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Biomedical subjects

C M Wilson

Publications and source records attributed to C M Wilson.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin 18 and human immunodeficiency virus type I infection in adolescents and adults.

Interleukin (IL)-18, a proinflammatory cytokine, has been recognized recently as an important factor in both treated and untreated patients with human immunodeficiency virus type 1 (HIV-1) infection. Consistent with all earlier reports, our quantification of serum IL-18 concentrations in 88 HIV-1 seropositive, North American adolescents (14-18 years old) revealed a positive correlation with cell-free HIV-1 viral load at two separate visits (Spearman's r = 0.31 and 0.50, respectively, P < 0.01 for both), along with a negative correlation with CD4+ T cell counts (r = -0.31 and -0.35, P < 0.01 for both). In additional analyses of 66 adults (21-58 years old) from Zambia, HIV-1 seroconversion was associated uniformly with elevated IL-18 production (P < 0.0001). These epidemiological relationships were independent of other population-related characteristics, including age, gender and ethnicity. In neither study population could serum IL-18 concentrations be associated with the IL-18 gene (IL18) promoter genotypes defined by five major single nucleotide polymorphisms. Collectively, these findings suggest that circulating IL-18 rather than the IL18 genotype may provide a useful biomarker for HIV-1-related events or outcomes.

ADP-ribosyl Cyclase 1↗
PubMed2005

Direct observation of dynamical bifurcation between two driven oscillation states of a Josephson junction.

We performed a novel phase-sensitive microwave reflection experiment which directly probes the dynamics of the Josephson plasma resonance in both the linear and the nonlinear regime. When the junction was driven below the plasma frequency into the nonlinear regime, we observed for the first time the transition between two different dynamical states predicted for nonlinear systems. In our experiment, this transition appears as an abrupt change in the reflected signal phase at a critical excitation power. This controlled dynamical switching can form the basis of a sensitive amplifier, in particular, for the readout of superconducting qubits.

Journal Article↗
PubMed2005

Interleukin (IL)-2 and IL-12 responses to Chlamydia trachomatis infection in adolescents.

Chlamydia trachomatis infects epithelial cells at the mucosal surface. While in vitro and animal studies have shown changes in mucosal T(H)1-associated cytokines in the presence of C. trachomatis infection and with its progression to the upper genital tract or clearance, in vivo cytokine responses to chlamydial infection in humans are not well understood. Using a quantitative enzyme-linked immunosorbent assay (ELISA), we examined the endocervical production of two T(H)1-associated cytokines, i.e. interleukin (IL)-2 and IL-12, in relation to C. trachomatis infection in adolescents. At a randomly selected visit for 396 females, median endocervical IL-2 levels were significantly lower (190 versus 283 pg/ml, P = 0.02) and median IL-12 levels significantly higher (307 versus 132 pg/ml, P < 0.001) in subjects testing positive versus negative for C. trachomatis. These divergent T(H)1-associated cytokine responses were: (1) confirmed in paired analyses of 96 individuals before and after infection within 6-month intervals, (2) reversible in 97 patients who cleared infection during consecutive visits, (3) not attributable to sociodemographic factors or other genital infections and (4) independent of common genetic variants at the IL2 and IL12B loci associated previously with differential gene expression. From these findings we infer that increased IL-12 and decreased IL-2, observed commonly during mucosal inflammation, are important features of mucosal immune defence against C. trachomatis infection.

Adolescent↗
PubMed2004

RF-driven Josephson bifurcation amplifier for quantum measurement.

We have constructed a new type of amplifier whose primary purpose is the readout of superconducting quantum bits. It is based on the transition of a rf-driven Josephson junction between two distinct oscillation states near a dynamical bifurcation point. The main advantages of this new amplifier are speed, high sensitivity, low backaction, and the absence of on-chip dissipation. Pulsed microwave reflection measurements on nanofabricated Al junctions show that actual devices attain the performance predicted by theory.

Journal Article↗
PubMed2004

Assessment of tracheal intubation in children after induction with propofol and different doses of remifentanil.

