PubMed Health⌕ Search

Biomedical subjects

J A Epstein

Publications and source records attributed to J A Epstein.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lbx2, a novel murine homeobox gene related to the Drosophila ladybird genes is expressed in the developing urogenital system, eye and brain.

We describe the cloning, expression pattern, and genomic organization of Lbx2, a murine homologue of the Drosophila and mammalian ladybird genes. Lbx2 includes a homeodomain motif most closely related to those of Lbx1 and the Drosophila ladybird proteins. Lbx2 transcripts are first detected at E10.5 when they are located in the gonadal component of the urogenital ridge. Expression of Lbx2 dramatically increases by E11.5 in the urogenital ridges, and in the cranial surface ectoderm. At later stages, Lbx2 transcripts are expressed in the brain and organs derived from the urogenital ridge, including the gonadal tubercle, kidneys, and adrenal glands. From E14.5 to birth, Lbx2 expression is evident in the developing retinal neuroepithelium and the vibrissa.

Amino Acid Sequence↗
PubMed1999

A six-year follow-up study of determinants of heavy cigarette smoking among high-school seniors.

Most adult cigarette smokers start smoking during adolescence. Few studies, however, have focused on adolescents that are heavy smokers. The present study examined how several risk and protective factors measured during early adolescence were associated with heavy smoking in a sample of high-school seniors. As part of a school-based survey, seventh-grade students (N = 743) reported degrees of experimentation with psychoactive substances and several psychosocial factors deemed to be important in the etiology of smoking. Students were followed-up in the twelfth grade, when 12% (n = 88) smoked a pack of cigarettes or more each day. Logistic regression analyses revealed that heavy smoking was predicted by several earlier variables: poor grades, experimentation with cigarettes or alcohol, a mother or many friends that smoked, and high risk-taking in the seventh grade. Antismoking attitudes and those of one's parents and friends predicted less later heavy smoking in girls only. Implications for smoking prevention are discussed.

Adolescent↗
PubMed1999

Psychosocial predictors of cigarette smoking among adolescents living in public housing developments.

BACKGROUND: Adolescents residing in low-income public housing developments in inner-city regions may be particularly vulnerable to a variety of risk factors associated with cigarette smoking. OBJECTIVE: To elucidate the aetiology of cigarette smoking among adolescents living in public housing developments. DESIGN, SETTING, AND SUBJECTS: We examined predictors of smoking from four domains: background characteristics, social influences, behavioural control, and psychosocial characteristics using a sample of seventh graders (mean age 12.9 years) who reside in public housing developments in New York City (n = 624). The addresses of participants in a larger investigation of the aetiology and prevention of smoking were checked to determine if they lived in one of 335 public housing developments in New York City. All participants living in public housing developments were included in the current study. MAIN OUTCOME MEASURES: African-American and Hispanic students completed questionnaires about their cigarette use, social pressures to smoke, smoking attitudes, smoking knowledge, and smoking resistance skills. Students also provided information on demographic and behavioural control (such as church and school attendance). RESULTS: Logistic regression analyses indicated that social influences from friends and family members predicted smoking. Psychosocial characteristics such as advertising resistance skills, anti-smoking attitudes, and refusal skills lowered the odds of smoking. CONCLUSIONS: These findings suggest that smoking prevention approaches targeted at these young people should increase their awareness of social pressures to smoke, correct misperceptions about the prevalence of smoking among friends, and teach relevant psychosocial skills.

Adolescent↗
PubMed1999

p57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium.

