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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 19 recordsLinked to original sources
PubMed2006

Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia.

The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.

5' Untranslated Regions↗
PubMed2006

The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children.

BACKGROUND: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. METHODS: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. RESULTS: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. DISCUSSION: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.

Alleles↗
PubMed2006

Observation of Psi(3770)-->gammachi(c1)-->gammagammaJ/Psi.

From e(+)e(-) collision data acquired with the CLEO detector at the Cornell Electron Storage Ring, we observe the non-DD(_) decay Psi(3770))-->gammachi(c1) with a statistical significance of 6.6 standard deviations, using the two-photon cascades to J/Psi and J/Psi-->l(+)l(-). We determine sigma(e(=)e(-)-->Psi(3770))xBeta(Psi(3770)-->gammachi(c1))=(18.0 +/- 3.3 +/- 2.5) pb and branching fraction Beta(Psi(3770)-->gammachi(c1)=(2.8 +/- 0.5+/-0.4) x 10(-3). We set 90% C.L. upper limits for the transition to chi(c2) (chi(c0)): sigma x Beta<5.7 pb (<282 pb) and Beta<0.9 x 10(-3) (<44 x 10(-3)). We also determine Gamma(Psi(3770)gammachi(c1))/Gamma(Psi(3770)-->pi(+)pi(-)J/Psi)=1.5 +/- 0.3 +/- 0.3 (>1.0 at 90% C.L.), which bears upon the interpretation of X(3872).

Journal Article↗
PubMed2006

Observation of psi(3770) --> pi pi J/psi and measurement of Gamma ee[psi(2S)].

We observe signals for the decays psi(3770) --> XJ/psi from data acquired with the CLEO detector operating at the CESR e+ e- collider with square root of s = 3773 MeV. We measure the following branching fractions Beta(psi(3770) --> XJ/psi and significances: (189 +/- 20 +/- 20) x 10(-5) (11.6sigma) for X = pi+ pi-, (80 +/- 25 +/- 16) x 10(-5) (3.4sigma) for X = pi0 pi0, and (87 +/- 33 +/- 22) x 10(-5) (3.5sigma) for X = eta, where the errors are statistical and systematic, respectively. The radiative return process e+ e- --> gamma psi(2S) populates the same event sample and is used to measure Gamma ee[psi(2S)] = (2.54 +/- 0.03 +/- 0.11) keV.

Journal Article↗
PubMed2006

Observation of Bs production at the Y(5S) resonance.

Using the CLEO detector at the Cornell Electron Storage Ring, we have observed the Bs meson in e+e- annihilation at the Y(5S) resonance. We find 14 candidates consistent with Bs decays into final states with a J/psi or a Ds(*)- . The probability that we have observed a background fluctuation is less than 8 x 10(-10) . We have established that at the energy of the Y(5S) resonance Bs production proceeds predominantly through the creation of Bs*Bs* pairs. We find sigma(e+e- --> Bs*Bs*) = [0.11(-0.03))(+0.04)(stat) +/- 0.02(syst)]nb , and set the following limits: sigma(e+e- --> BsBs)/ sigma(e+ e- --> Bs*Bs*) <0.16 and [sigma(e+e- --> BsBs*) + sigma(e+e- --> Bs*Bs)]/sigma(e+e- -->Bs*Bs*) < 0.16 (90% C.L.). The mass of the Bs* meson is measured to be M(Bs*) = [5.414+/- 0.001(stat) +/- 0.003(syst)] GeV/c2 .

Journal Article↗
PubMed2006

Putting the computation back into computational modeling.

Many different varieties of modeling coexist in theoretical neuroscience. Here, we consider the positive and negative implications, for theories of schizophrenia, of a crucial distinction between computational and mathematical modeling.

Brain↗
PubMed2006

Is there peripheral or ovarian insulin action alteration in broiler breeder hens fed ad libitum?

