Search PubMed⌕ Search

Biomedical subjects

D Levy

Publications and source records attributed to D Levy.

At least 55 records · Page 3Linked to original sources
PubMed2001

A case-control study of microsomal epoxide hydrolase, smoking, meat consumption, glutathione S-transferase M3, and risk of colorectal adenomas.

We estimated associations between polymorphisms in the gene encoding microsomal epoxide hydrolase (mEH) among 464 cases diagnosed with first occurrence of colorectal adenoma and 510 matched controls. In an analysis controlling only for the matching variables, we found little or no association between adenoma and mEH genotypes defined by polymorphisms at either codon 113 and 139 or mEH activity predicted by both polymorphisms. However, in subsequent analyses, high predicted mEH activity was significantly associated with adenoma among certain subgroups defined by smoking history [odds ratio (OR), 4.27; 95% confidence interval (CI), 1.68-10.81 among current smokers; interaction, P = 0.11], meat consumption (OR, 2.47; CI, 0.99-6.19 among individuals who regularly eat well-done meat; interaction, P = 0.03), and genotypes for the *A/*B polymorphism in the gene encoding glutatione S-transferase M3 (OR, 2.60; CI, 1.28-5.28 among individuals with *A*A genotype; interaction, P = 0.03). These findings are consistent with causal roles for environmental polycyclic aromatic hydrocarbons and genetically encoded variants in enzymes whose actions lead to the production of activated polycyclic aromatic hydrocarbon metabolites.

Adenoma↗
PubMed2001

Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study.

BACKGROUND: We examined the relative importance of diastolic (DBP), systolic (SBP) and pulse pressure (PP) as predictors of coronary heart disease (CHD) risk in different age groups of Framingham Heart Study participants. METHODS AND RESULTS: We studied 3060 men and 3479 women between 20 and 79 years of age who were free of CHD and were not on antihypertensive drug therapy at baseline. Cox regression adjusted for age, sex, and other risk factors was used to assess the relations of BP indexes to CHD risk over a 20-year follow-up. In the group <50 years of age, DBP was the strongest predictor of CHD risk (hazard ratio [HR] per 10 mm Hg increment, 1.34; 95% CI, 1.18 to 1.51) rather than SBP (HR, 1.14; 95% CI, 1.06 to 1.24) or PP (HR, 1.02; 95% CI, 0.89 to 1.17). In the group 50 to 59 years of age, risks were comparable for all 3 BP indexes. In the older age group, the strongest predictor of CHD risk was PP (HR, 1.24; 95% CI, 1.16 to 1.33). When both SBP and DBP were considered jointly, the former was directly and the latter was inversely related to CHD risk in the oldest age group CONCLUSIONS: With increasing age, there was a gradual shift from DBP to SBP and then to PP as predictors of CHD risk. In patients <50 years of age, DBP was the strongest predictor. Age 50 to 59 years was a transition period when all 3 BP indexes were comparable predictors, and from 60 years of age on, DBP was negatively related to CHD risk so that PP became superior to SBP.

Adult↗
PubMed2001

Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study.

BACKGROUND: Apolipoprotein (apo) E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. The apo E4 (Arg112-Cys) polymorphism has been associated with dementia and hypercholesterolemia. We investigated the relation of APOE genotype to cardiovascular disease (CVD) in the Framingham Offspring Study. METHODS AND RESULTS: DNA was isolated from 3413 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, 20.7% had apo E4/4 or E3/4 (Group E4); 14.1% had apo E2/2 or E2/3 (Group E2) and 63.9% had the apo E3/3 genotype (Group E3). Subjects with E2/4 (1.3%) were excluded. Period prevalence of CVD between examinations 1 and 5 (1971-1994) (366 events) was related to APOE genotype. Age adjusted period prevalence of CVD in men was 18.6% for Group E4, 18.2% for Group E2 and 12.7% for Group E3 (P=0.004); while in women these rates were 9.9, 4.9, and 6.6%, respectively (P=0.037). After adjustment for non-lipid risk factors the relative odds for CVD in Group E2 men was 1.79 (P=0.0098) and in Group E4 it was 1.63 (P=0.0086) compared with the Group E3; while in Group E4 women it was 1.56 (P=0.054). After adjustment for all CVD risk factors, the relative odds in Group E2 men was 1.94 (P=0.004) and in Group E4 men it was 1.51 (P=0.0262). CONCLUSIONS: The presence of the apo E2 or apo E4 alleles in men is associated with significantly greater CVD risk. This genotypic information may help to identify individuals at increased risk for CVD events.