During embryonic development the heart is required to grow in size and cell number, undergo complex morphologic alterations, and function to circulate the blood. Between embryonic d 10.5 (E10.5) and E11.5, cardiac myocytes undergo rapid cell division, resulting in doubling of cardiac mass, while metabolic requirements are increased and contraction force is enhanced. Accelerated cardiomyocyte differentiation is accompanied by a significant increase in trabeculation of ventricular myocardium. Many single gene mutations in the mouse result in a "thinned myocardium" and embryonic lethality between E10.5 and E13.5 secondary to heart failure. This is the case in the Splotch mouse in which a mutation of the Pax3 gene results in neural crest and cardiac defects. Nevertheless, the molecular events governing these important developmental steps remain largely unknown. Here, we describe the use of suppression subtractive hybridization to identify mRNA transcripts whose expression is enhanced during this critical period in normal hearts. These genes encode functions related to maturation of the contractile apparatus, cardiomyocyte differentiation, altered cellular metabolism, and transcriptional regulation. One of the genes that we identified, p57Kip2, encodes a cyclin-dependent kinase inhibitor of the p21 family. We show that p57Kip2 is normally expressed in the inner trabecular layer of the developing heart. In Splotch embryos, expression of p57Kip2 is expanded to encompass the entire thickness of the myocardium. This result and further structural analysis suggests that the myocardial defect of Splotch embryos is associated with precocious cardiomyocyte differentiation.

Amino Acid Sequence↗
PubMed1999

Transgenic rescue of congenital heart disease and spina bifida in Splotch mice.

Pax3-deficient Splotch mice display neural tube defects and an array of neural crest related abnormalities including defects in the cardiac outflow tract, dorsal root ganglia and pigmentation. Pax3 is expressed in neural crest cells that emerge from the dorsal neural tube. Pax3 is also expressed in the somites, through which neural crest cells migrate, where it is required for hypaxial muscle development. Homozygous mutant Splotch embryos die by embryonic day 14. We have utilized the proximal 1.6 kb Pax3 promoter and upstream regulatory elements to engineer transgenic mice reproducing endogenous Pax3 expression in neural tube and neural crest, but not the somite. Over expression of Pax3 in these tissues reveals no discernible phenotype. Breeding of transgenic mice onto a Splotch background demonstrates that neural tube and neural crest expression of Pax3 is sufficient to rescue neural tube closure, cardiac development and other neural crest related defects. Transgenic Splotch mice survive until birth at which time they succumb to respiratory failure secondary to absence of a muscular diaphragm. Limb muscles are also absent. These results indicate that regulatory elements sufficient for functional expression of Pax3 required for cardiac development and neural tube closure are contained within the region 1.6 kb upstream of the Pax3 transcriptional start site. In addition, the single Pax3 isoform used for this transgene is sufficient to execute these developmental processes. Although the extracellular matrix and the environment of the somites through which neural crest migrates is known to influence neural crest behavior, our results indicate that Pax3-deficient somites are capable of supporting proper neural crest migration and function suggesting a cell autonomous role for Pax3 in neural crest.

Animals↗
PubMed1999

Pax3 functions in cell survival and in pax7 regulation.

In developing vertebrate embryos, Pax3 is expressed in the neural tube and in the paraxial mesoderm that gives rise to skeletal muscles. Pax3 mutants develop muscular and neural tube defects; furthermore, Pax3 is essential for the proper activation of the myogenic determination factor gene, MyoD, during early muscle development and PAX3 chromosomal translocations result in muscle tumors, providing evidence that Pax3 has diverse functions in myogenesis. To investigate the specific functions of Pax3 in development, we have examined cell survival and gene expression in presomitic mesoderm, somites and neural tube of developing wild-type and Pax3 mutant (Splotch) mouse embryos. Disruption of Pax3 expression by antisense oligonucleotides significantly impairs MyoD activation by signals from neural tube/notochord and surface ectoderm in cultured presomitic mesoderm (PSM), and is accompanied by a marked increase in programmed cell death. In Pax3 mutant (Splotch) embryos, MyoD is activated normally in the hypaxial somite, but MyoD-expressing cells are disorganized and apoptosis is prevalent in newly formed somites, but not in the neural tube or mature somites. In neural tube and somite regions where cell survival is maintained, the closely related Pax7 gene is upregulated, and its expression becomes expanded into the dorsal neural tube and somites, where Pax3 would normally be expressed. These results establish that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesoderm and in repression of Pax7 during neural tube and somite development.

Animals↗
PubMed1999

Impact of social influences and problem behavior on alcohol use among inner-city Hispanic and black adolescents.

