The uncoupling protein 2 Ala55Val polymorphism is associated with diabetes mellitus: the CARDIA study

BACKGROUND: Uncoupling proteins (UCPs) reduce ATP generation with concomitant increased release of heat. The activities of UCPs have been related to obesity and energy metabolism. METHODS: We investigated the association of the commonly observed UCP2 Ala55Val (V) polymorphism with diabetes mellitus and impaired fasting glucose (IFG) among 3684 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. RESULTS: The V frequency was approximately 45% in blacks and 42% in whites. Those with the Val/Val (VV) genotype had a higher incidence of diabetes than those having the Ala/Ala (AA) genotype (5.8% vs 3.3%; P = 0.02). Similarly, the incidences of diabetes in participants without abdominal obesity were 2.8% and 1.0% (P = 0.03) in the VV and AA groups, and 12.4% and 8.3% (P = 0.15) in participants with abdominal obesity. The incidence of IFG was higher in VV vs AA only in those without abdominal obesity (12.9% vs 9.2%). These trends persisted in minimally and fully adjusted models, and in strata of blacks and whites and men and women. The homeostasis model assessment for insulin resistance was highest in VV in the combined group of those with IFG or untreated diabetes, but not in those with normal fasting glucose. CONCLUSION: The VV genotype of the UCP2 polymorphism was positively related to diabetes. It may involve increased insulin resistance in those with impaired glucose homeostasis.     

Short-term adaptation of auditory receptive fields to dynamic stimuli

Short-term adaptation and recovery from adaptation have a strong impact on the processing of dynamic stimuli. Adaptive effects on neuronal activity have been studied most commonly for changes in first-order statistics of stimuli such as stepwise increments or decrements in stimulus amplitude. However, changes in higher moment statistics, such as the variance of the amplitude distribution in visual stimuli, also can invoke pronounced adaptation behavior. We demonstrate here that neurons in the inferior colliculus (ICC) of the cat show adaptation to dynamic auditory stimuli that differ in the variance of their modulation depth distribution. In addition, it is shown that neurons show adaptation to other higher moment statistics (e.g., kurtosis) of the modulation envelope. The time course of adaptation is specific for the altered stimulus property and the direction of parameter change. The use of dynamic stimuli allows an estimate of the effects of the adaptation on the temporal response properties of the neurons. We demonstrate that temporal receptive fields of neurons undergo change during the course of adaptation. We show that adaptation to variance in the ICC has many similarities to that in the retina and suggest that adaptation to variance is a general property of sensory systems that allows them to effectively deal with a nonstationary environment.     

Attrition, abrasion, corrosion and abfraction revisited: a new perspective on tooth surface lesions

OVERVIEW: The authors propose updated and revised nomenclature, definitions and classification for tooth surface lesions. Their objective is standardization, clarity and clinical utility for the dental practitioner. The article presents a schema of the pathodynamic mechanisms in the formation of tooth surface lesions--three basic physical and chemical mechanisms, their interactions and their dental manifestations. CONCLUSIONS AND CLINICAL IMPLICATIONS: The use of precise definitions will assist the practitioner in determining the etiology of various tooth surface lesions. Understanding the pathodynamic mechanisms and their many possible interactions, as set forth in the schema, will enable the practitioner to make an accurate differential diagnosis and to provide effective prevention and treatment. It also will assist dentists in communicating more effectively with their colleagues as well as with their patients. In addition, the schema helps identify areas in which future research is indicated.     

Selective inhibitors of type I receptor kinase block cellular transforming growth factor-beta signaling

Transforming growth factor (TGFbeta) is a 25-kDa dimeric polypeptide that plays a key role in a variety of physiological processes and disease states. Blocking TGFbeta signaling represents a potentially powerful and conceptually novel approach to the treatment of disorders in which the signaling pathway is constitutively activated, such as cancer, chronic inflammation with fibrosis and select immune disorders. In this paper, we describe the biological properties of a novel series of quinazoline-derived inhibitors of the type I transforming growth factor receptor kinase (TbetaKIs) that bind to the ATP-binding site and keep the kinase in its inactive conformation. These compounds effectively inhibited TGFbeta-induced Smad2 phosphorylation in cultured cells in vitro with an IC(50) between 20 and 300 nM. Moreover, TbetaKIs were able to broadly block TGFbeta-induced reporter gene activation. Finally, TbetaKIs inhibited TGFbeta-mediated growth inhibition of normal murine mammary epithelial cells (NMuMG) and mink lung epithelial cells (Mv1Lu), and TGFbeta-induced epithelial-mesenchymal transdifferentiation (EMT) of NMuMG cells. Thus, these chemical TbetaKIs have the potential to be further developed as anti-cancer and -fibrosis agents. In addition, they represent valuable new tools for dissecting the biochemical mechanisms of TGFbeta signal transduction and understanding the role of TGFbeta signaling pathways in different physiological and disease processes.     