We investigated whether a change in peripheral glucose homeostasis, a local change in the insulin-related ovarian regulatory system, or both occurred in ad libitum-fed broiler breeder hens compared with feed-restricted counterparts. Feed-restricted (R, from 5 to 16 wk of age) and ad libitum-fed (A) hens from a standard commercial line (S) and an experimental dwarf genotype (E) were studied. Basal and stimulated plasma insulin and glucose concentrations were measured during the prebreeding and laying periods. In the basal state (after 16 h fasting) plasma glucose concentrations were significantly lower in SA chickens (-5% at 17 wk, -7.5% at 32 wk) compared with EA, SR, and ER chickens, with no difference in plasma insulin concentrations (n = 16). In 17-wk-old SA birds, 30 min after oral glucose loading, plasma glucose concentrations increased significantly compared with the basal state and were also significantly lower as compared with SR but did not differ significantly from EA and ER. Plasma insulin concentrations did not differ significantly between genotypes or regimens (n = 16). A potential modification of intracellular mediators involved in the regulation of cell growth and survival in small follicles that were overrecruited in SA compared with SR was also investigated in SA and SR hens at 32 wk. There was no effect of food restriction in phospho-Akt, Akt, phospho-ERK, and phospho-S6 in the small white ovarian follicles (n = 6) in the basal state and after 30 min of refeeding. In conclusion, the present study does not demonstrate any evidence of glucose intolerance during the prebreeding period, specific change in the ovarian small follicle insulin signalling pathway, or both, in laying broiler breeders fed ad libitum compared with feed-restricted hens.

Animals↗
PubMed2006

Effects of genotype and feed allowance on plasma luteinizing hormones, follicle-stimulating hormones, progesterone, estradiol levels, follicle differentiation, and egg production rates of broiler breeder hens.

The aim of this study was to compare and relate plasma hormone levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), estradiol (E2), and the in vitro P4 production capacity of the largest yellow (F1) follicle granulosa cells with the laying performance of 2 genotypes (a standard S line and a dwarf cross-experimental E line) maintained under ad libitum (SA, EA) or restricted (SR, ER) feeding regimens. Age-related hormone changes were determined from 4 to 50 wk, hormone changes during the ovulatory cycle were determined during lay, and changes in follicle granulosa cell P4-producing capacity in response to LH with or without growth factors were measured in vitro at different ages. The mean laying rate was similar for SR, EA, and ER but were lower for the SA. Plasma LH and FSH concentrations increased with age in all groups and peaked at puberty. Restricted feeding delayed puberty in both genotypes. Concentrations of E2 and P4 increased after puberty in all groups but delayed in restricted hens. Plasma levels of LH, FSH, P4, and E2 before and after puberty were not correlated with egg-laying performance, but peak E2 levels were. Luteinizing hormone and P4 concentrations during the ovulatory cycle showed differences that may be associated with the different laying performances of the 2 genotypes under ad libitum and restricted feeding. The increase in plasma LH concentration (from basal) during the preovulatory surge was higher in the SR than in the SA but was similar for EA, ER, and SA. The increase in P4 was also higher in SR than in the SA with no difference between EA and ER. In vitro P4 production by granulosa cells in response to LH with insulin-like growth factors, and bone morphogenetic protein-7 was different among the SA, SR, EA, and ER; the EA, SR, and ER had greater responses, and the SA had less response. The presence of insulin-like growth factors and bone morphogenetic protein-7 enhanced LH effects depending on the feeding regimen and age of hen. This finding suggests that differences in laying performances among genotypes fed at different nutritional levels may be partly due to differences in processes associated with follicular maturation modulated by gonadotropins and growth factors. It is concluded that the age at puberty is determined mainly by feed allowance, irrespective of genotype, and that differences in laying performance may be due to a combination of factors that include changes in the levels of gonadotropins or ovarian hormones and growth factors, BW, and the condition of the different genotypes under different feeding allowances.