OBJECTIVE: Inner-city black and Hispanic adolescents might be at great risk for alcohol use. Yet the etiology of drinking among these adolescents receives little attention. The purpose of this study was to examine the impact of social influences and problem behavior on alcohol use among Hispanic and black adolescents. The impact of these factors was also tested separately for girls and boys to determine the differences in etiology of alcohol use depending on gender. METHOD: A large sample of black and Hispanic seventh-grade students (N = 4,847, 52% female) self-reported alcohol use, demographic characteristics (gender, family structure, age, ethnicity and socioeconomic status), social influences to drink (peer norms, adult norms, their friends' use, their mother's use, their father's use, their siblings' use, and perceived availability of alcohol), and problem behaviors (cigarette smoking, marijuana use, getting into trouble). Teams of three to five data collectors administered the questionnaire following standardized protocol. These data were collected in class during a regular 40-minute period. RESULTS: Logistic regressions indicated that social influences to drink from friends, peers, and family and problem behaviors including cigarette smoking and marijuana use were related to alcohol use across and within gender. Getting into trouble predicted drinking for boys but not girls. CONCLUSIONS: Based on these findings, adolescent alcohol prevention programs need to include an awareness of the many social influences to drink, modify incorrectly perceived peer norms for drinking, involve family members in the prevention program and address an array of problem behaviors within one prevention intervention.

Adolescent↗
PubMed1998

Gscl, a gene within the minimal DiGeorge critical region, is expressed in primordial germ cells and the developing pons.

Gscl, a paired-type homeobox gene, has been implicated in the pathology of DGS/VCFS by virtue of its genomic location and its structural similarity to the Gsc gene family. Immunohistochemical and in situ studies were performed to examine the expression pattern of this gene during embryonic development. A polyclonal antibody, generated to the full-length protein and shown to be specific for GSCL by both Western blotting and immunofluorescence, was used for immunohistochemical localization. Both in situ and antibody staining localized GSCL expression to a cluster of cells in the pons region of the developing brain. This GSCL expression pattern showed partial overlap with that of Pax6. More detailed immunohistochemistry revealed the GSCL in primordial germ cells during migration from the epithelium of the hindgut and later as they colonize the developing gonads. GSCL was not detected in tissues affected in DGS/VCSF.

3T3 Cells↗
PubMed1998

Ethnic and gender differences in smoking prevalence among a longitudinal sample of inner-city adolescents.

PURPOSE: To determine if ethnic and gender differences in smoking (lifetime prevalence and 30-day prevalence) exist among a cohort of Asian, black, Hispanic, and white inner-city adolescents during the 3-year middle school period. METHODS: Students in 22 urban schools completed self-report questionnaires and provided carbon monoxide breath samples at three annual assessments. Chi-square analyses were conducted to test for associations between ethnic group (Asian, black, Hispanic, and white) and smoking and to test for gender differences in smoking within each ethnic group. Additional analyses examined differences in smoking between two Hispanic subgroups (Puerto Rican and Dominican). RESULTS: Ethnicity was associated with lifetime smoking prevalence at all three assessment points but was only associated with 30-day smoking prevalence at the 2-year follow-up. However, there were no differences in smoking between Puerto Rican and Dominican youth. Black girls reported higher lifetime smoking prevalence than black boys at all three assessments. At the 2-year follow-up, Asian boys reported higher lifetime smoking prevalence than Asian girls; Hispanic girls reported higher 30-day prevalence than Hispanic boys. CONCLUSIONS: White and Hispanic adolescents were at higher risk for smoking relative to Asian and black adolescents. With the exception of white youth, gender differences were found within each ethnic group.

Adolescent↗
PubMed1998

Psychosocial determinants of alcohol use among minority youth living in public housing developments.

Youth residing in low income, inner city, public housing developments might be extremely vulnerable to psychosocial risk factors associated with alcohol use. In this study, we developed and tested a model of alcohol etiology with 624 African-American and Hispanic 7th graders residing in public housing developments. The students completed questionnaires concerning their alcohol use, social influences on their drinking, their drinking attitudes and knowledge, their psychosocial skills, and demographic and behavioral control information. Logistic regression analyses indicated that social influences from adults, friends, and family members predicted alcohol use. Individual psychosocial characteristics, e.g., drinking refusal, lowered the odds of drinking. These findings imply that effective prevention approaches targeting minority urban youths residing in public housing developments should provide them with an awareness of social influences to drink, correct misperceptions concerning the prevalence of drinking, and train them in relevant psychosocial skills.

