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Biomedical subjects

J A Epstein

Publications and source records attributed to J A Epstein.

At least 73 records · Page 4Linked to original sources

Pax3 modulates expression of the c-Met receptor during limb muscle development.

Pax3 is a transcription factor whose expression has been used as a marker of myogenic precursor cells arising in the lateral somite destined to migrate to and populate the limb musculature. Accruing evidence indicates that the embryologic origins of axial and appendicular muscles are distinct, and limb muscle abnormalities in both mice and humans harboring Pax3 mutations support this distinction. The mechanisms by which Pax3 affects limb muscle development are unknown. The tyrosine kinase receptor for hepatocyte growth factor/scatter factor encoded by the c-met protooncogene is also expressed in limb muscle progenitors and, like Pax-3, is required in the mouse for limb muscle development. Here, we show that c-met expression is markedly reduced in the lateral dermomyotome of Splotch embryos lacking Pax3. We show that Pax3 can stimulate c-met expression in cultured cells, and we identify a potential Pax3 binding site in the human c-MET promoter that may contribute to direct transcriptional regulation. In addition, we have found that several cell lines derived from patients with rhabdomyosarcomas caused by a t(2;13) chromosomal translocation activating PAX3 express c-MET, whereas those rhabdomyosarcoma cell lines examined without the translocation do not. These results are consistent with a model in which Pax3 modulates c-met expression in the lateral dermomyotome, a function that is required for the appropriate migration of these myogenic precursors to the limb where the ligand for c-met (hepatocyte growth factor/scatter factor) is expressed at high levels.

Animals↗

Ethnic-racial differences in psychological stress related to gay lifestyle among HIV-positive men.

To examine whether there were any ethnic-racial differences among 144 HIV-infected gay men (47 Caucasian, 48 African-American, and 49 Puerto Rican) on psychological stressors related to the gay lifestyle, responses to the Gay Lifestyle Hassles scale were analyzed. The African-American and Puerto Rican men reported significantly higher scores on frequency of Gay lifestyle Hassles and cumulated severity of Gay Lifestyle Hassles over-all than Caucasian men. The results suggest that HIV-infected ethnic-minority gay men were more prone to psychological stress related to the gay lifestyle than HIV-infected Caucasian gay men, which may have negative consequences for their mental and physical health.

Adaptation, Psychological↗

Validation of an acculturation measure for Hispanic adolescents.

Based on the continuing growth and youthfulness of the Hispanic population in the United States, valid cultural measures are needed for Hispanic adolescents. Hispanics living in this country experience acculturation or cultural change during their exposure to American culture. A matched sample of 994 Hispanic students and their parents completed acculturation measures. Scores on a 10-item acculturation scale completed by the adolescents' parents correlated significantly .49 with a single-item rating, a measure of acculturation by adolescents. This finding supports construct validity for a measure of language use as an index of linguistic acculturation for Hispanic adolescents.

Acculturation↗

Lying in everyday life.

In 2 diary studies of lying, 77 college students reported telling 2 lies a day, and 70 community members told 1. Participants told more self-centered lies than other-oriented lies, except in dyads involving only women, in which other-oriented lies were as common as self-centered ones. Participants told relatively more self-centered lies to men and relatively more other-oriented lies to women. Consistent with the view of lying as an everyday social interaction process, participants said that they did not regard their lies as serious and did not plan them much or worry about being caught. Still, social interactions in which lies were told were less pleasant and less intimate than those in which no lies were told.

Adolescent↗

Pax3 inhibits myogenic differentiation of cultured myoblast cells.

Pax3 is an evolutionarily conserved transcription factor expressed in the lateral dermomyotome, a region that gives rise to limb muscle progenitors. Mutations in Pax-3 account for the mouse mutant Splotch which develops without limb musculature. We demonstrate that Pax3 can inhibit myogenic differentiation of C2C12 myoblasts normally induced by exposure to low serum. Specific missense mutations that affect the DNA binding characteristics of the two distinct DNA binding domains of Pax3 abolish this effect. Furthermore, we show that Pax3 can inhibit myogenic differentiation of 10T1/2 fibroblasts transfected with MyoD, but not of 10T1/2 cells transfected with myogenin. This anti-myogenic property is shared by a PAX3-forkhead fusion protein resulting from a t(2;13) chromosomal translocation found in pediatric alveolar rhabdomyosarcomas. These results suggest that Pax3 may suppress the terminal differentiation of migrating limb myoblasts and that the PAX3-forkhead fusion may contribute to the phenotype of alveolar rhabdomyosarcoma by preventing terminal differentiation.

Amino Acid Sequence↗

The role of social factors and individual characteristics in promoting alcohol use among inner-city minority youths.