Tracheal intubating conditions were assessed in 112 children after induction of anaesthesia with propofol and remifentanil 1.0, 2.0 or 3.0 micro g.kg-1. Subjects in a control group were given propofol and mivacurium 0.2 mg.kg-1. Haemodynamic and respiratory parameters were recorded. Plasma catecholamine levels were measured in a subgroup of 40 children. Intubating conditions were acceptable in 14/28 (50%), 18/26 (69%) and 22/27 (82%) in those subjects given remifentanil 1.0, 2.0 or 3.0 micro g.kg-1, respectively, and in 27/28 (96%) of the control group. Intubating conditions in subjects given remifentanil 3.0 micro g.kg-1 were better than in those given remifentanil 1.0 micro g.kg-1 (p < 0.05). There were no significant differences in intubating conditions between those given remifentanil 3.0 micro g.kg-1 and the control group. Systolic blood pressure and heart rate increased in response to tracheal intubation in subjects given remifentanil 1.0 micro g.kg-1 and in the control group (p < 0.05). Time to resumption of spontaneous respiration was prolonged in subjects given remifentanil 3.0 micro g.kg-1 (p < 0.001). In conclusion, remifentanil 2 micro g.kg-1 provides acceptable intubating conditions and haemodynamic stability without prolonging the return of spontaneous respiration.

Analgesics, Opioid↗
PubMed2002

Increased resting bronchial tone in normal subjects acclimatised to altitude.

BACKGROUND: Normal subjects frequently experience troublesome respiratory symptoms when acclimatised to altitude. Bronchial hyperresponsiveness (BHR) and full and partial flow-volume loops were measured before and after ascent to 5000 m altitude to determine if there are changes in resting bronchial tone and BHR that might explain the symptoms. METHODS: BHR to histamine was measured using a turbine spirometer to record partial and full flow-volume curves and expressed as log dose slopes. Twenty one subjects were tested at sea level and after acclimatisation at 5000 m altitude. RESULTS: No significant change in log dose slope measurements of forced expiratory volume in 1 second occurred after acclimatisation, and the maximal expiratory flow with 30% of forced vital capacity remaining (MEF(30%)) rose on the full loop and fell on the partial loop. Their ratio (full divided by partial) rose on average by 0.28 (95% confidence limits 0.14 to 0.42) from the mean (SD) sea level value of 0.87 (0.20). CONCLUSIONS: There is no increase in BHR in normal subjects acclimatised to altitude but an increase in resting bronchial tone occurs that could be released by deep inspiration. This may be the result of increased cholinergic tone.

Adaptation, Physiological↗
PubMed2001

Cognitive impairment in sporadic ALS: a pathologic continuum underlying a multisystem disorder.

BACKGROUND: Traditionally considered a motor neuron-selective disorder, the clinical manifestations of ALS can include a frontotemporal dementia. Although the pathologic substrate of cognitive impairment remains to be defined, the presence of ubiquitin-immunoreactive (Ub+) intraneuronal inclusions in cortical regions has been suggested to constitute a pathologic marker of this process. METHODS: The authors compared the neuropathological features of four cognitively impaired patients with ALS, four cognitively intact patients with ALS, and four neurologically normal patients. The extent and load of Ub+ neuronal inclusions, Ub+ dystrophic neurites, and superficial linear spongiosis (SLS) was determined among a number of cortical, hippocampal, and subcortical regions. RESULTS: Although Ub+, alpha-synuclein-negative, and tau-negative neuronal inclusions were observed in both cognitively impaired and cognitively intact patients with ALS, their density and extent was greater among the former, with the difference greatest in the cingulate gyrus. Ub+ neurites were observed in a similar distribution. Only the presence of SLS, affecting the first and second cortical layers, reliably distinguished between the cognitively impaired and cognitively intact ALS subpopulations. In three of four cognitively impaired patients with ALS, SLS was associated with transcortical microglial activation, in the absence of detectable differences in astrocytosis, density of calbindin or parvalbumin neurons, or optical density of synaptophysin and SNAP-25. CONCLUSIONS: Although intraneuronal Ub+ inclusions and dystrophic neurites are observed in both ALS subpopulations, the presence of cognitive impairment was associated with a greater distribution and load of both neuropathologic features, suggesting a disease continuum. Moreover, cognitive impairment was uniformly associated with superficial linear spongiosis, a pathologic feature common to several forms of frontotemporal dementia.