Adolescent↗
PubMed1998

Tumor-specific PAX3-FKHR transcription factor, but not PAX3, activates the platelet-derived growth factor alpha receptor.

The t(2;13) chromosomal translocation occurs at a high frequency in alveolar rhabdomyosarcoma, a common pediatric tumor of muscle. This translocation results in the production of a chimeric fusion protein derived from two developmentally regulated transcription factors, PAX3 and FKHR. The two DNA binding modules, the paired domain and the homeodomain, of PAX3 are fused in frame to the transactivation domain of FKHR. Previously, tumor-specific PAX3-FKHR has been shown to bind to DNA sequences normally recognized by wild-type PAX3 and to exhibit relatively enhanced transcriptional activity. The DNA binding sites used to demonstrate that PAX3-FKHR is a more potent transcriptional activator than PAX3 have included recognition sequences for the paired domain of PAX3. In this report, we demonstrate the ability of PAX3-FKHR to activate the product of a growth control gene, platelet-derived growth factor alpha receptor (PDGFalphaR), by recognizing a paired-type homeodomain binding site located in the PDGFalphaR promoter. PAX3 alone cannot mediate transcriptional activation of this promoter under the conditions tested. This provides the first evidence that chromosomal translocation results in altered target gene specificity of PAX3-FKHR and suggests a transcriptional target that may play a significant role in oncogenic activity and rhabdomyosarcoma development.

Animals↗
PubMed1998

Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart.

Endocardial cushions are the precursors of the cardiac valves and form by a process of epithelial-mesenchymal transformation. Secreted growth factors from myocardium induce endocardial cells to transform into mesenchyme and invade the overlying extracellular matrix. Here, we show that the product of the Nf1 neurofibromatosis gene is required to regulate this event. In the absence of neurofibromin, mouse embryo hearts develop overabundant endocardial cushions due to hyperproliferation and lack of normal apoptosis. Neurofibromin deficiency in explant cultures is reproduced by activation of ras signaling pathways, and the Nf1(-/-) mutant phenotype is prevented by inhibiting ras in vitro. These results indicate that neurofibromin normally acts to modulate epithelial-mesenchymal transformation and proliferation in the developing heart by down regulating ras activity.

Animals↗
PubMed1998

Adolescent cigarette smoking: prevalence, causes, and intervention approaches.

Cigarette smoking continues to be a major public health problem that specifically affects the adolescent population. This chapter discusses current prevalence rates, recent trends, and the etiology of adolescent smoking, as well as strategies for preventing or reducing it. The authors highlight the prevention approaches demonstrated to effectively influence smoking behavior, such as those that teach adolescents social resistance skills and antismoking norms alone or in combination with teaching overall personal and social skills.

Adolescent↗
PubMed1997

Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function.

Vertebrate limb tendons are derived from connective cells of the lateral plate mesoderm. Some of the developmental steps leading to the formation of vertebrate limb tendons have been previously identified; however, the molecular mechanisms responsible for tendinous patterning and maintenance during embryogenesis are largely unknown. The eyes absent (eya) gene of Drosophila encodes a novel nuclear protein of unknown molecular function. Here we show that Eya1 and Eya2, two mouse homologues of Drosophila eya, are expressed initially during limb development in connective tissue precursor cells. Later in limb development, Eya1 and Eya2 expression is associated with cell condensations that form different sets of limb tendons. Eya1 expression is largely restricted to flexor tendons, while Eya2 is expressed in the extensor tendons and ligaments of the phalangeal elements of the limb. These data suggest that Eya genes participate in the patterning of the distal tendons of the limb. To investigate the molecular functions of the Eya gene products, we have analyzed whether the highly divergent PST (proline-serine-threonine)-rich N-terminal regions of Eya1-3 function as transactivation domains. Our results demonstrate that Eya gene products can act as transcriptional activators, and they support a role for this molecular function in connective tissue patterning.

Animals↗