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D Levy

Publications and source records attributed to D Levy.

At least 91 records · Page 5Linked to original sources
PubMed2000

Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study.

Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100. 5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.

Amino Acid Sequence↗
PubMed2000

Evidence for a gene influencing blood pressure on chromosome 17. Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the framingham heart study.

Hypertension is a leading cause of morbidity and mortality. Efforts to identify hypertension genes have focused on 3 approaches: mendelian disorders, candidate genes, and genome-wide scans. Thus far, these efforts have not identified genes that contribute substantively to overall blood pressure (BP) variation in the community. A 10-centiMorgan (cM) density genome-wide scan was performed in the largest families from 2 generations of Framingham Heart Study participants. Heritability and linkage for long-term mean systolic and diastolic BP phenotypes were analyzed by use of SOLAR software. Heritability estimates were based on BP measurements in 1593 families. Genotyping was performed on 1702 subjects from 332 large families, and BP data were available for 1585 (93%) genotyped subjects who contributed 12 588 longitudinal BP observations. The mean age was 47 years, and mean BP was 127/80 (systolic/diastolic) mm Hg. Long-term systolic and diastolic BP phenotypes had high heritability estimates, 0.57 and 0.56, respectively. For systolic BP, multipoint log-of-the-odds (LOD) scores >2.0 were located on chromosome 17 at 67 cM (LOD 4.7, P=0.0000016) and 94 cM (LOD 2.2). For diastolic BP, LOD scores >2.0 were identified on chromosome 17 (74 cM, LOD 2.1) and chromosome 18 (7 cM, LOD 2.1). Using a genome-wide scan, we found strong evidence for a BP quantitative trait locus on chromosome 17. Follow-up studies are warranted to identify the gene or genes in this quantitative trait locus that influence BP. Such knowledge could extend our understanding of the genetic basis of essential hypertension and have implications for the evaluation and treatment of patients with high BP.

Adolescent↗
PubMed2000

Differential control of systolic and diastolic blood pressure : factors associated with lack of blood pressure control in the community.

Data from the Third National Health and Nutrition Examination Survey, phase 2 (1991 to 1994), indicate that among hypertensive individuals in the United States, 53.6% are treated and only 27.4% are controlled to goal levels. We sought to determine whether poor hypertension control is due to lack of systolic or diastolic blood pressure control, or both. We studied Framingham Heart Study participants examined between 1990 and 1995 and determined rates of control to systolic goal (<140 mm Hg), diastolic goal (<90 mm Hg), or both (systolic <140 and diastolic <90 mm Hg). Of 1959 hypertensive subjects (mean age 66 years, 54% women), 32.7% were controlled to systolic goal, 82.9% were controlled to diastolic goal, and only 29.0% were controlled to both. Among the 1189 subjects who were receiving antihypertensive therapy (60.7% of all hypertensive subjects), 49.0% were controlled to systolic goal, 89.7% were controlled to diastolic goal, and only 47.8% were controlled to both. Thus, poor systolic blood pressure control was overwhelmingly responsible for poor rates of overall control to goal. Covariates associated with lack of systolic control in treated subjects included older age (OR for age 61 to 75 years, 2.43, 95% CI 1.79 to 3.29; OR for age >75 years, 4.34, 95% CI 3.10 to 6.09), left ventricular hypertrophy (OR 1.63, 95% CI 1.04 to 2.54), and obesity (OR for body mass index >/=30 versus <25 kg/m(2), 1.49, 95% CI 1.08 to 2.06). In this community-based sample of middle-aged and older subjects, overall rates of hypertension control were remarkably similar to those in the Third National Health and Nutrition Examination Survey. Poor blood pressure control was overwhelmingly due to lack of systolic control, even among treated subjects. Therefore, clinicians and policymakers should place greater emphasis on the achievement of goal systolic levels in all hypertensive patients, especially those who are older or obese or have target organ damage.

Aged↗
PubMed2000

Bone mineral density and risk of incident and progressive radiographic knee osteoarthritis in women: the Framingham Study.

