Genetic and Environmental Influences on Word Recognition and Spelling Deficits as a Function of Age

Previous twin studies have suggested a possible developmental dissociation between genetic influences on word recognition and spelling deficits, wherein genetic influence declined across age for word recognition, and increased for spelling recognition. The present study included two measures of word recognition (timed, untimed) and two measures of spelling (recognition, production) in younger and older twins. The heritability estimates for the two word recognition measures were .65 (timed) and .64 (untimed) in the younger group and .65 and .58 respectively in the older group. For spelling, the corresponding estimates were .57 (recognition) and .51 (production) in the younger group and .65 and .67 in the older group. Although these age group differences were not significant, the pattern of decline in heritability across age for reading and increase for spelling conformed to that predicted by the developmental dissociation hypothesis. However, the tests for an interaction between genetic influences on word recognition and spelling deficits as a function of age were not significant. Edited by Stacey Cherny     

Role of amino acids 261-418 in proteolytic cleavage of the extracellular region of the human thyrotropin receptor.

Previous in vivo cross-linking studies of TSH to the recombinant TSH receptor revealed that the receptor exists at least in part as a single chain glycoprotein of approximately about 100 kilodaltons (kDa), with intramolecular disulfide bonds. TSH also binds to a 54-kDa amino-terminal fragment of the TSH receptor (cleaved up-stream of amino acid residue 317). In the present study in order to better understand the structure of the TSH receptor, we covalently cross-linked radiolabeled TSH to six TSH-LH receptor extracellular region chimeras and the wild-type TSH receptor expressed on Chinese hamster ovary cells in vivo. In these chimeras, different regions of the TSH receptor were substituted with the homologous regions of the LH receptor. When analyzed under nonreducing conditions by polyacrylamide gel electrophoresis, the TSH-cross-linked products were similar to all TSH-LH receptor chimeras and the wild-type receptor. In contrast, differences among the receptors were noted when the TSH-cross-linked products were examined under reducing conditions. With the exception of two chimeras, as noted previously with the wild-type receptor, two TSH-cross-linked products were observed, representing TSH cross-linked to a holoreceptor of about approximately 100 kDa and a fragment of the receptor of about approximately 54 kDa. However, in the two chimeras in which both domains D and E (amino acids 261-418) of the TSH receptor were substituted, only the holoreceptor and not the smaller fragment was detected. Substitution of domains ABC (amino acids 1-260) did not prevent proteolytic cleavage of the TSH receptor. In conclusion, amino acids 261-418 are necessary for proteolytic cleavage of the extracellular region of the human TSH receptor.     

The influence of childhood weight and socioeconomic status on change in adult body mass index in a British national birth cohort

OBJECTIVE: To investigate the effect of childhood weight and childhood socioeconomic status on the pattern of change in body mass index (BMI) between 20 and 43 years. METHODS: A British birth cohort study where the survey members have been followed up regularly since their birth in 1946, with the most recent of 19 follow-ups when the cohort were aged 43 years. BMI was available at 20, 26, 36 and 43 years of age and thus multilevel models for repeated outcome measures were used to model the patterns of change in BMI. RESULTS: The rate of increase in BMI with age was non-linear, with the rate of increase in mean BMI accelerating with increasing age at different rates for men and women. The mean BMI for men was higher than that for women at all ages. Childhood manual social class, defined in terms of father's occupation, and high relative weight at 14 years of age were associated with higher mean BMI across adult life, and these effects increased with age. The effects of childhood relative weight and social class were independent of educational attainment and adult social class. CONCLUSION: The study provides evidence of a long-term effect of childhood social and biological circumstances on BMI. The pathways underlying these relationships may be social or biological, but are not yet fully understood.     

Birth weight, childhood growth and abdominal obesity in adult life.