Adult↗
PubMed2001

Time-resolved measurements of thermodynamic fluctuations of the particle number in a nondegenerate Fermi gas.

We report on time-resolved measurements of thermodynamic fluctuations in the number of particles in a nondegenerate Fermi gas. The gas is comprised of thermal quasiparticles, confined in a superconducting Al box by large-gap Ta leads. The average number of quasiparticles is about 10(5). This number fluctuates due to quasiparticle generation and recombination. The number is measured from the tunneling current through a barrier that bisects the box. The recombination time is independently measured by single-photon excitation and agrees with the frequency dependence of the fluctuations.

Journal Article↗
PubMed2001

An alternative method for delivering adrenocorticotropin hormone in birds.

In birds, intrajugular injection (i.j.) of exogenous adrenocorticotropin hormone (ACTH) has been used to challenge adrenocortical tissue when investigating various dynamics of the hypothalamic-pituitary-adrenal (HPA) axis. Although this method has been shown to deliver ACTH efficiently, i.j. injection can be difficult and potentially damaging to the bird, especially to young birds and small species. Intramuscular (i.m.) injection has been shown to be an alternative method for delivering ACTH to large birds; however, small songbirds have relatively less muscle mass in which to absorb i.m. injections and, in very small birds, even small needles may injure the delicate muscle tissue. Therefore, intraperitoneal (i.p.) administration of ACTH was investigated as a means of avoiding the potential problems associated with i.j. and i.m. injections when conducting adrenocortical pathway studies on small birds. Dark-eyed Juncos, Junco hyemalis, were first treated with dexamethasone to suppress the endogenous signal cascade for corticosterone release. Twelve hours later, birds were sampled for baseline corticosterone concentration and then immediately given an i.p. injection of either ACTH or physiological saline. A second blood sample was taken from all birds 30 min later to assess the effectiveness of i.p. ACTH administration on adrenocortical tissue. While saline-treated birds showed no significant increase in endogenous plasma corticosterone in response to the capture and handling protocol, ACTH-treated birds showed a significant increase in plasma corticosterone concentration, illustrating the effectiveness of the i.p. administration of exogenous ACTH. The adrenocortical response of ACTH-treated birds was similar in magnitude and rate of increase to that found in free-living, noninjected Juncos. Intraperitoneal injection of ACTH is thus a valid alternative to i.j. and i.m. injections when challenging adrenocortical tissue in small birds.

Adrenocorticotropic Hormone↗
PubMed2001

Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent Care and Health.

PURPOSE: To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS: Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS: Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS: The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

ADP-ribosyl Cyclase↗
PubMed2001

HIV-related oral manifestations among adolescents in a multicenter cohort study.

PURPOSE: To describe baseline prevalence of oral mucosal diseases among HIV infected adolescents in relationship to biological and behavioral risk factors. METHODS: Participants in Reaching for Excellence in Adolescent Care and Health (REACH), a multicenter longitudinal observational study of HIV/AIDS in adolescents, received physical examinations, blood tests, and oral examinations at 3-month intervals. We evaluated participants for oral conditions commonly seen in relationship to HIV, and explored the association of the most common lesion with selected biological and behavioral variables at baseline using contingency tables and Fisher's Exact test. RESULTS: Among 294 HIV infected adolescents recruited between March 1996 and March 1999, the majority were female (75%), aged 17 to 18 years (69%), and African-American (73%). More than 90% had a CD4(+) T-lymphocyte count > 200 cells/mm(3) at baseline and 57% had a plasma HIV-1 RNA concentration <or=5000 copies/mL. The most common condition was oral candidiasis (6%), predominantly the pseudomembranous type. The only variable found to be associated with oral candidiasis was elevated plasma HIV-1 RNA concentration (p = .03). Aside from 2 cases of hairy leukoplakia and aphthous ulcers, no other oral mucosal lesions were identified in this subject population with apparently early HIV disease. CONCLUSION: Similar types of oral lesions were observed in HIV infected adolescents as have been seen in adults, although the prevalence of these lesions was low. Elevated plasma HIV-1 RNA concentration was found to be associated with the baseline prevalence of oral candidiasis, and appeared to be a better predictor of HIV-related oral disease than CD4(+) T cell count in this cohort at early stage of HIV disease.