OBJECTIVE: To examine the relations of bone mineral density (BMD) and change in BMD to risk of incident and progressive radiographic knee osteoarthritis (OA) in a longitudinal cohort study. METHODS: Female participants aged 63 to 91 years (mean age 71) in the Framingham Study received anteroposterior weight bearing knee radiographs at biennial examinations 18 (1983-85) and 22 (1992-93). Knee radiographs were given scores for global severity of OA (Kellgren-Lawrence scale: range 0 to 4) and for the presence of osteophytes and joint space narrowing (range 0 to 3). Femoral neck BMD was assessed using dual photon absorptiometry at examination 20 and dual x-ray absorptiometry at examination 22. We examined the relations of BMD at examination 20 and its change between examination 20 and examination 22 to incident and progressive knee OA, as well as to worsening of individual radiographic features adjusting for age, body mass index, and other potential confounding factors. RESULTS: In total, 473 women (ages 63 to 91 yrs) had complete assessments. Over 8 years of followup, risk of incident radiographic knee OA increased from 5.6% among women in the lowest age-specific quartile of BMD to 14.2, 10.3, and 11.8% among women in the 2nd, 3rd, and highest quartiles, respectively. Multivariate adjusted OR of incident OA for each increase quartile of BMD were 1.0, 2.5, 2.0, and 2.3, respectively (p for trend = 0.222). This was mainly reflected in an increased risk of osteophyte development. However, risk of progressive OA decreased from 34.4 to 22.0, 20.3, and 18.9% as BMD increased. Compared to those in the lowest quartile of BMD, adjusted OR for progressive disease were 0.3, 0.2, and 0.1 among women in the 2nd, 3rd, and highest quartiles (p for trend <0.001), respectively, mainly due to its effect on lowering the risk of joint space loss. Compared to those who lost BMD >0.04 g/cm2 over the followup period, women who gained BMD were at increased risk of incident but at a significantly decreased risk of progressive knee OA. BMD change was not associated with osteophyte development, but gain in BMD lowered the risk of joint space loss. CONCLUSION: High BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee OA. The protective effect was mainly through its influence on reducing the risk of joint space loss. Our results offer insights into how bone may affect the course of the most common joint disease, and thus may have potential therapeutic implications.

Absorptiometry, Photon↗
PubMed2000

Stroke: a case review.

Stroke is indicated by an abrupt manifestation of neurologic deficits secondary to an ischemic or hemorrhagic insult to a region of the brain. Stroke is ranked as the third leading cause of death in the United States, affects more than 730,000 individuals per year, and accounts for 160,000 deaths annually. Approximately $40 billion is spent annually for health care treating stroke victims. This case report shows that despite the use of antithrombotic and/or antiplatelet aggregating drugs, the key to stroke management is primary prevention.

Aged↗
PubMed2000

A case-crossover analysis of fine particulate matter air pollution and out-of-hospital sudden cardiac arrest.

Numerous recent epidemiologic studies report increases in the daily incidence of cardiovascular disease mortality and morbidity related to increases in daily levels of fine particulate matter (PM)* air pollution. This study sought to evaluate the possible association between the occurrence of out-of-hospital sudden cardiac arrest (SCA) and daily PM levels in the Seattle metropolitan area. The underlying hypothesis was that PM exposure may act as a cardiovascular trigger for SCA. A case-crossover study was conducted among 362 SCA cases identified by paramedics from October 1988 through June 1994. Cases were King County WA residents who were married, aged 25 to 74 years at the time of their SCA, with no prior history of clinically recognized heart disease or other life-threatening comorbid conditions. Daily averages of regional PM monitoring data for nephelometry measures of PM (reported in units of bsp, referred to as coefficient of light scattering) and PM10 (particulate matter 10 microm or smaller in aerodynamic diameter) from three monitoring sites were used as indicators of exposure. In the case-crossover analysis, PM levels during index times of cases within the five days preceding an SCA were compared with PM levels at referent days, defined as the same days of the week during the month of SCA occurrence. Lag periods for index days of 0 to 5 days were investigated. The estimated relative risk (RR) at a lag of 1 day for an interquartile range (IQR) change in nephelometry (0.51 bsp) was 0.893 (95% confidence interval [CI] 0.779-1.024). Varying the lag period had only minimal change on the observed association. The estimated relative risk at a lag of 1 day for an IQR change of PM10 (19.3 microg/m3) was 0.868 (95% CI 0.744-1.012). There was no evidence of confounding by ambient daily exposures to carbon monoxide or sulfur dioxide. Analysis of effect modification by individual-level variables, including age, cigarette smoke exposure, physical activity, and other risk or protective factors for cardiovascular disease did not reveal any susceptible subgroups. The null results of this study may be due to several factors; these include: the highly selected nature of this SCA case series; the fact that cases were free of prior clinically recognized heart disease or major life-threatening comorbidity; and the possibility that PM exposures at the relatively low levels seen in the Seattle metropolitan area do not trigger cardiovascular toxic mechanisms that culminate in SCA.

