Mice transgenic for a vasopressin-SV40 hybrid oncogene develop tumors of the endocrine pancreas and the anterior pituitary. A possible model for human multiple endocrine neoplasia type 1.

The authors have used transgenic mice to study the activity of a hybrid oncogene made up of 1.25 kb of 5' upstream sequences, derived from the bovine vasopressin gene, promoting the expression of the large T-antigen coding sequences of the early region of simian virus 40. Rather than promoting tumorigenesis in vasopressinergic cells of the hypothalamus, expression and activity of the hybrid oncogene, and consequent tumor formation, were confined to insulin-producing beta cells of the endocrine pancreas and to cells in the anterior pituitary. These observations suggest that the specificity of vasopressin gene expression normally results from an interaction between several regulatory elements, some of which are absent from the hybrid oncogene. The possible relationship between the endocrine tumor syndrome found in the vasopressin-SV40 transgenic mice and familial human multiple endocrine neoplasia is discussed.     

Allergen sensitization of asthmatic and nonasthmatic schoolchildren in Costa Rica

The prevalence of asthma among schoolchildren in Costa Rica is very high -at the level of 20-30% - and the reason is still unknown. A group of children from our previous epidemiologic study was randomly selected in order to establish the relation between asthma symptoms and allergy sensitization to common allergens. Serum samples from ciiildren with and without asthma were analyzed for the presence of IgE antibodies to 36 different allergens, for the presence of IgE antibodies to a pool of 10 common allergens, and for total serum IgE. The most prevalent IgE antibodies were those to mite, cockroach, dog, and house-dust allergens with MAST pipettes for the serologic measurements. Positive reactions to house dust, mite, cat, and the two molds (Aiternaria and Ciadosporium), and food allergens such as egg white, peanut, and shellfish were significantly more prevalent among the asthmatics than the nonasthmatics. Sensitization was equally prevalent at different ages, but the house-dust, mite, cat, dog, cockroach, Aiternaria, and egg-white allergens had sensitized boys more often than girls (P<0.01). The result of the analysis of IgE antibodies to a pool of 10 common allergens by Phadiatop supported the MAST pipette results, showing allergen sensitization in 57.7% of the asthmatic children and 42.3% in the nonasthmatic group. The concentration of IgE was significantly higher among the asthmatic children (372.2 kU/1) than among the nonasthmatic children (249.1 kU/1) (P < 0.00001). Parasitic infestations were not examined i n this study, but in most of Costa Rica these have largely been eliminated and could not explain the high total IgE levels. Our data indicate that the very high prevalence of bronchial asthma in Costa Rican schoolchildren can be related to sensitization, especially to airborne indoor allergens such as those of mites, cockroaches, and dogs.     

Association of adult height and leg length with fasting plasma cortisol concentrations: Evidence for an effect of normal variation in adrenocortical activity on growth

We have evaluated the relationship between activity of the hypothalamic‐pituitary‐adrenal (HPA) axis and adult height in adults recruited from the UK Hertfordshire Cohort Study. In a sample of 1,354 individuals, we found that height fell by 0.67 cm (95% CI 0.34–1.0) per SD (114 nmol/l) increase in fasting plasma cortisol concentrations. The association was continuous across the range of cortisol concentrations and was independent of the levels of corticosteroid binding globulin. It was of similar magnitude in men and women. In a subsample of the study available data on standing and sitting height was used to estimate trunk and leg length. Fasting plasma cortisol concentrations were found to have a much greater impact on leg length than trunk length. These findings suggest that physiological variations in adrenocortical glucocorticoid secretion in humans affect adult height. They also raise the possibility that the HPA axis may be involved in mediating resource allocation decisions and trade‐offs during development perhaps by limiting physical growth to enable other competing processes. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Familial risk factors to oppositional defiant disorder and conduct disorder: parental psychopathology and maternal parenting.

In a sample of 177 clinic-referred children aged 7-13, an association was found between a diagnosis of conduct disorder (CD) and several aspects of family functioning: maternal parenting (supervision and persistence in discipline) and parental adjustment (paternal antisocial personality disorder and paternal substance abuse). Children with oppositional defiant disorder (ODD) were intermediate to families of children with CD and clinic control children on all variables, but differed from control children only in having a higher rate of paternal substance abuse and paternal antisocial personality disorder (APD). When both parental APD and deviant maternal parenting were entered into 2 x 2 logit-model analyses predicting CD, only parental APD was significantly associated with CD, and no interactions between parental adjustment and maternal parenting were found. The importance of these findings for understanding the etiology of CD and for disentangling correlated risk factors in future studies is discussed.     

Raised dietary n-6 polyunsaturated fatty acid intake increases 2-series prostaglandin production during labour in the ewe

Preterm labour is the major cause of perinatal morbidity and mortality in humans. The incidence is around 10% and the causes are often unknown. Consumption of dietary n -6 polyunsaturated fatty acids (PUFAs) in western societies is increasing. These are metabolized to arachidonic acid, the precursor for 2-series prostaglandins (PGs), major signalling molecules during labour. This study investigated the effect of dietary supplementation with linoleic acid (LA, 18: 2, n -6) on parturition. Ewes were fed a control or LA-supplemented diet from 100 days gestation. Labour was induced using a standardized glucocorticoid challenge (dexamethasone, Dex) to the fetus, starting on day 139. Electromyographic (EMG) activity and fetal and maternal circulating PG concentrations were monitored. One third of LA-fed ewes delivered early (pre-Dex) although basal uterine EMG activity preceding Dex was higher in control ewes  ( P < 0.05)  . A steep increase in EMG activity occurred 18–38 h after the start of Dex infusion. Twice basal EMG activity (defined as established labour) occurred on average 7 h earlier in the LA-supplemented ewes  ( P < 0.05)  . The basal concentrations of maternal and fetal PGFM and fetal PGE₂ were approximately doubled in LA-supplemented ewes before the start of Dex infusion  ( P < 0.01)  . The rise in fetal PGE₂ and maternal oestradiol concentrations post-Dex occurred earlier in the LA-supplemented ewes. All PG measurements remained significantly higher in the LA-supplemented ewes during labour onset. This study suggests that consumption of a high LA diet in late pregnancy can enhance placental PG production and may thus increase the risk of preterm labour.     