Adolescent↗
PubMed2001

Hemostatic state and atrial fibrillation (the Framingham Offspring Study).

Atrial fibrillation (AF) is strongly associated with thromboembolic complications, although the mechanism for the increased risk has not been fully explained. To determine whether AF might be associated with a hypercoagulable state, we studied hemostatic factors in subjects with or without AF in the Framingham Heart Study. In 3,577 subjects, we measured fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor-1 antigen. Forty-seven subjects had AF at the index clinic examination and 15 had AF on a prior examination, but not on the current examination. Before matching, the 47 subjects with prevalent AF had higher levels of fibrinogen, von Willebrand factor, and tPA antigen than those without AF, all p < or =0.03. Compared with 167 referent subjects matched for age, sex, and other risk factors, those with AF had higher tPA antigen levels than those without AF, 1 1.8 +/- 4.0 ng/ml versus 10.5 +/- 3.9 ng/ml (p = 0.04). However, when further stratified according to their cardiovascular disease status, the differences in hemostatic factors were no longer significant. We conclude that the prothrombotic profile associated with AF was explained by the risk factors of the subjects and the presence of cardiovascular disease. Nonetheless, the hemostatic changes may contribute toward the propensity for thromboembolic complications in AF. Further prospective studies are needed to evaluate whether measurement of these and other hemostatic factors will identify patients with AF who are at increased risk for thromboembolic complications, and who may therefore benefit from more intensive therapy.

Aged↗
PubMed2001

Bone mass and the risk of colon cancer among postmenopausal women: the Framingham study.

Although postmenopausal estrogen use has been associated with a lower risk of colon cancer in women, some studies do not confirm such findings. No known study has examined the effect of cumulative estrogen exposure on colon cancer risk. Bone mass has been proposed as a marker of cumulative exposure to endogenous and exogenous estrogens. By using data on 1,394 Massachusetts women in the Framingham Study who underwent hand radiography in 1967-1970, the authors examined the association between bone mass (from relative areas of the second metacarpal) and colon cancer incidence. Over 27 years of follow-up, 44 incident colon cancer cases occurred. Colon cancer incidence decreased from 2.19 per 1,000 person-years among the women in the lowest age-specific tertile of bone mass to 1.59 and 1.08 among women in the middle and the highest tertiles, respectively. After adjustment for age and other potential confounding factors, the rate ratios of colon cancer were 1.0, 0.7 (95% confidence interval: 0.3, 1.3), and 0.4 (95% confidence interval: 0.2, 0.9) from the lowest to the highest tertile (p for trend = 0.033). No association was found between bone mass and rectal cancer. The findings suggest that women with higher bone mass, perhaps reflecting greater cumulative estrogen exposure, have a decreased risk of colon cancer.

Adult↗
PubMed2001

A rapid and efficient two-step gel electrophoresis method for the purification of major rye grass pollen allergens.

Purified proteins are mandatory for molecular, immunological and cellular studies. However, purification of proteins from complex mixtures requires specialised chromatography methods (i.e., gel filtration, ion exchange, etc.) using fast protein liquid chromatography (FPLC) or high-performance liquid chromatography (HPLC) systems. Such systems are expensive and certain proteins require two or more different steps for sufficient purity and generally result in low recovery. The aim of this study was to develop a rapid, inexpensive and efficient gel-electrophoresis-based protein purification method using basic and readily available laboratory equipment. We have used crude rye grass pollen extract to purify the major allergens Lol p 1 and Lol p 5 as the model protein candidates. Total proteins were resolved on large primary gel and Coomassie Brilliant Blue (CBB)-stained Lol p 1/5 allergens were excised and purified on a secondary "mini"-gel. Purified proteins were extracted from unstained separating gels and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analyses. Silver-stained SDS-PAGE gels resolved pure proteins (i.e., 875 microg of Lol p 1 recovered from a 8 mg crude starting material) while immunoblot analysis confirmed immunological reactivity of the purified proteins. Such a purification method is rapid, inexpensive, and efficient in generating proteins of sufficient purity for use in monoclonal antibody (mAb) production, protein sequencing and general molecular, immunological, and cellular studies.

Allergens↗
PubMed2001

Trichostatin A inhibits beta-casein expression in mammary epithelial cells.