Adult↗
PubMed1999

Temporal trends in event rates after Q-wave myocardial infarction: the Framingham Heart Study.

BACKGROUND: Short-term (<30 day) mortality after Q-wave myocardial infarction (MI) has declined over the decades, but it is unclear if rates of long-term sequelae after Q-wave MI have improved. METHODS AND RESULTS: In 546 Framingham Heart Study subjects (388 men with a mean age of 60 years; 158 women with a mean age of 69 years) with an initial recognized Q-wave MI from 1950 through 1989, we investigated time trends in risk for coronary heart disease (CHD) death (n=199), all-cause mortality (n=287), reinfarction (n=108), and congestive heart failure (CHF; n=121). With 1950 through 1969 as the reference period, hazards ratios (HRs) for these outcomes were determined for the 1970s and 1980s. Trend analyses across the 3 time periods were performed for each outcome. Compared with the 1950 through 1969 reference period, the HRs for CHD death were lower in subsequent decades (1970 through 1979: HR, 0.69; 95% CI, 0.49 to 0.98; 1980 through 1989: HR, 0.48; 95% CI, 0.33 to 0.72). All-cause mortality also declined (1970 through 1979: HR, 0.70; 95% CI, 0.0.52 to 0.94; 1980 through 1989: HR, 0.59; 95% CI, 0.43 to 0.81). There were no significant temporal changes in the risks for recurrent MI or CHF. CONCLUSIONS: Substantial reductions in risk of CHD death and all-cause mortality occurred over these 4 decades, coincident with improvements in post-MI therapies. The absence of a decline in CHF incidence may be due to improved post-MI survival of individuals with depressed left ventricular systolic function who are at high risk for CHF.

Adult↗
PubMed1999

Cross-classification of JNC VI blood pressure stages and risk groups in the Framingham Heart Study.

BACKGROUND: The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are stratified into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B (> or =1 associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease). OBJECTIVE: To examine the prevalence of risk groups and blood pressure stages in a community-based sample. METHODS: We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups. RESULTS: In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with high-normal blood pressure or hypertension, only 2.4% (all women) were in risk group A, 59.3% were in group B, and 38.2% were in group C. In the high-normal or hypertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended. CONCLUSIONS: These results provide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice.

Adult↗
PubMed1999

Membrane topology and cell surface targeting of microsomal epoxide hydrolase. Evidence for multiple topological orientations.

Microsomal epoxide hydrolase (mEH) is a bifunctional membrane protein that plays a central role in the metabolism of xenobiotics and in the hepatocyte uptake of bile acids. Numerous studies have established that this protein is expressed both in the endoplasmic reticulum and at the sinusoidal plasma membrane. Preliminary evidence has suggested that mEH is expressed in the endoplasmic reticulum (ER) membrane with two distinct topological orientations. To further characterize the membrane topology and targeting of this protein, an N-glycosylation site was engineered into mEH to serve as a topological probe for the elucidation of the cellular location of mEH domains. The cDNAs for mEH and this mEH derivative (mEHg) were then expressed in vitro and in COS-7 cells. Analysis of total expressed protein in these systems indicated that mEHg was largely unglycosylated, suggesting that expression in the ER was primarily of a type I orientation (Ccyt/Nexo). However, analysis, by biotin/avidin labeling procedures, of mEHg expressed at the surface of transfected COS-7 cells, showed it to be fully glycosylated, indicating that the topological form targeted to this site originally had a type II orientation (Cexo/Ncyt) in the ER. The surface expression of mEH was also confirmed by confocal fluorescence scanning microscopy. The sensitivity of mEH topology to the charge at the N-terminal domain was demonstrated by altering the net charge over a range of 0 to +3. The introduction of one positive charge led to a significant inversion in mEH topology based on glycosylation site analysis. A truncated form of mEH lacking the N-terminal hydrophobic transmembrane domain was also detected on the extracellular surface of transfected COS-7 cells, demonstrating the existence of at least one additional transmembrane segment. These results suggest that mEH may be integrated into the membrane with multiple transmembrane domains and is inserted into the ER membrane with two topological orientations, one of which is targeted to the plasma membrane where it mediates bile acid transport.

