In vivo measurement of the shear modulus of the human vocal fold: interim results from eight patients

The shear modulus of the vocal fold is an essential parameter required to enhance our understanding of how the vocal fold operates, to develop mathematical models of phonatation, and to provide benchmarks to quantify the effectiveness of surgical procedures. The authors announced the successful deployment of an instrument to measure vocal fold elasticity in vivo last year, and now present the data taken from eight patients in vivo. The shear modulus was measured at the mid-membranous point, in a transverse direction with respect to the axis drawn between the anterior commissure and vocal process. The range of mean shear modulus results is 701–2,225 Pa, with a mean value of 1,371 Pa.     

Predictive testing for Huntington's disease: I. Predictors of uptake in South Wales

In Wales, predictive testing for Huntington's disease (HD) has not been offered proactively to families and uptake of testing is low in comparison to other centres. Little is known of those not requesting testing, particularly those not in direct contact with the genetics service. This study examined differences between a cohort of 22 test applicants and a random group of 32 'non-requesters', drawn from the South Wales HD register. Respondents were interviewed by means of a semi-structured schedule in their own homes. The study groups differed significantly on a number of variables including: knowledge of the availability of testing; perceived attitudes of family members and significant others to testing; length of knowledge and perceived stressfulness of being at risk; and perceived ability to cope with an unfavourable result. Overall, knowledge of testing procedures was poor and at-risk individuals' understanding of genetic terminology was at odds with scientific distinctions. Discussion focuses on the organisational and psychological factors associated with lack of knowledge of the availability of testing and the interpretation of reported coping capacities.     

The effect of estrogens and dietary calcium deficiency on the extracellular matrix of articular cartilage in G?ttingen miniature pigs.

Clinical observations have suggested that estrogens are involved in the pathogenesis of postmenopausal osteoarthritis (OA). However, positive and negative associations between the incidence of OA and serum estrogen concentrations have been reported. In contrast to this, osteoporosis is regarded as a disease with a strong estrogen-dependent component. Moreover, there is an interaction between estrogen and calcium deficiency: calcium supplementation potentiates the effect of estrogen therapy. The present study was designed to investigate how estrogen deficiency affects the articular cartilage depending on calcium supply. The distribution of different types of glycosaminoglycans and collagens can be used as an indicator for extracellular matrix changes induced by estrogen deficiency. Different levels of dietary calcium were therefore fed to intact and ovariectomized G?ttingen miniature pigs for one year before articular cartilage was harvested. The histochemical staining for heavy sulfated glycosaminoglycans in the extracellular matrix of ovariectomized miniature pigs, especially of those fed with a low calcium diet, was stronger in comparison to intact animals. In intact animals type II-collagen was immunodetected in all zones of unmineralized and mineralized articular cartilage, while immunostaining for this protein was negative to weak in the deep radiated fiber zone of ovariectomized minipigs. These results suggest that the synthesis of heavy sulfated glycosaminoglycans and immunohistochemically detectable type II-collagen is possibly influenced by estrogen deficiency. In conclusion, under estrogen deficiency, the extracellular matrix of articular cartilage underwent similar changes to those observed in physiologically aging cartilage where keratan sulfate is increased as a heavy sulfated glycosaminoglycan.     

Prediction of global outcome with acute neuropsychological testing following closed-head injury.

Delaying assessment until emergence from post-traumatic amnesia increases completion rates, but this practice causes variable time delays from the date of injury to testing, which can complicate the interpretation of research findings. In the current study, the performance of 105 head injury survivors on simple tests of language comprehension and attention was used to predict global outcome. It was hypothesized that 1 month performance on these measures would aid in the prediction of Disability Rating Scale (DRS) and Glasgow Outcome Scale (GOS) scores collected at 6 months post injury. Only raw scores on the modified Test of Complex Ideational Material accounted for a significant amount of the variance in DRS scores (4.4%) above that accounted for by age, education, Glasgow Coma Scale score, and pupil response. However, testability at 1 month post injury on all four tests consistently accounted for a larger portion of the variance in DRS scores (10.1-13.2%) and significantly improved prediction of GOS scores. Galveston Orientation and Amnesia Test scores collected at 1 month post injury accounted for substantially less variance in DRS scores (7.7-8.4%). Neuropsychological data, including the testability of patients, collected uniformly at 1 month following injury can contribute to the prediction of global outcome.     

Genetic and phylogeographic structure of populations of<Emphasis Type="Italic"> Pulex simulans</Emphasis> (Siphonaptera) in Peru inferred from two genes (<Emphasis Type="Italic">CytB</Emphasis> and<Emphasis Type="Italic"> CoII</Emphasis>)

In this paper we discuss the potential usefulness of determining the phylogeographic and phylogenetic patterns of a vector for understanding the spread of pathogens or insecticide resistance. We do so using the example of Pulex simulans in Peru. Six populations from six different localities were investigated. Mitochondrial DNA sequences were obtained and branching patterns were inferred using phylogenetic reconstruction methods and nested clade analyses. Ten different haplotypes were discovered. Phylogenetic analysis revealed P. simulans in Peru as a monophyletic group, containing clades that were generally not geographically correlated. The data suggest that P. simulans is not a single genetic entity but rather that this species shows a high degree of intraspecific variation. Restricted gene flow with long distance dispersal coupled with range expansion and long distance colonization are likely to have contributed to the observed patterns of variation.     

Is auditory evoked potential augmenting/reducing affected by acute tryptophan depletion?

Several lines of evidence suggest that the auditory evoked potential (AEP) augmenting/reducing slope may serve as a biological marker of central serotonergic activity. According to Hegerl and Juckel (Biol. Psychiatry, 33, 1993, 173), reduced serotonergic activity is hypothesized to increase the slope of the AEP amplitude stimulus intensity function (ASF-slope). Hints for this hypothesis were investigated by employing the acute tryptophan depletion paradigm in 18 healthy females. A within-subject, placebo controlled double-blind cross over design was used for that purpose. Subjects ingested both a 50 g amino-acid drink with (placebo condition) and without tryptophan (depletion condition). With respect to the N1/P2-slope, test-retest reliability of a 1 week interval ranged between r=0.56 and 0.58 for the pre-ingestion baseline recording sessions. Affect was not altered by tryptophan depletion and not related to the ASF-slope. The comparison between placebo and depletion conditions did not reveal significant alterations of the ASF-slope, neither after 5 nor 6 h post-ingestion. Thus, the results do not support the assumption of the ASF-slope reflecting central serotonergic function.     

An AscI boundary library for the studies of genetic and epigenetic alterations in CpG islands

Knudson's two-hit hypothesis postulates that genetic alterations in both alleles are required for the inactivation of tumor-suppressor genes. Genetic alterations include small or large deletions and mutations. Over the past years, it has become clear that epigenetic alterations such as DNA methylation are additional mechanisms for gene silencing. Restriction Landmark Genomic Scanning (RLGS) is a two-dimensional gel electrophoresis that assesses the methylation status of thousands of CpG islands. RLGS has been applied successfully to scan cancer genomes for aberrant DNA methylation patterns. So far, the majority of this work was done using NotI as the restriction landmark site. Here, we describe the development of RLGS using AscI as the restriction landmark site for genome-wide scans of cancer genomes. The availability of AscI as a restriction landmark for RLGS allows for scanning almost twice as many CpG islands in the human genome compared with using NotI only. We describe the development of an AscI-EcoRV boundary library that supports the cloning of novel methylated genes. Feasibility of this system is shown in three tumor types, medulloblastomas, lung cancers, and head and neck cancers. We report the cloning of 178 AscI RLGS fragments via two methods by use of this library.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.