Many aspects of cellular behavior are defined by the content of information provided by association of the extracellular matrix (ECM) and with cell membrane receptors. When cultured in the presence of laminin-containing ECM and prolactin (Prl), normal mammary epithelial cells express the milk protein beta-casein. We have previously found that the minimal ECM- and Prl-responsive enhancer element BCE-1 was only active when stably integrated into chromatin, and that trichostatin A (TSA), a reagent that leads to alterations in chromatin structure, was able to activate the integrated enhancer element. We now show that endogenous beta-casein gene, which is controlled by a genetic assembly that is highly similar to that of BCE-1 and which is also activated by incubation in ECM and Prl, is instead inhibited by TSA. We provide evidence that the differing response of beta-casein and BCE-1 to TSA is neither due to an unusual effect of TSA on mammary epithelial cells, nor to secondary consequences from the expression of a separate gene, nor to a particular property of the BCE-1 construct. As a component of this investigation, we also showed that ECM mediated rapid histone deacetylation in mammary epithelial cells. These results are discussed in combination with previous work showing that TSA mediates the differentiation of many types of cancer cells but inhibits differentiation of some nonmalignant cell types.

Acetylation↗
PubMed2001

The validity of different definitions of radiographic worsening for longitudinal studies of knee osteoarthritis.

Several definitions have been used to characterize radiographic worsening of knee osteoarthritis in longitudinal studies, yet a valid definition with maximal power to detect differences between groups is not known. We used serial radiographs from the Framingham Osteoarthritis Study to compare five dichotomous definitions according to construct validity (strength of association) and discriminant power (power to reject null hypotheses of no difference) for 1) known risk factors for knee osteoarthritis, and 2) development of new knee pain. For risk factors: definitions that included scores for osteophytes (bone spurs) showed good construct validity and discriminant power; a definition using the Kellgren and Lawrence grade of overall knee osteoarthritis was conservative with good construct validity but low discriminant power; a definition based solely on ordinal assessment of joint space narrowing had weak construct validity and low discriminant power. All definitions had comparably strong associations with the development of new knee pain. Similar associations with new knee pain were found when the analysis was confined to either knees with no osteoarthritis at baseline or knees with prevalent osteoarthritis, with increased standard errors for prevalent osteoarthritis. Use of any of these definitions, other than joint space narrowing alone, would permit detection of associations with most known risk factors. Definitions incorporating both osteophytes and joint space narrowing offer the most precise estimation of the association of risk factors with disease worsening.

Aged↗
PubMed2001

Clinical features of panic attacks in schizophrenia.

Since reports have underscored that panic attacks (PA) may be an identifiable state occurring in schizophrenia, we studied the symptomatology of PA in a group of schizophrenic patients. Of 40 patients (21 males and 19 females) attending a clinic for maintenance therapy of schizophrenia, 19 (36.8%) had a lifetime history of PA. Seven among those 19 patients (36.8%) had or had had spontaneous panic attacks, not related to phobic fears or delusional fears, and for the 12 remaining patients, the PA were related to paranoid ideas. Moreover, the paranoid subtype of schizophrenia tends to be more often associated with a history of panic attack than other subtypes of schizophrenia (52.6% vs 23.8%; chi2 = 3.5, P =.06). It seems that there are at least two types of PA in schizophrenic patients. The first one could be independent from the psychotic feature, with no psychopathological link. The second kind of PA could be directly related to a schizophrenic disorder, and found in patients with the paranoid subtype.

Adult↗
PubMed2001

Cooperation between STAT3 and c-jun suppresses Fas transcription.

Decreased Fas expression during tumor progression often results in a loss of Fas-ligand (FasL)-mediated apoptosis. Human and mouse melanoma exhibit an inverse correlation between the degree of Fas cell surface expression, tumorigenicity, and metastatic capacity. The expression of dominant negative Stat3 or c-Jun in melanoma cells efficiently increased Fas expression and sensitized cells to FasL-induced apoptosis. Stat3+/- as well as c-Jun-/- cells exhibited increased Fas cell surface expression and higher sensitivity to FasL-mediated apoptosis. Suppression of Fas expression by Stat3 and c-Jun is uncoupled from Stat3-mediated transcriptional activation. Our findings indicate that Stat3 oncogenic activities could also be mediated through its cooperation with c-Jun, resulting in downregulation of Fas surface expression, which is implicated in the tumor's ability to resist therapy and metastasize.

Animals↗
PubMed2001

Autologous endometrial coculture in patients with in vitro-fertilization (IVF) failure: correlations of outcome with leukemia inhibiting factor (LIF) production.