Amino Acid Sequence↗
PubMed1999

Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study.

BACKGROUND: Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. METHODS AND RESULTS: We studied 1924 men and women between 50 and 79 years of age at baseline with no clinical evidence of CHD and not taking antihypertensive drug therapy. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relations between blood pressure components and CHD risk over a 20-year follow-up. The association with CHD risk was positive for SBP, DBP, and PP, considering each pressure individually; of the 3, PP yielded the largest chi(2) statistic. When SBP and DBP were jointly entered into the multivariable model, the association with CHD risk was positive for SBP (HR, 1.22; 95% CI, 1.15 to 1.30) and negative for DBP (HR, 0. 86; 95% CI, 0.75 to 0.98). Four subgroups were defined according to SBP levels (<120, 120 to 139, 140 to 159, and >/=160 mm Hg). Within each subgroup, the association with CHD risk was negative for DBP and positive for PP. A cross-classification of SBP-DBP levels confirmed these results. CONCLUSIONS: In the middle-aged and elderly, CHD risk increased with lower DBP at any level of SBP>/=120 mm Hg, suggesting that higher PP was an important component of risk. Neither SBP nor DBP was superior to PP in predicting CHD risk.

Aged↗
PubMed1999

Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study.

BACKGROUND: Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain. OBJECTIVE: To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes. DESIGN: Community-based, prospective observational study. SETTING: Framingham, Massachusetts. PATIENTS: 6763 Framingham Heart Study participants (mean age, 47 years). MEASUREMENTS: Serum uricacid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile. RESULTS: During 117,376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes. CONCLUSIONS: These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.

Age Distribution↗
PubMed1999

Prevalence and clinical outcome of mitral-valve prolapse.

BACKGROUND: Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [+/-SD] age, 54.7+/-10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study. METHODS: Classic mitral-valve prolapse was defined as superior displacement of the mitral leaflets of more than 2 mm during systole and as a maximal leaflet thickness of at least 5 mm during diastasis, and nonclassic prolapse was defined as displacement of more than 2 mm, with a maximal thickness of less than 5 mm. RESULTS: A total of 84 subjects (2.4 percent) had mitral-valve prolapse: 47 (1.3 percent) had classic prolapse, and 37 (1.1 percent) had nonclassic prolapse. Their age and sex distributions were similar to those of the subjects without prolapse. None of the subjects with prolapse had a history of heart failure, one (1.2 percent) had atrial fibrillation, one (1.2 percent) had cerebrovascular disease, and three (3.6 percent) had syncope, as compared with unadjusted prevalences of these findings in the subjects without prolapse of 0.7, 1.7, 1.5, and 3.0 percent, respectively. The frequencies of chest pain, dyspnea, and electrocardiographic abnormalities were similar among subjects with prolapse and those without prolapse. The subjects with prolapse were leaner (P<0.001) and had a greater degree of mitral regurgitation than those without prolapse, but on average the regurgitation was classified as trace or mild. CONCLUSIONS: In a community based sample of the population, the prevalence of mitral-valve prolapse was lower than previously reported. The prevalence of adverse sequelae commonly associated with mitral-valve prolapse in studies of patients referred for that diagnosis was also low.

Adult↗
PubMed1999

An 8-A projected structure of FhuA, A "ligand-gated" channel of the Escherichia coli outer membrane.

