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Biomedical subjects

C Moore

Publications and source records attributed to C Moore.

At least 37 records · Page 2Linked to original sources
PubMed1998

Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine.

OBJECTIVE: To determine whether children with recurrent respiratory infections who failed to respond to the conventional polysaccharide vaccine would respond to a pneumococcal conjugate vaccine. METHODS: Children referred to our clinic for recurrent respiratory infections who had no known primary or secondary immunodeficiencies were immunized with a 23-valent pneumococcal polysaccharide vaccine. IgG antibodies to pneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme-linked immunosorbent assay before and 4 to 6 weeks after immunization. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer > or =1.3 microg/ml or at least 4 times the preimmunization value. Immunization with an experimental CRM197-heptavalent pneumococcal conjugate vaccine was offered to patients without an adequate response to 4 or more vaccine serotypes (nonresponders). Post-conjugate immunization antibody concentrations were measured 4 to 6 weeks later. RESULTS: In nonresponder patients (n = 17) geometric mean post-conjugate immunization (C) serum antibody concentrations (microg/ml) compared with post-polysaccharide (PS) concentrations were: (serotype, C vs. PS) 4, 1.11 vs. 0.30 (P = 0.000227); 6B, 0.46 vs. 0.20 (P = 0.017267); 9V, 0.82 vs. 0.29 (P = 0.002163); 14, 1.88 vs. 0.27 (P = 0.000615); 18C, 0.98 vs. 0.32 (P = 0.021962); 19F, 1.24 vs. 0.34 (P = 0.002844); and 23F, 0.87 vs. 0.16 (P = 0.000194). In responder patients (n = 67), after 1 dose of the polysaccharide vaccine, geometric mean antibody concentrations were: 4, 1.05; 6B, 0.96; 9V, 1.55; 14, 1.65; 18C, 1.62; 19F, 1.30; and 23F, 1.02. CONCLUSIONS: Our results show that a pneumococcal conjugate vaccine is capable of inducing an IgG response in patients with recurrent infections who had failed to mount an adequate response to the polysaccharide vaccine. Conjugate vaccines may be of value in the management of children with recurrent pneumococcal respiratory infections.

Adolescent↗
PubMed1998

Processivity of the Saccharomyces cerevisiae poly(A) polymerase requires interactions at the carboxyl-terminal RNA binding domain.

The interaction of the Fip1 subunit of polyadenylation factor I with the Saccharomyces cerevisiae poly(A) polymerase (PAP) was assayed in vivo by two-hybrid analysis and was found to involve two separate regions on PAP, located at opposite ends of the protein sequence. In vitro, Fip1 blocks access of the RNA primer to an RNA binding site (RBS) that overlaps the Fip1 carboxy-terminal interaction region and, in doing so, shifts PAP to a distributive mode of action. Partial truncation of this RBS has the same effect, indicating that this site is required for processivity. A comparison of the utilization of ribo- and deoxyribonucleotides as substrates indicates the existence on PAP of a second RBS which recognizes the last three nucleotides at the 3' end of the primer. This site discriminates against deoxyribonucleotides at the 3' end, and interactions at this site are not affected by Fip1. Further analysis revealed that the specificity of PAP for adenosine is not simply a function of the ATP binding site but also reflects interactions with bases at the 3' end of the primer and at another contact site 14 nucleotides upstream of the 3' end. These results suggest that the unique specificity of PAP for ribose and base, and thus the extent and type of activity with different substrates, depends on interactions at multiple nucleotide binding sites.

Binding Sites↗
PubMed1998

Transcription termination downstream of the Saccharomyces cerevisiae FBP1 [changed from FPB1] poly(A) site does not depend on efficient 3'end processing.

Efficient transcription termination downstream of poly(A) sites has been shown to correlate with the strength of an upstream polyadenylation signal and the presence of a polymerase pause site. To further investigate the mechanism linking termination with 3'-end processing, we analyzed the cis-acting elements that contribute to these events in the Saccharomyces cerevisiae FBP1 gene. FBP1 has a complex polyadenylation signal, and at least three efficiency elements must be present for efficient processing. However, not all combinations of these elements are equally effective. This gene also shows a novel organization of sequence elements. A strong positioning element is located upstream, rather than downstream, of the efficiency elements, and functions to select the cleavage site in vitro and in vivo. Transcription run-on analysis indicated that termination occurs within 61 nt past the poly(A) site. Deletion of two UAUAUA-type efficiency elements greatly reduces polyadenylation in vivo and in vitro, but transcription termination is still efficient, implying that FBP1 termination signals may be distinct from those for polyadenylation. Alternatively, assembly of a partial, but nonfunctional, polyadenylation complex on the nascent transcript may be sufficient to cause termination.

Base Sequence↗
PubMed1998

Increased circulating levels of soluble HLA class I heterodimers in patients with sickle cell disease.

