Characterization of a family of gamma-ray-induced CHO mutants demonstrates that the ldlA locus is diploid and encodes the low-density lipoprotein receptor.

The ldlA locus is one of four Chinese hamster ovary (CHO) cell loci which are known to be required for the synthesis of functional low-density lipoprotein (LDL) receptors. Previous studies have suggested that the ldlA locus is diploid and encodes the LDL receptor. To confirm this assignment, we have isolated a partial genomic clone of the Chinese hamster LDL receptor gene and used this and other nucleic acid and antibody probes to study a family of ldlA mutants isolated after gamma-irradiation. Our analysis suggests that there are two LDL receptor alleles in wild-type CHO cells. Each of the three mutants isolated after gamma-irradiation had detectable deletions affecting one of the two LDL receptor alleles. One of the mutants also had a disruption of the remaining allele, resulting in the synthesis of an abnormal receptor precursor which was not subject to Golgi-associated posttranslational glycoprotein processing. The correlation of changes in the expression, structure, and function of LDL receptors with deletions in the LDL receptor genes in these mutants directly demonstrated that the ldlA locus in CHO cells is diploid and encodes the LDL receptor. In addition, our analysis suggests that CHO cells in culture may contain a partial LDL receptor pseudogene.

DNA-mediated transfer of a human gene required for low-density lipoprotein receptor expression and for multiple Golgi processing pathways.

Transfection of a hamster cell mutant with human DNA corrected both the low-density lipoprotein receptor-deficient phenotype and the multiple glycosylation defects of the cells. Independently transfected colonies contained a small set of common human DNA fragments. These fragments may correspond to the human analog of a single gene required for several different Golgi processing pathways.

Serious injuries and deaths of adolescent girls resulting from interpersonal violence: characteristics and trends from the United States, 1989-1998.

BACKGROUND: Little published data are available concerning the death and disability of adolescent girls resulting from interpersonal violence (adolescents are defined as those aged 12-18 years in this study). OBJECTIVES: To determine whether there were sex differences in (a) the characteristics of those who were injured or died, (b) injury severity and outcomes, and (c) injury mechanism; and to describe time trends in these differences. DESIGN: Analysis of data concerning serious injuries due to assaults, recorded in the National Pediatric Trauma Registry (from January 1, 1989, through December 31, 1998), and homicides, recorded in the Web-Based Injury Statistics and Query Reporting System database (from January 1, 1990, through December 31, 1997). SETTING: Patient data from participating pediatric trauma centers (National Pediatric Trauma Registry) in 45 states and national death certificate data (Web-Based Injury Statistics and Query Reporting System). PATIENTS: Six hundred twelve adolescent girls who were seriously injured because of an assault were compared with 2656 adolescent boys who were seriously injured because of an assault. Three thousand four hundred eighty-seven adolescent girls who died due to a homicide were compared with 17 292 adolescent boys who died due to a homicide. RESULTS: Assaulted adolescent girls were more likely to have preexisting cognitive or psychosocial impairments than were adolescent boys (odds ratio, 1.68; 95% confidence interval, 1.12-2.51). Adolescent girls trended toward more injury-related impairments at discharge from the hospital (odds ratio, 1.16; 95% confidence interval, 0.92-1.47). Adolescent girls were more likely to have been stabbed, and less likely to have been shot. Also, adolescent girls were more likely to have been injured at a home or a residence. Compared with all National Pediatric Trauma Registry admissions, assaults declined at the same rate for adolescent girls and boys. The proportion resulting from penetrating trauma declined more slowly for adolescent girls. CONCLUSIONS: Interpersonal violence causes considerable morbidity and mortality for young women. Research and interventions should be developed to respond to adolescent girls who experience interpersonal violence.

Short-term effectiveness of anticipatory guidance to reduce early childhood risks for subsequent violence.

OBJECTIVE: To determine whether newly developed anticipatory guidance materials designed to teach the use of time-outs and the importance of reductions in childhood television viewing would be recalled by parents and if their use would result in changes in self-reported parental behavior. SUBJECTS AND SETTING: A total of 559 parents of children aged 14 months to 6 years recruited at the time of routine child health maintenance visits at 2 managed care pediatric departments in eastern Massachusetts. METHODS: In-person parent interviews were conducted in the waiting room prior to office visits, with follow-up telephone calls 2 to 3 weeks after the visit. Two groups of families were enrolled: a control group who received usual anticipatory guidance and an intervention group who received written materials. Intervention group providers were trained to include study topics during the office visit and to introduce the written materials. RESULTS: Provider training and the provision of written materials increased the parents' specific recall of anticipatory guidance of at least 2 to 3 weeks following the office visit. This effect was specific to the areas of intervention and did not carry over to other commonly used topics of anticipatory guidance. Among parents who had never used a time-out prior to the office visit, there was a significant increase in the use of time-outs. Parents who received anticipatory guidance regarding the link between exposure to television violence and subsequent violence in children were somewhat more likely to report reductions in weekend television viewing than were parents in the control group, although this change was not statistically significant. CONCLUSIONS: Certain parenting behaviors have been associated with subsequent violence. Brief, inexpensive anticipatory guidance in relevant areas, provided in the context of routine health supervision visits, appears to result in favorable short-term changes in parenting practices.