The structure of FhuA, a siderophore and phage receptor in the outer membrane of Escherichia coli, has been investigated by electron crystallography. Bidimensional crystals of hexahistidine-tagged FhuA protein solubilized in N,N-dimethyldodecylamine-N-oxide were produced after detergent removal with polystyrene beads. Frozen-hydrated crystals (unit cell dimensions of a = 124 A, b = 98 A, gamma = 90 degrees ) exhibited a p22121 plane group symmetry. A projection map at 8 A resolution showed the presence of dimeric ring-like structures with an elliptical shape (48 x 40 A). Each monomer was composed of a ring of densities with a radial width of 8-10 A corresponding to a cylinder of beta sheets. Few densities are present inside the barrel, leaving a central channel approximately 25 A in diameter. A projection map of FhuA at 15 A resolution, which was calculated from negatively stained preparations, demonstrated that most of the central channel was masked by extramembrane domains. This map also revealed an asymmetric distribution of extramembrane domains in FhuA, with large domains located mainly on one side of the molecule. Comparison with density maps derived from recent atomic structure allowed further interpretation of the electron microscopy projection structures with regard to long hydrophilic loops governing the selectivity and opening of the channel.

Bacterial Outer Membrane Proteins↗
PubMed1999

Profile for estimating risk of heart failure.

CONTEXT: We devised a risk appraisal function to assess the hazard of heart failure in persons who are predisposed by coronary disease, hypertension, or valvular heart disease. OBJECTIVE: To provide general practitioners and internists with a cost-effective method to select people at high risk who are likely to have impaired left ventricular systolic function and may therefore require further evaluation and aggressive preventive measures. METHODS: The routinely measured risk factors used in constructing the heart failure profile include age, electrocardiographic left ventricular hypertrophy, cardiomegaly on chest x-ray film, heart rate, systolic blood pressure, vital capacity, diabetes mellitus, evidence of myocardial infarction, and valvular disease or hypertension. Based on 486 heart failure cases during 38 years of follow-up, 4-year probabilities of failure were computed using the pooled logistic regression model for each sex; a simple point score system was employed. A multivariate profile was also produced without the vital capacity or chest x-ray film because these may not be readily available in some clinical settings. RESULTS: Using the risk factors that make up the multivariate risk formulation-derived from ordinary office procedures-the probability of developing heart failure can be estimated and compared with the average risk for persons of the same age and sex. Using this risk profile, 60% of events in men and 73% in women occurred in subjects in the top quintile of multivariate risk. CONCLUSIONS: Using this multivariate risk formulation, it is possible to identify high-risk candidates for heart failure who are likely to have a substantial yield of positive findings when tested for objective evidence of presymptomatic left ventricular dysfunction. The risk profile may also identify candidates who are at high risk for heart failure because of multiple, marginal risk factor abnormalities that might otherwise be overlooked.

Aged↗
PubMed1999

FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway.

Several genetic forms of human dwarfism have been linked to activating mutations in FGF receptor 3, indicating that FGF signaling has a critical role in chondrocyte maturation and skeletal development. However, the mechanisms through which FGFs affect chondrocyte proliferation and differentiation remain poorly understood. We show here that activation of FGF signaling inhibits chondrocyte proliferation both in a rat chondrosarcoma (RCS) cell line and in primary murine chondrocytes. FGF treatment of RCS cells induces phosphorylation of STAT-1, its translocation to the nucleus, and an increase in the expression of the cell-cycle inhibitor p21WAF1/CIP1. We have used primary chondrocytes from STAT-1 knock-out mice to provide genetic evidence that STAT-1 function is required for the FGF mediated growth inhibition. Furthermore, FGF treatment of metatarsal rudiments from wild-type and STAT-1(-/-) murine embryos produces a drastic impairment of chondrocyte proliferation and bone development in wild-type, but not in STAT-1(-/-) rudiments. We propose that STAT-1 mediated down regulation of chondrocyte proliferation by FGF signaling is an homeostatic mechanism which ensures harmonious bone development and morphogenesis.

3T3 Cells↗