Aging↗
PubMed2006

A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury.

Collagen synthesis inhibition potentially can reduce adhesion formation after tendon injury but also may affect cutaneous wound healing. We hypothesized that a novel orally administered collagen synthesis inhibitor (CPHI-I) would substantially reduce flexor tendon adhesions after injury, without any clinically important effect on cutaneous wound healing. The experiments were performed in a rat model with an in-continuity crush injury model in the rat hindfoot flexor tendon to provoke adhesion formation. Assays of dermal collagen production and the rate of healing of an excised wound were performed to assess cutaneous wound healing. Animals in the treatment groups received CPHI-I for 1, 2, or 6 weeks and were assessed at either 2 or 6 weeks. The work of flexion in the injured digit was reduced in the CPHI-I-treated animals compared with control animals, (0.188 J versus 0.0307 J at 2 weeks, and 0.0231 J versus 0.0331 J at 6 weeks) The cutaneous wound healing rate was similar in all animals, but dermal collagen synthesis was reduced in the treated animals. The CPHI-I seems to reduce tendon adhesion, and although collagen synthesis was reduced in cutaneous wounds, CPHI-I did not retard wound healing.

Administration, Oral↗
PubMed2006

Consequences of youth tobacco use: a review of prospective behavioural studies.

BACKGROUND: Cigarette smoking represents a significant health problem and tobacco has been identified as causing more preventable diseases and premature deaths than any other drug. Although health consequences from smoking have been documented, there has been a surprising lack of research into behavioural consequences. AIMS: To review what is known of the long-term relationship between patterns of tobacco use prior to age 18 years and behavioural consequences in adulthood. METHOD: A literature search of electronic abstraction services from 1980 to September 2005 was conducted. To be included in the review, studies had to have large, representative samples, be longitudinal studies with baseline age under 18 years and follow-up age 18 years or older and clarify effects due to attrition, leaving 16 articles that met the inclusion criteria. Two reviewers evaluated each paper. FINDINGS: Adolescent tobacco use predicts a range of early adult social and health problems. Surprisingly few studies met the inclusion criteria. The limited evidence available suggests that adolescent tobacco smoking increases the likelihood of early adult tobacco use and the initiation of alcohol use or the development of alcohol-related problems. The link between adolescent tobacco use and subsequent cannabis use was not resolved convincingly from the studies summarized. The effects of tobacco use on later illicit drug use tended to fall away when adjusting for underlying risk factors. Existing studies of the effects of tobacco use on later mental health have many limitations. Nevertheless, a finding that youth tobacco use may predict subsequent mental health problems deserves further investigation. The possible effects of tobacco use on academic/social problems and sleep problems also warrant further investigation. CONCLUSION: This review highlights links between youth tobacco use and subsequent behavioural and mental health problems. It provides health care professionals with evidence of the possible harmful effects of youth tobacco smoking on later social, emotional, and behavioural well-being.

Adolescent↗
PubMed2006

Motor, visual and egocentric transformations in children with Developmental Coordination Disorder.

AIM: This study aimed to test the internal modelling deficit (IMD) hypothesis using the mental rotation paradigm. BACKGROUND: According to the IMD hypothesis, children with Developmental Coordination Disorder (DCD) have an impaired ability to internally represent action. Thirty-six children (18 DCD) completed four tasks: two versions of a single-hand rotation task (with and without explicit imagery instructions), a whole-body imagery task and an alphanumeric rotation task. RESULTS: There was partial support for the hypothesis that children with DCD would display an atypical pattern of performance on the hand rotation task, requiring implicit use of motor imagery. Overall, there were no significant differences between the DCD and control groups when the hand task was completed without explicit instructions, on either response time or accuracy. However, when imagery instructions were introduced, the controls were significantly more accurate than the DCD group, indicating that children with DCD were unable to benefit from explicit cuing. As predicted, the controls were also significantly more accurate than the DCD group on the whole-body task, with the accuracy of the DCD group barely rising above chance. Finally, and as expected, there was no difference between the groups on the alphanumeric task, a measure of visual (or object-related) imagery. CONCLUSIONS: The inability of the DCD group to utilize specific motor imagery instructions and to perform egocentric transformations lends some support to the IMD hypothesis. Future work needs to address the question of whether the IMD itself is subgroup-specific.

