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Biomedical subjects

J Levy

Publications and source records attributed to J Levy.

At least 19 recordsLinked to original sources
PubMed2001

Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells.

The biochemical mechanisms underlying the inhibitory effects of lycopene, the main tomato carotenoid, on the growth of cancer cells are largely unknown. It has been hypothesized that lycopene derivatives may act as ligands for a nuclear receptor in analogy to retinoic acid, the hormone derived from beta-carotene. The inhibition of human mammary cancer (MCF-7) cell growth and the transactivation of the retinoic acid receptor (RAR) reporter gene by synthetic acyclo-retinoic acid, the open chain analog of retinoic acid, was compared to the effects of lycopene and retinoic acid in the same systems. Acyclo-retinoic acid activated the DR-5 retinoic acid response element with a approximately 100-fold lower potency than retinoic acid. This effect was independent of cotransfection with the RARalpha receptor. Lycopene exhibited only very modest activity in this system. In contrast to the results from the transactivation studies, acyclo-retinoic acid, retinoic acid, and lycopene inhibited cell growth with a similar potency. Preincubation with each of the three compounds slowed down cell cycle progression from G1 to S phase. In summary, acyclo-retinoic acid inhibited cancer cell growth and interacted with RAR. However, it exhibited low affinity for RAR and a correspondingly low efficacy in activating this receptor, indicating that RAR does not mediate the growth inhibitory effect of the compound. In addition, the concentrations of acyclo-retinoic acid and of lycopene required for inducing inhibition of cell growth were similar, suggesting that acyclo-retinoic acid is unlikely to be the active metabolite of lycopene.

Antineoplastic Agents↗
PubMed2001

Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-cdk2 complexes.

Numerous studies have demonstrated the anticancer activity of the tomato carotenoid, lycopene. However, the molecular mechanism of this action remains unknown. Lycopene inhibition of human breast and endometrial cancer cell growth is associated with inhibition of cell cycle progression at the G(1) phase. In this study we determined the lycopene-mediated changes in the cell cycle machinery. Cells synchronized in the G(1) phase by serum deprivation were treated with lycopene or vehicle and restimulated with 5% serum. Lycopene treatment decreased serum-induced phosphorylation of the retinoblastoma protein and related pocket proteins. This effect was associated with reduced cyclin-dependent kinase (cdk4 and cdk2) activities with no alterations in CDK protein levels. Lycopene caused a decrease in cyclin D1 and D3 levels whereas cyclin E levels did not change. The CDK inhibitor p21(Cip1/Waf1) abundance was reduced while p27(Kip1) levels were unaltered in comparison to control cells. Serum stimulation of control cells resulted in reduction in the p27 content in the cyclin E--cdk2 complex and its accumulation in the cyclin D1--cdk4 complex. This change in distribution was largely prevented by lycopene treatment. These results suggest that lycopene inhibits cell cycle progression via reduction of the cyclin D level and retention of p27 in cyclin E--cdk2, thus leading to inhibition of G(1) CDK activities.

Adenocarcinoma↗
PubMed2001

Oral poliomyelitis vaccine: time to change?

For 3 decades, vaccination against poliomyelitis has rested mainly on the use of the oral attenuated vaccine (OPV). In countries where wild type poliomyelitis has been successfully controlled by OPV, the rare cases of poliomyelitis that can still be identified occur in vaccinees or their contacts and are caused by vaccine related strains. Over years, data indicating that the inactivated vaccine (IPV) also has the potential to control poliomyelitis and that there are no known risks associated with the use of this vaccine have accumulated. The reasons for changes in vaccine policy in industrialised countries and the situation of the global effort of poliomyelitis immunisation are described. Some of the issues and challenges for the future are reviewed.

Health Policy↗
PubMed2001

Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility.