Adolescent↗
PubMed2001

Douching practices among HIV infected and uninfected adolescents in the United States.

PURPOSE: To characterize sexual behaviors and sociodemographic factors that are associated with douching among geographically diverse adolescent women with and without HIV infection. METHODS: HIV infected subjects recruited preferentially and behaviorally comparable high-risk HIV uninfected subjects were enrolled in a prospective HIV study from 15 sites in 13 U.S. cities. Baseline interview data from 1996 to 1999 for females aged 12 to 19 years were analyzed using one-way analysis of variance and multiple logistic regression. RESULTS: Among the 342 females/young women, 74.9% were black (non-Hispanic), 11.1% Hispanic/Latina, and 14.0% white or other race/ethnicity; 63.5% were HIV infected. Young women who had dropped out of high school comprised 23.4% of subjects. In the 3 months before the interview, 179 (52.3%) adolescents had douched at least once. In a multivariable logistic regression model, recent douching was more common among sexually active females (OR = 2.2; 95% CI: 1.2-4.2), Blacks (OR = 2.2; 95% CI: 1.2-4.1 vs. Hispanics/Whites/others), females who dropped out of high school (OR = 2.1; 95% CI: 1.2-3.7), and HIV infected females (OR = 1.7; 95% CI: 1.04-2.7). CONCLUSIONS: In this nationwide study, adolescents who are sexually active, African-American, dropped out of high school, and HIV infected were most likely to douche. Interventions to discourage douching should pay special attention to these populations.

Adolescent↗
PubMed2001

Sexually transmitted infections among HIV infected and HIV uninfected high-risk youth in the REACH study. Reaching for Excellence in Adolescent Care and Health.

OVERVIEW: This review presents the findings of published research in the Reaching for Excellence in Adolescent Care and Health (REACH) Project on sexually transmitted infections (STIs) within the context of the project's scientific agenda. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This review presents published analyses of cross-sectional data; longitudinal analyses are underway. In addition, baseline prevalence data on selected STIs and sexual risk profiles of the subjects in REACH are presented. High STI rates were evident in both human immunodeficiency virus (HIV) infected and uninfected youth of both genders regardless of sexual orientation. High infection rates at baseline suggest that prevention-oriented programs for risk reduction among adolescents should focus on both HIV infected and at-risk, uninfected youth.

Adolescent↗
PubMed2001

A purine-rich intronic element enhances alternative splicing of thyroid hormone receptor mRNA.

The mammalian thyroid hormone receptor gene c-erbAalpha gives rise to two mRNAs that code for distinct isoforms, TRalpha1 and TRalpha2, with antagonistic functions. Alternative processing of these mRNAs involves the mutually exclusive use of a TRalpha1-specific polyadenylation site or TRalpha2-specific 5' splice site. A previous investigation of TRalpha minigene expression defined a critical role for the TRalpha2 5' splice site in directing alternative processing. Mutational analysis reported here shows that purine residues within a highly conserved intronic element, SEa2, enhance splicing of TRalpha2 in vitro as well as in vivo. Although SEalpha2 is located within the intron of TRalpha2 mRNA, it activates splicing of a heterologous dsx pre-mRNA when located in the downstream exon. Competition with wild-type and mutant RNAs indicates that SEalpha2 functions by binding trans-acting factors in HeLa nuclear extract. Protein-RNA crosslinking identifies several proteins, including SF2/ASF and hnRNP H, that bind specifically to SEalpha2. SEalpha2 also includes an element resembling a 5' splice site consensus sequence that is critical for splicing enhancer activity. Mutations within this pseudo-5' splice site sequence have a dramatic effect on splicing and protein binding. Thus SEa2 and its associated factors are required for splicing of TRalpha2 pre-mRNA.

Alternative Splicing↗
PubMed2001

Antiretroviral medication adherence among the REACH HIV-infected adolescent cohort in the USA.