Analysis of Variance↗
PubMed2006

Dermatological manifestations of Down's syndrome.

Down's syndrome (DS) is associated with rare dermatological disorders and increased frequency of some common dermatoses. Owing to advances in medical care and changes in attitude, the median age of death in this population has increased to 49 years, and the life expectancy of a 1-year-old person with DS today is more than 60 years and is likely to improve. With the increase in the number of individuals with DS in the population and an increased life span, dermatologists are more likely to encounter the wide spectrum of dermatological disorders that occurs in these patients. Furthermore, new reports of possible associations are frequent in the literature. The purpose of this article is to discuss the various dermatological conditions that affect DS individuals. A brief overview is given of the new information on genetics and the immunology of DS. We also discuss the molecular mechanisms of premature ageing, to which DS individuals are prone. We review the literature and discuss the known dermatological manifestations, concentrating on recent reports.

Adolescent↗
PubMed2006

Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients.

Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3-6 were classified as having advanced fibrosis (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of > or = 2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80.

Adolescent↗
PubMed2006

Effects of altered nitric oxide availability on rat muscle microvascular oxygenation during contractions.

AIM: To explore the role of nitric oxide (NO) in controlling microvascular O2 pressure (P(O2)mv) at rest and during contractions (1 Hz). We hypothesized that at the onset of contractions sodium nitroprusside (SNP) would raise P(O2)mv and slow the kinetics of P(O2)mv change whereas l-nitro arginine methyl ester (L-NAME) would decrease P(O2)mv and speed its kinetics. METHODS: We superfused the spinotrapezius muscle of female Sprague-Dawley rats (n = 7, body mass = 298 +/- 10 g) with SNP (300 microM) and L-NAME (1.5 mm) and measured P(O2)mv (phosphorescence quenching) during contractions. RESULTS: SNP decreased mean arterial pressure (92 +/- 5 mmHg) below that of control (CON, 124 +/- 4 mmHg) and L-NAME (120 +/- 4 mmHg) conditions. SNP did not raise P(O2)mv at rest but it did elevate the P(O2)mv-to-MAP ratio (50% increase, P < 0.05) and slow the kinetics by lengthening the time-delay (TD, 14.0 +/- 5.0 s) and time constant (tau, 24.0 +/- 10.0 s) of the response compared with CON (TD, 8.4 +/- 3.3 s; tau, 16.0 +/- 4.5 s, P < 0.05 vs. SNP). L-NAME decreased P(O2)mv at rest and tended to speed tau (10.1 +/- 3.8 s, P = 0.1), while TD (8.1 +/- 1.0 s) was not significantly different. L-NAME also caused P(O2)mv to fall transiently below steady-state contracting values. CONCLUSIONS: These results indicate that NO availability can significantly affect P(O2)mv at rest and during contractions and suggests that P(O2)mv derangements in ageing and chronic disease conditions may potentially result from impairments in NO availability.

Animals↗
PubMed2006

Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide availability.