The signaling events downstream of integrins that regulate cell attachment and motility are only partially understood. Using osteoclasts and transfected 293 cells, we find that a molecular complex comprising Src, Pyk2, and Cbl functions to regulate cell adhesion and motility. The activation of integrin alpha(v)beta(3) induces the [Ca(2+)](i)-dependent phosphorylation of Pyk2 Y402, its association with Src SH2, Src activation, and the Src SH3-dependent recruitment and phosphorylation of c-Cbl. Furthermore, the PTB domain of Cbl is shown to bind to phosphorylated Tyr-416 in the activation loop of Src, the autophosphorylation site of Src, inhibiting Src kinase activity and integrin-mediated adhesion. Finally, we show that deletion of c Src or c-Cbl leads to a decrease in osteoclast migration. Thus, binding of alpha(v)beta(3) integrin induces the formation of a Pyk2/Src/Cbl complex in which Cbl is a key regulator of Src kinase activity and of cell adhesion and migration. These findings may explain the osteopetrotic phenotype in the Src(-/-) mice.

CSK Tyrosine-Protein Kinase↗
PubMed2001

Tangled1: a microtubule binding protein required for the spatial control of cytokinesis in maize.

Spatial control of cytokinesis in plant cells depends on guidance of the cytokinetic apparatus, the phragmoplast, to a cortical "division site" established before mitosis. Previously, we showed that the Tangled1 (Tan1) gene of maize is required for this process during maize leaf development (Cleary, A.L., and L.G. Smith. 1998. Plant Cell. 10:1875-1888.). Here, we show that the Tan1 gene is expressed in dividing cells and encodes a highly basic protein that can directly bind to microtubules (MTs). Moreover, proteins recognized by anti-TAN1 antibodies are preferentially associated with the MT-containing cytoskeletal structures that are misoriented in dividing cells of tan1 mutants. These results suggest that TAN1 protein participates in the orientation of cytoskeletal structures in dividing cells through an association with MTs.

Cell Division↗
PubMed2001

Availability and quality of industry and occupation information in the Massachusetts Cancer Registry.

BACKGROUND: Industry and occupation (I/O) data from state cancer registries can be useful in generating and evaluating hypotheses about occupational cancer risks. The quality of these data is uncertain. METHODS: We reviewed medical records on 1,020 cases from the Massachusetts Cancer Registry (MCR). We compared the presence and detail of I/O data from this dedicated record review (DRR) with routine reporting to the MCR in order to evaluate the potential to increase the availability of I/O data. RESULTS: Compared to routine reporting, the DRR increased the percentage of codable I/O data from 63.6 to 80.4%. The DRR also provided more detail in existing codes in 15.4% of cases. Other sections of the medical record in addition to the face sheet and sections of the record from the period before cancer diagnosis were important sources of additional information. Duration and timing of the corresponding I/O information were rarely recorded. CONCLUSIONS: The nearly one-third (32%) of records that had some improvement in I/O information with a dedicated review indicates considerable opportunity to improve the utility of this resource.

Adolescent↗
PubMed2001

Attitude of Belgian pediatricians toward strategy in acute pyelonephritis.

To investigate the attitude of Belgian pediatricians toward the management and treatment of children with suspected acute pyelonephritis, a short letter was sent to all Belgian pediatricians (1,200). It contained a brief description of a clinical case strongly suggestive of acute pyelonephritis followed by a series of questions centered on complementary examinations to be performed, need of hospitalization and treatment. A total of 583 responses were received (49%). In the acute phase, 99% of pediatricians perform urine cultures, 87% blood examinations, and 76% renal ultrasound. Dimercaptosuccinate (DMSA) scintigraphy is performed during the acute phase by 37% and during follow-up by 32% of all pediatricians. A voiding cystogram is requested by 71%. Ambulatory treatment is considered by 30% of responders. Amoxicillin/clavulanic acid (44%) and trimethoprim/sulfonamide (22%) are the most frequently used oral antibiotics. Private pediatricians perform fewer examinations and more frequently consider ambulatory treatment of acute pyelonephritis, compared to pediatricians working in hospitals. Among Belgian pediatricians, attitudes toward the diagnosis and treatment of acute pyelonephritis are heterogeneous. This survey underlines the need for properly documented prospective studies for the evaluation of different treatment modalities in childhood acute pyelonephritis.

Acute Disease↗
PubMed2001

Treatment of children with acute pyelonephritis: a prospective randomized study.