Mechanisms of arterial graft failure. 1. Role of cellular proliferation in early healing of PTFE prostheses.

Failure of long-term synthetic arterial bypass grafts has been attributed in part to anastomotic stenosis, but the pathologic basis for this has not been determined. Which cells participate in the formation of the stenosis and the relationship between normal healing and the pathologic development of anastomotic narrowing have not been delineated. In this study we have examined early wound healing in 4-mm polytetrafluorethylene arterial bypass grafts placed in baboons. In this primate model, endothelium and smooth muscle cells (SMCs) derived from the cut ends of adjacent artery form the new intima and migrate together along the luminal surface of the graft at approximately 0.2 mm/day. Both cell types proliferate in association with the growing edge. In addition, both endothelium and SMCs located discretely over anastomoses continue to proliferate despite complete endothelial coverage. Intimal cross-sectional area in this region is always greater than over adjacent graft. Fibroblasts are invariably found in graft matrix and adventitia and do not contribute to formation of intima. It is hypothesized that anastomotic narrowing might be due to chronic endothelial injury and turnover associated with continued SMC proliferation and intimal thickening.     

Haplotypes of the interleukin-4 receptor α chain gene associate with susceptibility to and severity of atopic asthma

BACKGROUND: Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor alpha chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results. OBJECTIVE: We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes. METHODS: IL4R gene haplotypes were analysed, based on the three markers C-3223T, Q551R and I50V, using the expectation-maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians. RESULTS: Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in asthma patients compared with controls (P<0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A subgroup of patients with heterozygous or homozygous state for the T-3223, V50 and R551 alleles, also had lower levels of sIL-4R in their circulation compared with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05) and showed less severe asthma according to lung function test (P<0.05). Analysis of single markers showed the T-3223 IL4R allele to associate with lower serum levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing difficulties, P<0.01). CONCLUSION: Our data suggest that asthmatic patients with low levels of sIL-4 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies.     

The postnatal development of the inferior oblique muscle of the cat. I. Isometric twitch and tetanic properties

The postnatal development of the inferior oblique muscle in the cat has been studied with physiological and histochemical techniques. This paper describes the changes with age in isometric twitch and tetanic response characteristics. The twitch amplitude increased and the twitch contraction time (ct) and half-relaxation time (hrt) decreased almost linearly from birth to adulthood. The relation between the strength of nerve stimulation and twitch ct and hrt changed during development with a threshold slow response appearing at 10 weeks. Twitch responses in cats 6 weeks of age or older were of longer duration than in younger cats, in spite of the longer ct and hrt in young cats. Fusion frequency of the tetanic response reached a constant level in muscles 6 weeks or older. The maximum rate of tension rise remained the same from birth to 6 weeks of age and later increased markedly up to 20 weeks of age. The contracture induced by succinylcholine was the same in muscles of all ages. These data were related to previous findings on the postnatal development of fast and slow muscles and motor units in the hindlimb of the cat. A differentiation of the development of fast and slow eye muscle fibers is suggested. Slow fibres seemed to have completed their maturation at about ten weeks of age, while the development of fast fibre properties continued, probably up to the adult stage.     

Blockade of stimulant-induced preprodynorphin mRNA expression in the striatal matrix by serotonin depletion

Cocaine and methamphetamine (METH) induce preprodynorphin (PPD) mRNA expression in the striatum. Cocaine induces PPD expression in both the patch and matrix compartments of the rostral striatum, whereas METH induces PPD expression in the patch compartment of the rostral striatum. In middle striatum, both stimulants increase PPD expression in the patch and matrix compartments. METH and cocaine treatment also increase extracellular serotonin (5-HT). Several studies have shown that 5-HT receptors are present on striatonigral neurons that express PPD mRNA, and that 5-HT is a positive regulator of striatal neuropeptide expression. The current study examined whether 5-HT plays a role in the patch/matrix expression of PPD mRNA induced by cocaine and METH in striatum. Male Sprague-Dawley rats were treated with p-chloroamphetamine (PCA; 8 mg/kg, i.p), a serotonin neurotoxin, 1 week prior to cocaine (30 mg/kg, i.p) and METH (15 mg/kg, s.c.) treatment. The 80% loss of 5-HT induced by PCA-pretreatment blocked cocaine-induced PPD expression in the rostral matrix compartment. Cocaine- and METH-induced PPD expression in the rostral patch compartment was unaffected by PCA-pretreatment. PCA-pretreatment also decreased both cocaine- and METH-induced PPD expression in the matrix, but not patch of middle striatum. PCA-induced 5-HT depletion did not affect stimulant-induced increases in PPT mRNA expression in the striatum. These data suggest that 5-HT plays a role in stimulant-induced PPD expression in the matrix compartment of rostral and middle striatum. Thus, 5-HT innervation may play a critical role in basal ganglia function.