Extracellular matrix proteins: a positive feedback loop in lung fibrosis?

Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the development of bleomycin-induced lung fibrosis. We further report in vitro experiments clarifying both the effect of myofibroblast differentiation on this expression and the effect of extracellular elastin on myofibroblast differentiation. Lung fibrosis was induced in female C57Bl/6 mice by bleomycin instillation. Animals were sacrificed at zero to five weeks after fibrosis induction. Collagen synthesized during the week prior to sacrifice was labeled with deuterium. After sacrifice, lung tissue was collected for determination of new collagen formation, microarray analysis, and histology. Human lung fibroblasts were grown on tissue culture plastic or BioFlex culture plates coated with type I collagen or elastin, and stimulated to undergo myofibroblast differentiation by 0-10 ng/ml transforming growth factor (TGF)ß1. mRNA expression was analyzed by quantitative real-time PCR. New collagen formation during bleomycin-induced fibrosis was highly correlated to gene expression of elastin, type V collagen and tenascin C. At the protein level, elastin, type V collagen and tenascin C were highly expressed in fibrotic areas as seen in histological sections of the lung. Type V collagen and tenascin C were transiently increased. Human lung fibroblasts stimulated with TGFß1 strongly increased gene expression of elastin, type V collagen and tenascin C. The extracellular presence of elastin increased gene expression of the myofibroblastic markers α smooth muscle actin and type I collagen. The extracellular matrix composition changes dramatically during the development of lung fibrosis. The increased levels of elastin, type V collagen and tenascin C are probably the result of increased expression by fibroblastic cells; reversely, elastin influences myofibroblast differentiation. This suggests a reciprocal interaction between fibroblasts and the extracellular matrix composition that could enhance the development of lung fibrosis.

Verbal and memory skills in males with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive pediatric disorder that affects both muscle and brain. Children with DMD have mean IQ scores that are about one standard deviation lower than population means, with lower Verbal IQ than Performance IQ scores. For the present study, verbal skills and verbal memory skills were examined in males with DMD with the Clinical Evaluation of Language Fundamentals, 3rd edition, and the California Verbal Learning Test for Children. Performance of 50 males with DMD (age range 6-14 y, mean 9 y 4 mo [SD 2 y 1 mo]) was compared to normative values. Two subsets of the probands were also compared with two comparison groups: unaffected siblings (n=24; DMD group age range 6-12 y, mean 9 y 1 mo [SD 1 y 8 mo]; sibling age range 6-15 y, mean 9 y 11 mo [SD 2 y 4 mo]) and males with cerebral palsy (CP); (n=23; DMD group age range 6-9 y, mean 7 y 8 mo [SD 1 y 2 mo]; CP age range 6-8 y, mean 6 y 8 mo [SD 0 y 8 mo]). Results demonstrated that although males with DMD performed slightly more poorly than normative values, they performed comparably to the controls on most measures. Consistent deficits were observed only on tests requiring immediate repetition for verbal material (Recalling Sentences, and Concepts and Directions). On other language tasks, including tests of understanding and use of grammar, and understanding of semantic relationships, the males with DMD performed well. Moreover, the males with DMD performed well on multiple indices of verbal recall, and there was no evidence of declarative memory deficits. DMD is a single-gene disorder that is selectively associated with decreased verbal span capacity, but not impaired recall.

Poor facial affect recognition among boys with duchenne muscular dystrophy.

Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a matching-to-sample test with four types of visual recognition (Object, Face, Affect, and Situation matching) developed by Lucci and Fein. Within-group analyses on 50 boys with MD found decreased Affect matching relative to the other matching conditions. Between-group comparisons on 20 sibling pairs found the boys with Duchenne performed more poorly only on the Affect-matching condition. Thus, mildly impaired facial affect recognition may be part of the phenotype associated with Duchenne or Becker MD.

Reliability of self-reported contraceptive use and sexual behaviors among adolescent girls.