OBJECTIVE: During seventh grade, many adolescents initiate alcohol use yet school drop-out rates are still low. Therefore, this is an ideal period of adolescence to examine predictors of alcohol use. The purpose of this study was to elucidate the etiology of alcohol use among an understudied population: disadvantaged inner-city minority youths. Specifically, we attempted to develop as complete a model of predictors of alcohol use as possible from three domains: background characteristics, social influences to drink and individual characteristics. METHOD: To explore alcohol use of youths who are living in poverty and are members of minority groups, New York City public schools from districts known to have predominantly minority student bodies with low socioeconomic status (SES) were identified. Self-reports of alcohol use and data concerning background, social environmental and individual characteristics hypothesized to promote drinking alcohol were collected from black and Hispanic seventh graders (N = 757). RESULTS: Logistic regression analyses indicated that social influences from friends, peers and parents predicted alcohol use. Most interestingly, the drinking status of the person the respondent most admired was related to drunkenness and future alcohol use. Individual characteristics, such as health-related knowledge concerning alcohol use and antidrinking attitudes, lowered the odds of drinking. CONCLUSIONS: These findings imply that effective prevention programs targeting inner-city minority youths should provide students with an awareness of the social influences to drink, provide them with positive role models and correct misperceptions about the prevalence of drinking among friends and peers.

Adolescent↗

Social and personal factors in marijuana use and intentions to use drugs among inner city minority youth.

Limited information is available about the etiology of illicit drug use among minority youth. This study examined predictors of marijuana use and intentions to use marijuana, cocaine/crack, and other drugs for African-American and Hispanic seventh graders (N = 757). Self-reports of marijuana use and intentions to use drugs were collected along with data concerning background, social environmental, and individual characteristics hypothesized to be related to drug use. Results indicated that social influences, including adults, friends, and the most admired person's marijuana use, predicted marijuana use. Individual characteristics, such as a lack of knowledge about the prevalence and negative social consequences of marijuana use, positive attitudes toward marijuana use, and inadequate social, communication, and refusal skills increased suspectability to marijuana use. Lack of self-efficacy was related to intentions to use cocaine and other drugs. Implications of these findings are discussed with respect to the development of effective prevention programs.

Achievement↗

Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.

Vertebrate Pax proteins share a conserved 128-amino-acid DNA-binding motif, the paired domain. The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain. This protein, which arises by alternative mRNA splicing, exhibits unique DNA-binding properties. Unlike other paired domains, which bind DNA predominantly by their amino termini, the extended Pax6 paired domain interacts with DNA exclusively through its carboxyl terminus. This property can be stimulated by deletion of 30 amino-terminal residues from the Pax6 or Pax2 paired domains. Thus, the insertion acts as a molecular toggle to unmask the DNA-binding potential of the carboxyl terminus. The functional nonequivalence of the two Pax6 proteins is underscored by a T-->C mutation at position -3 of the alternative splice acceptor site that changes the ratio of the two isoforms and causes a distinct human ocular syndrome.

Alternative Splicing↗

Determinants of intentions of Junior High School students to become sexually active and use condoms: implications for reduction and prevention of AIDS risk.

The purpose of this study was to examine factors associated with young adolescents' increased risk for AIDS. A multiethnic sample of 303 seventh-grade students in three schools in the greater New York area completed questionnaires assessing their basic demographic characteristics (gender and ethnicity), AIDS knowledge, substance use (cigarette smoking, alcohol use), and decision-making skills. AIDS knowledge, substance use, decision-making skills, gender, and ethnicity predicted intentions to engage in sexual behavior in the future. Relevant knowledge of AIDS was associated with lower intentions to engage in sexual behavior in the future. More frequent substance use, less frequent use of decision-making skills, and being male increased intentions to engage in sexual behavior in the future. Our findings are discussed in terms of their implications for education and prevention of adolescent sexual activity and AIDS-risk reduction.

Acquired Immunodeficiency Syndrome↗

Predictors of cigarette smoking among inner-city minority youth.

Limited information is available concerning the etiology of smoking among minority youth. We examined predictors of smoking among inner-city African-American and Latino seventh graders (N = 757). Enhanced self-reports of cigarette smoking were collected along with data concerning background, social environmental, and individual characteristics hypothesized to promote smoking. Results indicated that friends and peers were the most important social influences in predicting smoking. Several psychological factors, including feelings of hopelessness, low efficacy in life skills (social skills, communication skills, and refusal skills) and low self-esteem seemed related to increased susceptibility to smoking. We discuss implications of our findings for effective prevention programs for minority youth.

Adolescent↗

Attitudes toward AIDS and AIDS education among multi-ethnic parents of school-aged children in New York City.