Humor as an additional component of psychological and psychiatric diagnostics in children and adolescents: concept of a humor-diagnostic model

When looking at humor of children and adolescents from a diagnostic point of view, there exist additional diagnostic possibilities other than the usual assessment methods from child and adolescent psychiatry or psychology. Spontaneous humorous behavior in everyday life and a humorous performance during assessment situations of children can provide a useful basis for further diagnostic considerations. From a developmental point of view it is important to notice what kinds of humor a child is already capable of understanding and of performing towards others. Whilst the actual readiness for cheerfulness contains information concerning the emotional state, the more general readiness for being cheerful renders insight into basic parameters of temperament. To what extent a child uses humor either supportively or destructively, contains information about psychodynamic connections, motivational aspects and active coping strategies. Concerning the diagnostic approach, reports of parents as well as humor tests or hypothesizing methods (e.g. humorous drawings) can be used. Central in using humor as a diagnostic assessment device is the knowledge of humor development and of the relations between psychiatric illnesses and humor.     

A liberalized fasting guideline for formula-fed infants does not increase average gastric fluid volume before elective surgery

Recommended preoperative fasting intervals for infant formula vary from 4 to 8 h. We conducted a prospective, randomized, observer-blinded trial of 97 ASA physical status I and II infants scheduled for elective surgery to determine whether average gastric fluid volume (GFV) recovered from infants formula-fasted for 4 h (liberalized fast, Group L) differed from that recovered from infants allowed clear liquids up until 2 h, but fasted 8 h for formula and solids (traditional fast, Group T). In Group L, 31 of 39 subjects followed protocol and ingested formula 4-6 h before surgery. In Group T, 36 of 58 subjects followed protocol, taking clear liquids 2-5 h before the induction of anesthesia. Thirty subjects had prolonged fasts and were included only in a secondary intent-to-treat analysis. Respective mean age (5.7 +/- 2.3 versus 6.4 +/- 2.4 mo; range, 0.7-10.5 mo), weight (7.5 +/- 1.8 versus 7.5 +/- 1.1 kg), and volume of last feed (4.9 +/- 2.2 versus 4.0 +/- 2.3 oz.) did not vary between Groups L and T. GFV (L: 0.19 +/- 0.38 versus T: 0.16 +/- 0.30 mL/kg) and gastric fluid pH (L: 2.5 +/- 0.5 versus T: 2.9 +/- 1.3) did not vary. For all subjects, GFV (mL/kg) increased with age (Spearman correlation coefficient = +0.23, P = 0.03). Infant irritability and hunger and parent satisfaction were similar between groups. We conclude that average GFV after either a 4- to 6-h fast for infant formula or 2-h fast after clear liquids is small and not significantly different between groups. On the basis of these findings, clinicians may consider liberalizing formula feedings to 4 h before surgery in selected infants. IMPLICATIONS: Healthy infants aged < or =10.5 mo may drink formula up to 4 h before surgery without increasing gastric fluid volume compared with infants allowed clear liquids up to 2 h and formula 8 h before surgery.     

Murine pancreatic tumor cell line TD2 bears the characteristic pattern of genetic changes with two independently amplified gene loci

TGFalpha/p53(+/-) transgenic mice represent a genetically engineered mouse model for pancreatic adenocarcinoma. The tumors develop a characteristic pattern of secondary genetic changes. From one of these tumors, the permanent cell line TD2 was established. Here, we describe in detail the genetic changes by molecular-cytogenetic techniques. The original tumor-specific CGH profile has been retained unchanged. The most characteristic aberration pattern bears chromosome 11. Egfr, localized on proximal chromosome 11, is amplified two to three times and leads to an easily identifiable, stable marker chromosome with a large amplification unit, which is present in each metaphase. The wild-type p53 gene on distal chromosome 11 is lost. The p16Ink4a locus on chromosome 4 is hypermethylated. For c-Myc a 15-fold amplification, present in a 1.65 Mb amplification unit, is detected on chromosome 15. Transition between presence in the form of several double minutes, DMs, or a single homogeneously staining region, HSR, was observed for c-Myc. Molecular-cytogenetic analysis of both amplification units show that Egfr amplification and c-Myc amplification represent two alternative modes by which genes get amplified in tumor cells. The expression level of the respective genes was proven by Northern blot analysis. The cell line TD2 represents a valuable in vitro model for pancreatic adenocarcinoma.