This study examines two issues relevant to adolescents' self-reported sexual and contraceptive use behaviors: reliability of partner-referent reports versus 3 and 6 month reports, and test-retest reliability of reports completed over a 2 week period. Data are from 196 13 to 18 year old girls recruited into this study while they south reproductive care from health clinics in a metropolitan area. All participants reported having had sexual intercourse during the past 6 months. Twice over a 2 week interval, participants completed the same paper and pencil surveys. The survey presented questions about sexual behavior and contraceptive use using 3 sequential frames of reference: within the past 6 months, within the past 3 months, and by specific sexual partners in the past 6 months. Findings demonstrate that adolescent girls can reliably report sexual behavior and contraceptive use over a 6 month interval. Study findings have implications for future research utilizing adolescents' self-reported sexual and contraceptive use behaviors.

Investigation of Poor Academic Achievement in Children with Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the normal range, generally with lower verbal than performance IQ scores. Prior work has demonstrated selective deficits on tests of verbal span and immediate memory. For the current study, 26 boys with DMD (and normal intellectual function) and their unaffected siblings were evaluated. Paired comparisons demonstrated that the children with DMD had significantly poorer academic achievement scores than their siblings, even though their vocabulary levels and home and educational environments were comparable. Children with DMD also had more behavioral concerns, physical disabilities, and poorer verbal memory spans. Linear regression indicated that behavioral concerns, executive function, and physical disability did not contribute substantially to academic performance, whereas performance on verbal span did. DMD presents with a selective developmental aberration in verbal span that has wide-ranging consequences on learning skills.

Pregnancy feelings among adolescents awaiting pregnancy test results.

OBJECTIVE: The authors surveyed adolescent girls about their feelings regarding pregnancy. METHODS: A survey was administered to 117 13- to 18-year-olds who obtained pregnancy tests at nine clinics in Minneapolis and St. Paul, Minnesota, in 1998. The survey included four measures of pregnancy feelings. The authors used bivariate and multivariate logistic regression analyses to examine the associations of these measures with engagement with school, future expectations, social and environmental characteristics, and perceived partner desire for pregnancy. RESULTS: The four measures of pregnancy feelings were highly correlated (P = 0.0001). Participants reported a range of positive, negative, and ambivalent feelings on all measures. Perceived partner desire for pregnancy, limited future expectations, and lack of school engagement were significantly associated with positive pregnancy feelings for the four measures. CONCLUSIONS: Successful adolescent pregnancy prevention interventions may include the involvement of partners and key adults as well as strategies to enhance the educational or employment aspirations of girls and adolescents.

Prevalence of home pregnancy testing among adolescents.

OBJECTIVES: This study estimated the prevalence of home pregnancy testing among adolescents. METHODS: A survey was administered in 11 urban clinics to 600 females aged 13 to 19 years. RESULTS: The prevalence of home pregnancy test use was 34% among 474 sexually experienced youths; 77% of the users had received at least 1 negative pregnancy test result, and 48% took no further action for confirmation. Compared with those who had never used such tests, users were older, younger at sexual debut, less likely to consistently use effective birth control, and more likely to have ever been pregnant. CONCLUSIONS: Health care clinics are important sources for pregnancy prevention, but clinics may have limited opportunity to intervene with some youths who use home pregnancy tests.

Partnerships for comprehensive school health: collaboration among colleges/universities, state-level organizations, and local school districts.

A qualitative survey on the collaborative experiences of colleges and universities, state-level organizations, and school districts related to comprehensive school health programs in 12 states found four primary collaborative outcomes: training, consultation, research, and networking. Five common dimensions of collaboration also were identified: interpersonal and organizational interactions, level of awareness and understanding of comprehensive school health programs, organizational priorities and reward systems, political forces, and availability and sharing of resources. The potential for such linkages to advance comprehensive school health programs remains largely untapped. Recommendations for developing such collaborations are presented.

Crossover isomer bias is the primary sequence-dependent property of immobilized Holliday junctions.

Recombination of genes is essential to the evolution of genetic diversity, the segregation of chromosomes during cell division, and certain DNA repair processes. The Holliday junction, a four-arm, four-strand branched DNA crossover structure, is formed as a transient intermediate during genetic recombination and repair processes in the cell. The recognition and subsequent resolution of Holliday junctions into parental or recombined products appear to be critically dependent on their three-dimensional structure. Complementary NMR and time-resolved fluorescence resonance energy transfer experiments on immobilized four-arm DNA junctions reported here indicate that the Holliday junction cannot be viewed as a static structure but rather as an equilibrium mixture of two conformational isomers. Furthermore, the distribution between the two possible crossover isomers was found to depend on the sequence in a manner that was not anticipated on the basis of previous low-resolution experiments.