The aim of this study was to compare, in children with acute pyelonephritis, the efficacy of 7 days' (group A) and 3 days' (group B) intravenous antibiotics, both followed by an oral treatment. Children were randomized after 3 days of intravenous treatment. Technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy was performed within the first days after admission and repeated 6 months later. Total or partial persistence of renal abnormalities on the 6-month DMSA scintigraphy was used as the endpoint of the study. Among the 92 children included in the study, 87 were followed for at least 6 months (43 in group A and 44 in group B) and were eligible for analysis. Late DMSA was abnormal in 9 kidneys of group A and 12 kidneys of group B, representing respectively 24% and 44% of kidneys with abnormalities on the initial DMSA (difference statistically not significant). When the patients were stratified according to the delay of treatment, the percentage of patients with sequelae in group A was comparable, whether the delay was less or more than 1 week. In group B, the percentage of patients with sequelae was significantly higher (P<0.01) when the delay was more than 1 week.

Acute Disease↗
PubMed2001

Neurophysiologic studies in congenital insensitivity to pain with anhidrosis.

Thirteen patients with congenital insensitivity to pain and anhidrosis, carrying a mutation at the TRK-A gene, were studied. Neurologic examination revealed vestigial pain sensitivity, suggesting an incomplete involvement of the affected nerves. All 13 patients manifested normal electrophysiologic studies but striking absence of sympathetic skin responses. We suggest the use of the sympathetic skin response test in the clinical evaluation of patients suspected of having congenital insensitivity to pain and anhidrosis.

Child↗
PubMed2001

Fetal serum levels of insulin, growth hormone and insulin-like growth factor-I in concordant and discordant twin gestations.

OBJECTIVE: To examine the role of insulin, growth hormone and insulin-like growth factor (IGF)-I in concordant and discordant twin pairs. METHODS: Umbilical cord serum samples were obtained from 20 twin pairs with weight discordancy (intertwin birth weight difference > 20%) and from 20 concordant twins (intertwin birth weight difference < 20%), both groups of similar gestational age, gravidity, and parity. The serum samples were analyzed for the levels of IGF-I, growth hormone and insulin in both maternal and fetal compartments. RESULTS: Among the group of discordant twins, the normally grown twin, in all cases, had significantly higher cord serum IGF-I levels than their growth-restricted co-twin (108 +/- 73 ng/ml vs. 39 +/- 24 ng/ml; p < 0.01). There were no significant intertwin differences in the cord blood IGF-I levels in the concordant twin pairs (87 +/- 44 vs. 88 +/- 48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with intertwin birth weight differences. CONCLUSION: These data demonstrate that IGF-I is important in the regulation of both normal and restricted fetal growth in utero, and its action appears to be, at least in part, through an endocrine action. The precise role of growth hormone and insulin in fetal growth restriction remains uncertain.

Female↗
PubMed2001

Does cisapride influence cardiac rhythm? Results of a United States multicenter, double-blind, placebo-controlled pediatric study.

BACKGROUND: Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program. Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use. METHODS: Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment. RESULTS: Mean QTc among patients taking the drug was 408+/-18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2+/-20 ms. CONCLUSIONS: In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.

Arrhythmias, Cardiac↗
PubMed2001

Electrogastrographic norms in children: toward the development of standard methods, reproducible results, and reliable normative data.

BACKGROUND: Surface electrogastrography (EGG) is a noninvasive technique that detects gastric myoelectrical electric activity, principally the underlying pacemaker activity generated by the specialized interstitial cells of Cajal. Interest in the use of this methodology has grown because of its potential applications in describing functional gastrointestinal disorders, particularly as a tool in the evaluation of nausea, anorexia, and other dyspeptic symptoms. METHODS: Fifty-five healthy volunteers (27 female), ranging in age from 6 to 18 years (mean, 11.7 years), were studied for a 1-hour baseline preprandial period and a 1-hour postprandial period after consumption of a standard 448-kcal meal. Recordings were obtained with an EGG Digitrapper or modified Polygraph (Medtronic-Synectics, Shoreview, MN). Spectral analysis by an autoregressive moving average method was used to extract numerical data on the power and frequency of gastric electrical activity from the EGG signal. RESULTS: The authors present normative data for healthy children and adolescents studied under a standardized protocol. Mean dominant frequency was found to be 2.9 +/- 0.40 cycles per minute preprandially and 3.1 +/- 0.35 postprandially, with 80% +/- 13% of test time spent in the normogastric range (2-4 cycles per minute) before and 85% +/- 11% after the test meal. The response of several key parameters to meal consumption was considered, and the effects of age, gender, and body mass index (BMI) on the EGG were sought. CONCLUSIONS: There is a postprandial increase in the rhythmicity and amplitude of gastric slow waves, as other investigators have shown in adults. Key normative values are not dependent on age, gender, or BMI. The authors discuss limitations in the data set and its interpretability. The authors establish a normative data set after developing a standardized recording protocol and test meal and show that EGG recordings can be obtained reliably in the pediatric population. Development of similar norms by investigators using the EGG is crucial for future exploration of the validity and clinical application of the EGG. Differences in test conditions of signal detection and analytic methods influence EGG results substantially, and caution should be used when comparing results across centers.