PROBLEM: To determine if LIF produced by autologous endometrial co-culture (ECC) was associated with outcome in 46 patients with a history of multiple IVF failures. METHOD OF STUDY: The conditioned media (CM) from ECC cells exposed or non-exposed to human embryos was analyzed for LIF. RESULTS: Exposure or non-exposure to an embryo did not result in differing levels of LIF in the CM. LIF levels were significantly greater in the CM than in the serum controls (LIF was not found in the serum controls). Embryos grown on ECC demonstrated a significant improvement in number of blastomeres and fragmentation when compared to embryos grown in conventional media without ECC (6.7 +/- 1.3 vs. 5.6 +/- 1.2 blastomeres and 17.6% +/- 9.3 vs. 26.4% +/- 9.8 fragmentation; P < 0.05). When LIF levels were detectable in the CM, the embryos grown in ECC were of improved quality as compared to the embryos grown only in conventional media and demonstrated a non-significant increase in pregnancy rates (60 vs. 48%, P = 0.50). CONCLUSIONS: We have demonstrated a significant improvement in embryo quality with ECC. The cells in the ECC express LIF. The presence of LIF in the CM was associated with embryonic development and clinical pregnancy.

Adult↗
PubMed2001

Scan reproducibility of magnetic resonance imaging assessment of aortic atherosclerosis burden.

Subclinical atherosclerosis precedes the onset of clinical disease by many years. Noninvasive magnetic resonance imaging (MRI) offers the opportunity to visualize and quantify atherosclerotic plaque. However, the reproducibility of MRI measurements of abdominal and thoracic aortic atherosclerosis has not been reported. Electrocardiogram-gated, T2-weighted, turbo spin echo MRI of the descending thoracic and abdominal aorta was performed on 16 subjects, comprising 10 subjects with multivessel coronary artery disease (CAD) and 6 subjects without angiographic CAD. Three identical MRIs were performed on each subject, with subject repositioning between the second and third scans. Aortic anatomic and plaque measurements were performed in a blinded fashion. Fourteen subjects (88%) had MRI evidence of atherosclerotic plaque on at least one image. Slice plaque burden, plaque area, and plaque perimeter were greater in the CAD group (52% vs. 9%, p = 0.002; 264 vs. 18 mm2, p = 0.009; 159 vs. 15 mm, p = 0.006, respectively). Measurements of total aortic lumen area, lumen circumference, plaque area, and plaque perimeter correlated highly among the three scans (all r = 0.96, all p < 0.001). Measurements of slice-specific aortic lumen area and lumen circumference also correlated highly (all r = 0.98, all p < 0.001). Correlations of slice-specific plaque area and plaque perimeter were significant (all p < 0.001) but less robust (r = 0.62-0.85). These data demonstrate that MRI is a reproducible technique for assessing aortic anatomy and total aortic atherosclerosis, but increased slice density should be considered if serial evaluation of slice-specific data is desired.

Aged↗
PubMed2001

Delayed peripheral nerve degeneration, regeneration, and pain in mice lacking inducible nitric oxide synthase.

Inducible nitric oxide synthase (iNOS) may be a critical factor in the repair of injured tissues. In mice lacking iNOS we observed abnormalities in how the peripheral nerve responds to each of 3 fundamental types of injury: chronic constriction partial nerve injury (a model of neuropathic pain), nerve crush, and nerve transection. In each type of injury, mice lacking iNOS had evidence of a regenerative delay, preceded by slowing of myelinated fiber Wallerian degeneration (WD). In wild-type mice, iNOS immunoreactivity and the presence and upregulation of its mRNA were demonstrated distal to injury, but neither was observed in the knockout mice. Slowed WD was suggested by the abnormal persistence of apparent myelinated fiber profiles distal to the injury zones in mice lacking iNOS compared to wild-type controls. In mice lacking iNOS there were fewer regenerating myelinated fibers, smaller caliber regenerating fibers, and slowed reinnervation of muscle endplates distal to the injury zone. Slowed degeneration was also associated with normal initiation but delayed expression of neuropathic pain. Our findings highlight important relationships among nitric oxide, WD, neuropathic pain, and axon regeneration.

Animals↗
PubMed2001

Referent selection in case-crossover analyses of acute health effects of air pollution.

The case-crossover design was proposed for the study of a transient effect of an intermittent exposure on the subsequent occurrence of a rare acute-onset disease. This design can be an alternative to Poisson time series regression for studying the health effects of fine particulate matter air pollution. Characteristics of time-series of particulate matter, including long-term time trends, seasonal trends, and short-term autocorrelations, require that referent selection in the case-crossover design be considered carefully and adapted to minimize bias. We performed simulations to evaluate the bias associated with various referent selection strategies for a proposed case-crossover study of associations between particulate matter and primary cardiac arrest. Some a priori reasonable strategies were associated with a relative bias as large as 10%, but for most strategies the relative bias was less than 2% with confidence interval coverage within 1% of the nominal level. We show that referent selection for case-crossover designs raises the same issues as selection of smoothing method for time series analyses. In addition, conditional logistic regression analysis is not strictly valid for some case-crossover designs, introducing further bias.