Family violence: an overview.

This article reviews the definitions and epidemiology of the several forms of interpersonal violence in family and intimate relationships. Interpersonal violence includes both fatal and nonfatal violence where physical force, or other means, is used by one person with the intent of causing harm, injury, or death: family violence includes child maltreatment, adult intimate-partner violence, and elder mistreatment; abuse refers to a pattern of behaviors organized around the international use of power by one person to control another; and child maltreatment involves the abrogation of adult responsibilities for the care and protection of children, and includes child abuse, child sexual abuse, and child neglect. Violence is a major public health problem in the United States. Half of assault and homicide victims are related to or acquainted with their assailants, as are two-thirds of rape victims. Children and adolescents are at particular risk of violence. The study of interpersonal violence is a complex and evolving held, and is increasingly a part of training and medical practice in academic settings.

Interpersonal violence and the education of physicians.

Physicians in every field of practice can expect to be called upon to care for patients whose lives have been affected by interpersonal violence. Although the medical profession has begun to acknowledge the appropriate role of physicians in screening, diagnosis, and treatment of interpersonal violence, these areas have not been fully addressed in the curricula of most medical schools. Competencies in the understanding of violence and its treatment are proposed for medical students, residents, and practicing physicians. By the time of graduation, all medical students should be able to demonstrate appropriate attitudes, core knowledge, and basic skills in assessment and intervention of patients at risk from or experiencing violence. During postgraduate training, residents should amass specialized knowledge and skill concerning the spectrum of injuries and illnesses they may encounter in clinical practice. Faculty development efforts should address the advancement of faculty who are well trained in a scholarly approach to teaching and research in this field. This paper describes methods by which educational efforts in interpersonal violence can be introduced into medical education. Proposed goals and objectives for curriculum development in schools of medicine, along with an implementation plan, are offered.

Violence: A preventable cause of head injury in children.

Violence is one of the most important and preventable causes of head injury in children. This review discusses the epidemiology of youth violence from previously published reports and from new information obtained from the National Pediatric Trauma Registry. Violence prevention is considered in two categories: primary prevention aimed at the general population, and secondary prevention strategies focused on injured children and adolescents. Rehabilitation professionals have substantial roles to play in both primary and secondary prevention of youth violence.

A statistical test for comparing several nucleotide sequences.

A statistical test useful for the simultaneous comparison of nucleotide sequences is presented. A likelihood ratio test is derived, examples demonstrated, and tables of critical values are provided.

Expression and regulation of human low-density lipoprotein receptors in Chinese hamster ovary cells.

Low-density lipoprotein (LDL), the major cholesterol transport component of human plasma, delivers cholesterol to mammalian cells via the LDL pathway of receptor-mediated endocytosis. LDL receptor activity and cholesterol biosynthesis are coordinately regulated by cholesterol-mediated feedback suppression. We have developed methods for the isolation of mutant and revertant (M.K., unpublished data) Chinese hamster ovary (CHO) cells having alterations in cholesterol biosynthesis and in the receptor-mediated endocytosis of LDL. The defective locus of one LDL receptor-negative CHO mutant (clone 7a-1) is apparently the structural gene for the LDL receptor (D. Kingsley, M. Segal and M.K., unpublished data). Here we have transfected 7a-1 cells with human DNA and selected colonies which synthesize functional human LDL receptors whose expression is regulated normally. This selection may prove useful for cloning genes required for the receptor-mediated endocytosis of LDL and other ligands and thus for elucidating the molecular defects responsible for familial hypercholesterolaemia, one of the most common genetic diseases in humans.

Comparing pediatric intentional injury surveillance data with data from publicly available sources: consequences for a public health response to violence.

OBJECTIVE: A hospital based intentional injury surveillance system for youth (aged 3-18) was compared with other publicly available sources of information on youth violence. The comparison addressed whether locally conducted surveillance provides data that are sufficiently more complete, detailed, and timely that clinicians and public health practitioners interested in youth violence prevention would find surveillance worth conducting. SETTING: The Boston Emergency Department Surveillance (BEDS) project was conducted at Boston Medical Center and the Children's Hospital, Boston. METHOD: MEDLINE and other databases were searched for data sources that report separate data for youth and data on intentional injury. Sources that met these criteria (one national and three local) were then compared with BEDS data. Comparisons were made in the following categories: age, gender, victim-offender relationship, injury circumstance, geographic location, weapon rates, and violent injury rates. RESULTS: Of 14 sources dealing with violence, only four met inclusion criteria. Each source provided useful breakdowns for age and gender; however, only the BEDS data were able to demonstrate that 32.6% of intentional injuries occurred among youth aged 12 and under. Comparison data sources provided less detail regarding the victim-offender relationship, injury circumstance, and weapon use. Comparison of violent injury rates showed the difficulties for practitioners estimating intentional injury from sources based on arrest data, crime victim data, or weapon related injury. CONCLUSIONS: Comparison suggests that surveillance is more complete, detailed, and timely than publicly available sources of data. Clinicians and public health practitioners should consider developing similar systems.