Adolescent↗
PubMed2001

Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life.

OBJECTIVE: To describe patterns of clinical and immunologic progression in children who are vertically infected with the human immunodeficiency virus. METHODS: Children who were born to mothers who were infected with the human immunodeficiency virus in 11 European centers were enrolled at birth in a prospective study and followed according to a standard protocol. At each visit, a clinical and immunologic class was allocated according to guidelines of the Centers for Disease Control and Prevention (CDC). Progression to serious disease and death was assessed, allowing for available and actual antiretroviral therapy (ART). CDC class at each visit was assessed cross-sectionally. RESULTS: More than 15% of infected children will have progressed to category C or death by age 1 year and nearly 50% by 10 years. Just under 20% of children will have evidence of severe immunodeficiency by age 1 and 75% by 10 years. In general, immune status poorly reflected clinical condition. Children who were born after 1994, when the recommendation of earlier initiation of more active therapy was introduced, were significantly less likely to progress than those who were born when treatment was not widely available or was largely confined to zidovudine monotherapy. Estimated progression to CDC class C or death initially was faster in untreated than in treated children, but by 10 years estimated cumulative progression was similar in both groups. Treatment started before class C disease was associated with significantly slower progression. Cross-sectional analysis showed that children largely are symptom-free throughout their lives. After 4 years of age, fewer than 25% of infected children had symptoms at any one time, irrespective of ART received. CONCLUSION: Vertically infected children are without serious symptoms or signs for most of the time. The prognosis has improved with more widespread availability and use of combination ART. These findings have implications for health, education, and other support-service provision.

Age Distribution↗
PubMed2001

Video vs. CD-ROM for teaching pelvic anatomy to third-year medical students. A comparison.

OBJECTIVE: To compare the effectiveness and student acceptance of video and CD-ROM review of pelvic anatomy in third-year obstetrics and gynecology students. STUDY DESIGN: A 34-item pretest was administered on the first day of the clerkship. Students were then randomized to watch a 45-minute video or use an interactive CD-ROM at home. All students took a posttest identical to the pretest. Examination scores were compared by paired and unpaired t test. Students completed a questionnaire on each method's ease, appropriateness, organization, appeal and time spent and whether they would recommend the method to others. RESULTS: One hundred seventy-six students were randomized, 88 to CD and 88 to video. There was 100% compliance, although not all questionnaire items were completed. The mean pretest score for both groups was 50%. The posttest CD mean score was significantly different from the posttest video mean (64% vs. 70%). Both groups significantly improved after the intervention. The video group noted ease of use, but only 49% recommended it for the future. The CD-ROM was recommended by 80%. Student comments favored the CD-ROM. CONCLUSION: Use of video review resulted in short-term significantly higher test scores, but students preferred an interactive CD-ROM. This method should be made available to all students during the rotation.

CD-I↗
PubMed2001

Is dual-task slowing instruction dependent?

When 2 tasks must be performed concurrently, each requiring a choice of response, dual-task slowing is typically found. However, E. H. Schumacher et al. (1997) reported that dual-task slowing can be eliminated when equal priority is assigned to each task. Experiment 1 largely confirmed this with the same tasks as Schumacher et al. (tasks using stimulus-response combinations of visual-manual and auditory-vocal pairings). Experiment 2 retained the equal-priority instructions but switched the task pairings (to visual-vocal and auditory-manual); substantial dual-task slowing occurred. Experiment 3 used the same two response sets but only a single stimulus; slowing was again obtained despite equal priority instructions. Equalizing task priority was not sufficient to eliminate interference; relatively unusual cases in which dual-task interference is eliminated seem to depend on task-specific features.

Choice Behavior↗