AIM: To test the hypothesis that diminished vascular nitric oxide availability might explain the inability of individuals with chronic heart failure (CHF) to maintain the microvascular PO(2)'s (PO(2mv) proportional, variant O(2) delivery-to-uptake ratio) seen in healthy animals. METHODS: We superfused sodium nitroprusside (SNP; 300 microm), Krebs-Henseleit (control, CON) and L-nitro arginine methyl ester (L-NAME; 1.5 mM) onto the spinotrapezius muscle and measured PO(2mv) by phosphorescence quenching in female Sprague-Dawley rats (n = 26) at rest and during twitch contractions (1 Hz). Seven rats served as controls (Sham) while CHF was induced by myocardial infarction. CHF rats were grouped as moderate (MOD; n = 15) and severe CHF (SEV; n = 4) according to morphological data and baseline PO(2mv). RESULTS: In contrast to Sham and MOD, L-NAME did not affect the PO(2mv) response (dynamics and steady-state) of SEV when compared with CON. SNP restored the PO(2mv) profile of SEV to that seen in Sham animals during CON. Specifically, the effect of L-NAME expressed as Delta(L-NAME - CON) were: Baseline PO(2mv) [in mmHg, DeltaSham = -7.0 +/- 1.6 (P < 0.05); DeltaSEV =-1.2 +/- 2.1], end-contractions PO(2mv) [in mmHg, DeltaSham = -5.0 +/- 1.0 (P < 0.05); DeltaSEV = -2.5 +/- 0.5] and time constant of PO(2mv) decrease [in s, DeltaSham = -6.5 +/- 3.0 (P < 0.05); DeltaSEV = -3.2 +/- 1.8]. CONCLUSION: These data provide the first direct evidence that the pathological profiles of PO(2mv) associated with severe CHF can be explained, in part, by a diminished vascular NO availability.

Animals↗
PubMed2006

Variability of antiepileptic medication taking behaviour in sudden unexplained death in epilepsy: hair analysis at autopsy.

BACKGROUND: Variable compliance with antiepileptic drugs (AEDs) is a potentially preventable cause of sudden unexplained death in epilepsy (SUDEP). Hair AED concentrations provide a retrospective insight into AED intake variability. METHODS: We compared hair AED concentration variability in patients with SUDEP (n = 16), non-SUDEP epilepsy related deaths (n = 9), epilepsy outpatients (n = 31), and epilepsy inpatients (n = 38). AED concentrations were measured in 1 cm hair segments using high performance liquid chromatography. Individual patient hair AED concentration profiles were corrected for "washout" using linear regression analysis. The coefficient of variation (CV) of the corrected mean hair AED concentration provided an index of variability of an individual's AED taking behaviour. Hair sample numbers varied between subjects, and so weighted regression estimates of the CV were derived for each group. RESULTS: The CV regression estimates for each group were: SUDEP 20.5% (standard error 1.9), non-SUDEP 15.0% (3.9), outpatients 9.6% (1.4), and inpatients 6.2% (2.7). The SUDEP group therefore showed greater hair AED concentration variability than either the outpatient or the inpatient groups (p<0.0001). CONCLUSION: Observed variability of hair AED concentrations, reflecting variable AED ingestion over time, is greater in patients dying from SUDEP than in either epilepsy outpatients or inpatients. SUDEP, at least in a proportion of cases, appears preventable.

Adolescent↗
PubMed2006

The Face-Symbol Test and the Symbol-Digit Test are not reliable surrogates for the Paced Auditory Serial Addition Test in multiple sclerosis.

The Paced Auditory Serial Addition Test (PASAT) is the chosen task for cognitive assessment in the multiple sclerosis functional composite (MSFC) and a widely used task in neuropsychological studies of people with multiple sclerosis (MS), but is unpopular with patients. The Face-Symbol Test (FST) and Symbol-Digit Tests (SDT) are alternative methods of cognitive testing in MS, which are easily administered and patient-friendly. In order to evaluate the potential of the FST as a possible surrogate for the PASAT, we directly compared the FST to the PASAT and the SDT in a cohort of 50 MS patients with varying levels of disability. There was significant correlation between SDT and FST scores (Spearman's rho 0.80, 95% CI 0.66-0.88), R(2) 65%, with moderate inter-test agreement (k =0.52). In contrast, SDT and FST scores were less predictive of PASAT scores. We concluded that neither the FST nor SDT are reliable surrogates for the PASAT.

Adult↗