Physical activity and mortality in postmenopausal women.

OBJECTIVE: To evaluate the association between physical activity and all case mortality in postmenopausal women. DESIGN: Prospective cohort study with 7 years of follow-up through December 31, 1992. SETTING AND PARTICIPANTS: Subjects were 40417 postmenopausal Iowa women, aged 55 to 69 years at baseline in 1986. Physical activity was assessed by mailed questionnaire. MAIN OUTCOME MEASURE: All-cause mortality (n=2260). RESULTS: After adjustment for potential confounders and excluding women who reported having cancer or heart disease and those who died in the first 3 years of follow-up, women who reported regular physical activity were at significantly reduced risk of death during follow-up compared with women who did not (relative risk [RR], 0.77; 95% confidence interval [CI], 0.66-0.90). Increasing frequency of moderate physical activity was associated with reduced risk of death during follow-up (from rarely or never engaging in activity to activity at least 4 times per week, RRs, 1.0 [referent], 0.76, 0.70, and 0.62; P value for trend<.001). A similar pattern was seen for vigorous physical activity (corresponding RRs, 1.0, 0.89, 0.74, and 0.57; Pvalue for trend=.06). Reduced risks of death with increased physical activity were evident for cardiovascular diseases (n=729) and respiratory illnesses (n=147). Women who engaged only in moderate but not vigorous physical activity also benefited, with moderate activity as infrequently as once per week demonstrating a reduced mortality risk of 0.78 (95% CI, 0.64-0.96). CONCLUSIONS: These results demonstrate a graded, inverse association between physical activity and all-cause mortality in postmenopausal women. These findings strengthen the confidence that population recommendations to engage in regular physical activity are applicable to postmenopausal women.

Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study.

The association between dietary antioxidant vitamin intake and the risk of breast cancer was examined in a prospective study of 34,387 postmenopausal women in Iowa. Intakes of vitamins A, C, and E and of retinol and carotenoids were assessed in 1986 by mailed semiquantitative food frequency questionnaire. Through December 31, 1992, 879 incident breast cancer cases occurred in this cohort. There was little suggestion that breast cancer risk was associated with differences in intake of these vitamins. For example, from the lowest to highest total vitamin A intake categorized by quintiles, the age-adjusted relative risks of breast cancer were 1.0, 0.95, 1.17, 1.20, and 0.90 (p trend = 0.92). Similarly unremarkable relative risk patterns were seen for the intakes of vitamins C and E and of retinol and carotenoids. These findings were not altered after adjustment for breast cancer risk factors or in analyses confined to women who reported no supplemental vitamin intake. Exclusion of cases that occurred in the first 2 years of follow-up, under the assumption that women may have increased intake of these vitamins in response to preclinical symptoms of breast cancer, did not suggest an inverse association of these vitamins with the risk of breast cancer. Women who reported consuming at least 500 mg/day of supplemental vitamin C had a relative risk of breast cancer of 0.79 compared with women who did not take supplemental vitamin C, and women who reported consuming more than 10,000 IU/day of vitamin A had a corresponding relative risk of 0.73. However, these relative risks were not statistically significant. These results provide little evidence that intake of these vitamins is associated with breast cancer risk.

The relative effectiveness of three techniques to induce the trophotropic response.

The purpose of this study was to examine the relative effectiveness of electromyographic biofeedback training (EMG BFT), meditation, and progressive muscle relaxation (PMR) in eliciting a relaxation or trophotropic response as measured by frontalis muscle tension, heart rate, electrodermal response, respiration rate, and skin temperature. Fifty-four college students were randomly assigned to one of five groups: (1) control, (2) placebo control, (3) EMG BFT, (4) meditation, (5) PMR. After baseline measures were obtained subjects were trained in 10 30-minute training sessions and posttested. Comparisons by ANOVAs indicated there was a significant decrease in muscle tension in the EMG BFT and meditation groups and significant decreases in respiration rate in the meditation and PMR groups. No other changes were attributed to treatment.