Adherence to highly active antiretroviral therapy (HAART) was investigated among HIV-infected adolescents recruited from 13 US cities into the REACH (Reaching for Excellence in Adolescent Care and Health) project, the first large-scale disease progression study of HIV-positive adolescents infected through sexual behaviour or injection drug use. Of 161 subjects, 7% could not correctly identify all their prescribed medications; 11% could identify them but reported never taking at least one medication. The majority (83%) reported taking all of their medications at least some of the time, but only 50% of these subjects reported full adherence. Therefore, only 41% of the sample reported full adherence. A strong association was found between adherence and reduced viral load. A CD4 level of > or = 500 cells/mm3 was also associated with adherence. Higher levels of depression were significantly associated with decreased adherence, and a trend was found for an association between number of medications prescribed and adherence. Strict adherence to HAART is critical for sustained suppression of viral replication allowing for immune recovery and reducing the risk of the selection of antiviral resistance. Adherence appears to be a serious problem among HIV-positive adolescents. Better education, intervention to relieve depression, and efforts to improve ease of medication use are essential.

Adolescent↗
PubMed2001

Performance of antigens used in detecting delayed-type hypersensitivity in adolescents infected with the human immunodeficiency virus.

We examined the performance of delayed-type hypersensitivity (DTH) antigens employing a new Candida albicans product in a human immunodeficiency virus (HIV)-infected and nonanergic adolescent population. Diameters of induration (in millimeters) for three intradermally applied antigens (C. albicans, tetanus toxoid, and mumps) were compared in a population of HIV-infected 12 to 18 year olds at study entry in a national multicenter study of HIV disease progression. CD4+ T-cell counts were measured in quality-controlled laboratories. The influence of past immunization, gender, and clinical status on antigen reactivity was evaluated with contingency table comparisons and relative risk estimation. Nearly one-half of the 123 eligible subjects were untreated, and almost three-quarters were early in HIV disease by clinical indicators. There was no statistically significant difference in reactivity by past immunization status. Candida antigen (CASTA; Greer Laboratories) evoked DTH response in a significantly higher number of males and females at every level of induration (largest P value, 0.049 for male comparisons; all P values, <0.001 for females) and in subjects with early and intermediate HIV disease at every level of induration (all P values, <0.0001) than either tetanus or mumps antigens. No two-antigen combination was as useful as all three antigens across either gender or clinical categories, although candida and tetanus was the most useful two-antigen combination at indurations of <3 mm. The superior performance of a new C. albicans antigen may extend the utility of DTH assessment in monitoring immune function.

Adolescent↗
PubMed2001

Physiological relationships between central vascular haemodynamics and left ventricular structure.

Left ventricular hypertrophy is an independent cardiovascular risk factor. In hypertensives, the pattern of hypertrophy is influenced by central haemodynamic characteristics. Central haemodynamics may also determine physiological differences in left ventricular structure and predispose to particular responses of the left ventricle to pathological increases in load. M-mode echocardiography was used to measure left ventricular diastolic dimension and to estimate left ventricular mass index, relative wall thickness and stroke volume in 159 healthy volunteers aged between 19 and 74 years. Tonometric sphygmography was used to estimate augmentation index, central end-systolic and mean arterial blood pressure. Effective arterial elastance was calculated as the ratio of end-systolic pressure to stroke volume. Left ventricular mass index and relative wall thickness were adjusted for variation in age, sex and blood pressure before analyses. Left ventricular diastolic dimension exhibited significant inverse correlations with both effective arterial elastance (r=-0.72, P<0.0001) and augmentation index (r=-0.23, P=0.004). Adjusted left ventricular mass index was inversely correlated with effective arterial elastance (r=-0.35, P<0.0001), but no correlation was observed between left ventricular mass index and augmentation index (r=0.04). Adjusted relative wall thickness correlated with increasing effective arterial elastance (r=0.32, P<0.0001) and augmentation index (r=0.18, P=0.02). Relative wall thickness (r=0.34, P<0.0001), but not left ventricular mass index, correlated with age. Higher elastance and augmentation correlates with relatively smaller left ventricular cavity size but larger relative wall thickness. Age-related changes in left ventricular afterload may affect relative wall thickness more significantly than left ventricular mass index and may contribute to a particular change in left ventricular geometry with age.

Adult↗