To explore the attitudes of a multi-ethnic sample (African-American, Caucasian, Latino) of parents, a telephone survey was conducted with 297 parents whose children attend school in New York City (98 African-Americans, 100 Latinos, and 99 Caucasians). The survey interview assessed a wide range of issues related to AIDS and AIDS education. In a series of logistic regressions that controlled for education, we compared each ethnic group (African-Americans, Latinos) with Caucasians as the reference. The majority of parents indicated that they supported AIDS education efforts in the schools, but there was considerable mistrust of the government and health professionals, particularly among the African-American parents. African-American and Latino parents were more likely to perceive AIDS as a threat and believe that AIDS education is more effective for Caucasians. We discuss implications for AIDS prevention and recommend strategies to overcome barriers to AIDS education and prevention in multi-ethnic communities.

Acquired Immunodeficiency Syndrome↗

Spinal cord compression complicating subarachnoid infusion of morphine: case report and laboratory experience.

The intraspinal administration of morphine has been employed increasingly in the management of intractable pain of malignant as well as benign origin. We have encountered a previously unreported clinical complication: spinal cord compression by an inflammatory tissue mass surrounding a subarachnoid infusion catheter administering morphine, leading to paraplegia. The patient was referred to our institution after catheter and pump implantation for chronic, intractable pain associated with pre-existing lumbar arachnoid fibrosis, after multiple myelograms and surgeries. The patient may, therefore, have had an underlying propensity to foreign body reactions. We have encountered a similar phenomenon, however, in a canine laboratory model. The pathological features in both our patient and our laboratory preparation, with inflammatory tissue masses around the tip of the catheter but not around proximal subarachnoid segments, suggest an effect related to infusion, as opposed to infection or the presence of the catheter. We review the pathological features in both settings and the pertinent literature.

Adult↗

Limbus lumbar vertebral fractures in 27 adolescents and adults.

Fractures of the lumbar vertebral limbus involve varying degrees of fragmentation of the peripheral ring apophysis, located at the posterior superior or posterior inferior margins of the mid to lower lumbar vertebrae. Four types, uniquely found in adolescents and young adults, have been described. Type I lesions consist of avulsions of the posterior cortical vertebral rim. Type II fractures are composed of central cortical and cancellous bone fractures. Type III lesions are more lateralized chip fractures. Type IV fractures span the entire length and breadth of the posterior vertebral margin between the end plates. The clinical, neuroradiologic, and surgical management of 27 patients with these four types of lumbar limbus vertebral fractures are reviewed. The data regarding location and type of fracture were critical for planning piecemeal surgical resection with a downbiting curette, tamp, and mallet technique.

Adolescent↗

Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy.

Of 77 patients with supratentorial Grades I and II astrocytoma diagnosed from January 1975 to December 1984, 66 were treated with postoperative radiation therapy. The patients received a tumor dose of 5000 to 5500 cGy in 180 cGy fractions, five fractions per week, over 5.5 to 6 weeks. Overall actuarial survival at 2, 5, and 10 years was 71%, 55%, and 43%, respectively. Progression-free survival at 2, 5, and 10 years was 69%, 50%, and 39%, respectively. Survival for patients receiving postoperative radiation therapy in the range of 4500 to 5900 cGy was 78% and 66% at 2 and 5 years, respectively. Quality of life was determined at two points in time: 1 to 2 years postoperatively, and at last follow-up (2-12 years postoperatively). The occurrence of mental retardation was specifically addressed in long-term survivors, and was observed in 50% of children. Overall, however, 80% of short-term survivors and 67% of long-term survivors were intellectually and physically intact, without major neurologic deficit. Specific prognostic factors were assessed by multivariate analysis. Improved survival was observed with young patients, females, normal preoperative mental status, surgical resection (versus biopsy alone), involvement of only one lobe with tumor, and a history of preoperative seizures. A weighted prognostic factor score derived from these observations permits a clinically useful assessment of risk for individual patients.

Adolescent↗

Far lateral lumbar disc herniations and associated structural abnormalities. An evaluation in 60 patients of the comparative value of CT, MRI, and myelo-CT in diagnosis and management.

The management of 60 patients with far lateral lumbar disc herniations operated on over a 5-year period are presented. These lesions were located superiorly within the neural foramens beneath or distal to the facet joints. The type of surgery performed in 43 of 60 (72%) of these patients was significantly altered by the presence of diffuse and lateral recess stenosis. This was better appreciated on the myelogram and myelo-CT (M-CT) studies than with the noncontrast CT and MRI examinations alone. Myelo-CT findings were particularly valuable in assessing patients who had previous surgical procedures.

Female↗