Acute Disease↗
PubMed2001

Microbiology of otitis media in the Paris, France, area from 1987 to 1997.

PURPOSE OF THE STUDY: To investigate epidemiologic trends in the bacteriology of acute otitis media, data were recorded during a 10-year period by the same group of investigators during clinical studies in pediatric outpatients. METHODS: Bacterial samples were obtained before antibiotic treatment from 2149 children (age 3 to 36 months) with acute otitis media. All samples were transported, handled and cultured in the same way throughout the 10-year period. RESULTS: From the study patients 1862 samples of middle ear secretion were collected by tympanocentesis and 287 samples were collected from spontaneous otorrhea occurring within 24 h. Pathogens were isolated from 70% of patients. Pathogens included Haemophilus influenzae (40%), Streptococcus pneumoniae (31%) and Moraxella catarrhalis (8%). The incidence of beta-lactamase-producing H. influenzae was approximately 20% from 1987 to 1989, was approximately 35% from 1990 to 1995 and increased to 60 and 70% during the last 2 years. The rate of S. pneumoniae with decreased susceptibility to penicillin gradually increased from 7% in 1987 to 70% in 1996 and 1997. CONCLUSION: The very high incidence of antimicrobial resistant strains reached during a short period in pediatric acute otitis media in our area, emphasizes the need for frequent epidemiologic studies.

Drug Resistance, Microbial↗
PubMed2001

Development of microsatellite markers in potato and their use in phylogenetic and fingerprinting analyses.

Three genomic libraries were constructed using a mixture of DNA from Solanum phureja Juz. & Buk., and S. chacoense Bitt. Two of the libraries were enriched for ATT and GT repeats (a 27-fold enrichment was achieved). In total, 3500 clones of the conventional library, 1,000 of the library enriched for ATT, and 12,000 of the one enriched for GT were screened with five different repeat motifs, and a total of 18 primer pairs was obtained. Another group of 12 primer pairs was obtained from the SSR-containing sequences in the public databases (18 SSR-containing sequences were utilized). From among 30 newly developed primer pairs, 12 previously published ones, and 12 pairs developed for tomato, 7 were used to identify 12 different potato cultivars and introductions, and 12 were used to study phylogenetic distance among seven wild and cultivated potato species. Two SSR markers were sufficient to discriminate the 12 cultivars. The mean number of alleles per polymorphic locus was 5 for the 12 cultivars and 4.5 for the seven species. The results obtained in this study confirm those achieved in similar studies in other plant species regarding the abundance and use of SSR markers in identifying species and cultivars.

Base Sequence↗
PubMed2001

STAT1 mediates the increased apoptosis and reduced chondrocyte proliferation in mice overexpressing FGF2.

Unregulated FGF receptor signaling results in bone malformations that affect both endochondral and intramembranous ossification, and is the basis for several genetic forms of human dwarfism. FGF signaling inhibits chondrocyte proliferation and we have previously shown that the transcription factor STAT1 mediates the growth inhibitory effect of FGF in vitro. We provide genetic evidence that STAT1 is a modulator of the negative regulation of bone growth by FGF in vivo. We crossed Stat1(-/-) mice with a transgenic mouse line overexpressing human FGF2 (TgFGF). TgFGF mice exhibit phenotypes characterized by chondrodysplasia and macrocephaly, which affect endochondral and intramembranous ossification. We found that the chondrodysplasic phenotype of these mice results both from reduced proliferation and increased apoptosis of growth plate chondrocytes. Loss of STAT1 function in TgFGF mice led to a significant correction of the chondrodysplasic phenotype, but did not affect the skull malformations. The reduced proliferation of TgFGF growth plate chondrocytes, as well as their excessive apoptosis, were restored to near-normal levels in the absence of STAT1 function. Unregulated FGF signaling in TgFGF mice also induced apoptosis in calvarial osteoblasts that was not, however, corrected by the absence of STAT1. Detailed analysis of Stat1(-/-) growth plates uncovered a transient phenotype, characterized by an expansion of the proliferative zone and by acceleration of longitudinal bone growth, that attenuated as the animals grew older. These results document an essential role for STAT1 in FGF-mediated regulation of cell growth that is specific to the epiphyseal growth plate.

Animals↗