HERG channel function.

Adult↗

PubMed1998

Social anxiety in children with anxiety disorders: relation with social and emotional functioning.

Investigated the psychometric properties of the Social Anxiety Scale for children-Revised (SASC-R) as well as relations between social anxiety and children's social and emotional functioning. Participants were a clinic sample of children, ages 6-11 with anxiety disorders (N = 154) who completed the SASC-R. For a subset of these children, parent ratings of social skills, and self-ratings of perceived competence and peer interactions were also obtained. Factor analysis of the SASC-R supported the original three-factor solution and internal consistencies were in the acceptable range. Among children with simple phobia, scores on the SASC-R differentiated those with and without a comorbid social-based anxiety disorder. Social anxiety was also associated with impairments in social and emotional functioning. Specifically, highly socially anxious children reported low levels of social acceptance and global self-esteem and more negative peer interactions. Girls with high levels of social anxiety were also rated by parents as having poor social skills, particularly in the areas of assertive and responsible social behavior.

Anxiety Disorders↗

PubMed1998

Testing the utility of the anxiety sensitivity construct in children and adolescents referred for anxiety disorders.

Tested the utility of assessing anxiety sensitivity in children by investigating the incremental validity of the Childhood Anxiety Sensitivity Index (CASI) in a sample of clinic-referred children and adolescents ages 6 to 17 (N = 280). In the first test we examined whether the CASI would predict variance in trait anxiety beyond that predicted by measures of manifest anxiety and fear in children ages 6 to 11 (n = 202) and adolescents ages 12 to 17 (n = 78). In the next test, we examined whether the CASI would predict variance in fear beyond that predicted by a measure of trait anxiety for both age groups. In addition, age was tested as a continuous moderator of the CASI's incremental validity. No evidence was found to suggest that age systematically influences the CASI's incremental validity in the age ranges for which the CASI was designed. We discuss the results in terms of the utility of the CASI with younger and older age groups of children and the importance of such a measure for investigating the development of anxiety disorders in children.

Adolescent↗

PubMed1997

Evaluation and clinical application of a direct low-density lipoprotein cholesterol assay in normolipidemic and hyperlipidemic adults.

This study examines the performance and clinical use of a commercial immunoseparation assay for low-density lipoprotein (LDL) cholesterol in a sample population of normolipidemic and hyperlipidemic adult volunteers. Using paired fasting and nonfasting samples, we compared the direct LDL assay with the beta quantification method and the Friedewald calculation. Overall, the direct LDL assay correctly classified 82% and 60% of fasting and nonfasting subjects, respectively, into National Cholesterol Education Program risk groups. The Friedewald method correctly classified 84% of subjects. The fasting direct LDL assay has comparable positive and negative predictive values to the Friedewald method, except at an LDL cholesterol of 100 mg/dl. The nonfasting direct LDL assay demonstrates unacceptable positive predictive values when LDL cholesterol decreases to the 130 to 159 and > or = 160 mg/dl categories. Overall, direct LDL assay demonstrates limitations in the nonfasting state and at the LDL cholesterol level of 100 mg/dl used for patients with established coronary heart disease.

Adult↗

PubMed1997

Left ventricular hypertrophy in athletes.

Left ventricular wall thickness >1.3 cm, septal-to-posterior wall ratios > 1.5, diastolic left ventricular size >6.0 cm, and eccentric or concentric remodeling are rare in athletes. Values outside of these cutoffs in an athlete of any age probably represent a pathologic state.

Adult↗

PubMed1997

Intestinal transcription and synthesis of apolipoprotein AI is regulated by five natural polymorphisms upstream of the apolipoprotein CIII gene.

To understand the factors contributing to the synthesis of human apolipoprotein AI (apoAI), relative apoAI synthesis was measured from endoscopic biopsy samples obtained from 18 healthy volunteers. The relative amount of apoAI synthesis was directly correlated with steady state intestinal apoAI mRNA levels and a 10-fold within-group variability was observed. Analysis of genomic DNA from the subjects revealed five polymorphic sites which defined two haplotypes in the intestinal enhancer region of the apoAI gene located upstream of the apolipoprotein CIII gene transcriptional start site (+ 1): (-641 C to A, -630 G to A, -625 T to deletion, -482 C to T, and -455 T to C). The population frequencies of the wild-type and mutant alleles were 0.53 and 0.44, respectively. Mean steady state apoAI mRNA levels and mean relative apoAI synthesis were 49 and 37% lower, respectively, in homozygotes for the mutant allele and 28 and 41% lower, respectively, in heterozygotes than in homozygotes for the wild-type allele (P < 0.05 for both). Site-directed mutants of apoAI gene promoter/reporter constructs containing the above mutations were transfected into Caco-2 cells and showed a 46% decrease in transcriptional activity compared with the wild type (P < 0.001); however, no significant differences were observed in HepG2 cells. Electrophoretic mobility shift assays showed that the mutated sequences from -655 to -610 bound Caco-2 cell nuclear protein(s) while the wild type did not. These results indicate that intestinal apoAI gene transcription and protein synthesis are genetically determined and are reduced in the presence of common mutations which induced binding of nuclear protein(s), possibly a transcriptional repressor.

Adult↗