OBJECTIVE: To examine the relationship of adult abdominal obesity to birth weight, childhood growth and lifetime socioeconomic circumstances. METHODS: A cohort of 3200 men and women with measured waist and hip circumference, height and weight at age 43 who have been followed since their birth in March 1946 in England, Scotland and Wales. Regression models were used to examine mean waist-hip ratio and waist circumference in relation to prospective measures of birth weight, weight relative to height in childhood at ages 4, 7, 11 and 15 and adult body mass index, and to test the independent and interactive nature of the associations and adjust for childhood and adult social class. RESULTS: There was a small inverse effect of birth weight on waist-hip ratio (P=0.037) but not waist circumference in women, after adjustment for current body size. Relative weight at age 7 was inversely related to waist-hip ratio and waist circumference in men (P<0.001 for both) and waist circumference in women (P=0.007) after adjustment for current body size. These relationships were attenuated in men of large body mass index (P<0.01 for interactions between relative weight at 7 y and body mass index in both cases) but were not modified by birth weight. Relative weights at other ages showed similar patterns to those observed at age 7, the effect being weakest at age 4. These findings were independent of lifetime socioeconomic circumstances. CONCLUSION: This study found a small prenatal inverse effect of fetal growth on adult waist-hip ratio due to a reduced hip size. There was also an inverse postnatal effect of childhood growth such that for any given adult body size those who had been lighter in childhood were more at risk of abdominal obesity. These relationships were independent of childhood socioeconomic circumstances and support the idea that insulin resistance may be linked to low weight in childhood.     

Tranilast: a pharmaceutical candidate for reduction of adhesions using a novel approach

Postsurgical adhesion formation has numerous deleterious side effects in a wide variety of surgical settings. Physical barriers used together with laparoscopy were developed in hopes of reducing the tissue trauma seen with open procedures and separating tissues during the critical time of healing to reduce adhesion formation. Despite meticulous techniques by surgeons and the availability of barriers, adhesion formation remains a serious problem, with more than $1 billion spent annually on complications arising from adhesions. Our laboratories have combined a previously marketed drug, Tranilast, with a gel to provide a locally delivered medicated device that can reduce adhesion formation. This article will review the role of Tranilast in the key pathways involved in adhesion formation.     

A STUDY OF THE CHANGES IN VIRULENCE OF THE PNEUMOCOCCUS AT DIFFERENT PERIODS OF GROWTH AND UNDER DIFFERENT CONDITIONS OF CULTIVATION IN MEDIA

It has been possible by rapid transfers alone, not only to maintain the virulence for mice of the pneumococcus in artificial media but also to restore a certain degree of virulence to cultures previously rendered non-virulent by less rapid transfers in the same medium. For these results the presence of enriching fluids such as blood or serum is not required. In addition it has been shown that attenuated cultures, which had been repeatedly demonstrated to be avirulent for mice at the 24 hour period of growth, exhibited marked pathogenicity if injected during, or especially at the commencement of the period of maximum growth when the growth energy may be considered at its height. In these cultures, however, the increase in virulence was usually less than in others transferred repeatedly at frequent intervals. The significance of these results is not necessarily limited to pneumococcus infections. Other lines of investigation are suggested which may possibly help to clarify certain conceptions of the relation which the different activities of the bacterial cell as an agent of infection bear to one another and to the host in various infectious diseases. Although the pneumococcus may offer an especially striking example for purposes of demonstration by experiment, it is not probable that the close relation between the vegetative power or growth energy of the pneumococcus and its pathogenic power is peculiar to this organism. The vegetative power may depend upon many conditions affecting both the host and the bacterial agent of infection. Different species of bacteria may acquire or develop it in different degrees under different conditions. But it must assuredly form the basis not only of the essentially parasitic but also of the more special toxicogenic activities of the bacteria.     

Factor analysis of the items of the state-trait anxiety inventory

The present investigation was designed to determine by factor analysis the nature of the items that comprise the A-State and A-Trait scales of the State-Trait Anxiety Inventory. Three factors were identified. Factor I was defined exclusively by items from the A-State scale. The underlying dimension tapped by the scale was interpreted as state anxiety (how one feels at a particular moment in time); support thus was provided for Spielberger's A-State concept. Items from the A-Trait scale, however, identified two separate factors, neither of which was clearly consonant with Spielberger's concept of A-Trait. Factor II appeared to tap state anxiety according to how the individual generally feels or a typical level of state anxiety as remembered over an indefiniteperiod of time. Factor III was interpreted as a meamre of neuroticism.     

The Efficacy of a Pilot Prevention Program for Children and Caregivers Coping with Economic Strain

Poverty and economic stress are risk factors for child psychopathology; however, primary and secondary control coping can buffer children against the negative effects of these risks. A 4-week (12 h) pilot prevention program aimed at enhancing coping skills and preventing symptoms of psychopathology among children growing up in poverty was evaluated using a multiple baseline design. Participants were 24 children (ages 8–12) and their primary caregivers. Attrition was low and parent-reports of program satisfaction were high. Children’s ability to generate positive coping thoughts and high quality solutions to problems improved from pre- to post-intervention. At the post-intervention measurement, parents’ and children’s involuntary engagement stress responses had declined and parents’ secondary control coping had increased. Children’s internalizing and externalizing symptoms also decreased from pre- to post-intervention, according to parent-reports. Results provide preliminary evidence for the feasibility and efficacy of the intervention.     

Thrombocytosis in childhood: a survey of 94 patients

The introduction of the newer generation of electronic cell counters allows the routine reporting of platelet numbers when the peripheral blood count is requested. In a 12-month period, 100 episodes of marked thrombocytosis (platelet count more than 900 X 10(9)/L) were found among 94 children. These patients were young (median age 9 months). All but one episode of marked thrombocytosis occurred as a phenomenon secondary to a variety of disease states. Infections, especially those involving the central nervous systems were the commonest cause of an elevated platelet count in this series. Malignant diseases alone were rarely associated with thrombocytosis of this magnitude. The elevated platelet count began to decline at a mean of 3 days after diagnosis, and no thrombotic or hemorrhagic complications were encountered. Marked thrombocytosis is a benign, common phenomenon in young children, but specific treatment is not required.     

Steroid-responsive type II anti-factor VIII:C autoantibody in a nonhemophiliac child

Acquired antibodies to factor VIII:C in nonhemophiliac patients are uncommon in adulthood and exceedingly rare in childhood. We report a girl, 9 years of age, with no personal or familial bleeding history who presented with hematuria and bruising 2 weeks after an upper respiratory infection. The activated partial thromboplastin time was 71.9 s (normal, 25-40 s) and did not correct by mixing 1:1 with normal plasma, suggesting the presence of an inhibitor. Factor VIII:C levels were detectable at 0.03 U/ml, but inhibition experiments demonstrated the presence of an inhibitor with an activity of 24 Bethesda U/ml. This inhibitor was localized to the immunoglobulin (IgG) fraction of the patient's plasma. Incubation of the patient's IgG with normal pooled plasma resulted in a 66% decrease in factor VIII:C activity. Unlike the antibodies found in most hemophilia patients, the autoantibody produced by this patient demonstrated type II kinetics and did not inhibit all factor VIII:C activity even at very high concentrations. In addition, the rate of factor VIII:C inactivation by this autoantibody was much slower than that seen with type I inhibitors. The treatment of the patient with prednisone, 2.5 mg/kg/day, resulted in the rapid disappearance of detectable inhibitor and a rise in factor VIII:C levels to 0.70 U/ml. Normal factor VIII:C levels persisted after the discontinuation of steroids. This case is most unusual in that it occurred in a child without any evidence of an underlying autoimmune disorder, and unlike classical hemophiliac factor VIII:C inhibitors, there was a rapid response to steroids.