This study examined the presence of a persistent state of low-grade inflammation in sickle cell anemia patients by measuring circulating sHLA-I heterodimers and C-reactive protein during the steady state and after recent crises. Thirty-nine pediatric sickle hemoglobinopathy patients were studied during the steady state and 11 patients were evaluated within 1 month of a painful crisis. A disease severity score was generated for each patient, and soluble HLA-I (sHLA-I) and C-reactive protein levels were determined. Soluble HLA-I was significantly elevated in 55% of the steady-state group and in 36% of the recent-crisis group. The percentage of patients with elevated sHLA-I differed in the various disease subgroups in the steady state: 46% of Hb SS patients, 70% of Hb SC patients, 75% of Hb S beta-thal patients, and 20% of Hb SSF patients. Steady-state and recent-crisis sHLA-I levels were not significantly different. C-reactive protein levels were elevated in 11% of steady-state patients and in 9% of recent-crisis patients. Soluble HLA-I levels did not correlate with C-reactive protein levels or disease severity score, age, hemoglobin, reticulocyte count, platelet count, or white cell count. These results show that the majority of sickle hemoglobinopathy patients have elevated sHLA-I levels during the steady state and after recent crisis, suggesting the presence of chronic inflammation during the steady state.

Anemia, Sickle Cell↗
PubMed1998

Targets and cues: gaze-following in children with autism.

Children with autism are known to have difficulties in sharing attention with others. Yet one joint attention behaviour, the ability to follow another person's head turn and gaze direction, may be achieved without necessarily sharing attention. Why, then, should autistic children have difficulties with it? In this study we examined the extent of this difficulty by testing school-aged autistic children across three different contexts; experiment, observation, and parent interview. We also tested whether the ability to orient to another person's head and gaze could be facilitated by increasing children's attention to environmental targets and social cues. Results for experiment and observation demonstrate that a sizeable proportion of children with autism did not have difficulties with following another's head turn. There was a difference between children with high and low verbal mental ages, however. Whereas children with higher mental ages (over 48 months) were able to orient spontaneously to another person's head turn, children with lower mental ages had difficulties with this response. When cues were added (pointing, language) or when feedback from targets was given, however, their performance improved. Parent interview data indicated that children with autism, whatever their mental age, began to follow head turn and gaze direction years later than typically developing children. Developments in attention and language are proposed as possible factors to account for this developmental delay.

Age Factors↗
PubMed1998

Attachment and adolescent psychosocial functioning.

To explore the meaning and function of attachment organization during adolescence, its relation to multiple domains of psychosocial functioning was examined in a sample of 131 moderately at-risk adolescents. Attachment organization was assessed using the Adult Attachment Interview; multiple measures of functioning were obtained from parents, adolescents, and their peers. Security displayed in adolescents' organization of discourse about attachment experiences was related to competence with peers (as reported by peers), lower levels of internalizing behaviors (as reported by adolescents), and lower levels of deviant behavior (as reported by peers and by mothers). Preoccupation with attachment experiences, seen in angry or diffuse and unfocused discussion of attachment experiences, was linked to higher levels of both internalizing and deviant behaviors. These relations generally remained even when other attachment-related constructs that had been previously related to adolescent functioning were covaried in analysis. Results are interpreted as suggesting an important role for attachment organization in a wide array of aspects of adolescent psychosocial development.

Adolescent↗
PubMed1997

Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone.

Uncoupling protein (UCP1) is a transmembrane proton transporter present in the mitochondria of brown adipose tissue (BAT), a specialized tissue which functions in temperature homeostasis and energy balance (Nicholls, D. G., and Locke, R. M. (1984) Physiol. Rev. 64, 2-40; Lowell, D. D., and Flier, J. S. (1997) Annu. Rev. Med.). UCP1 mediates the thermogenesis that is characteristic of BAT by uncoupling mitochondrial oxidation of substrates from ATP synthesis. Recently, two proteins related to UCP1 have been identified and designated UCP2 (Fleury, C., et al. (1997) Nature Genetics 15, 269-272) or UCP homolog (UCPH) (Gimeno, R. E., et al. (1997) Diabetes 46, 900-906) and UCP3 (Boss, O., et al. (1997) FEBS Lett. 408, 39-42; Vidal-Puig, A., et al. (1997) Biochem. Biophys. Res. Commun. 235, 79-82). We investigated the regulation in rats of UCP3, which is expressed primarily in skeletal muscle and BAT. Expression of rat UCP3 mRNA in BAT was upregulated by in vivo treatment with triiodothyronine (T3) and by exposure to cold, suggesting that UCP3 is active in thermogenesis and energy expenditure. In skeletal muscle, UCP3 mRNA was also upregulated by T3 but, surprisingly, not by cold exposure. A hypothesis is proposed to account for this differential regulation.

Adipose Tissue, Brown↗
PubMed1997

Tyrosinium-D-tetrahydroisoquinoline-3-carboxylate 1.5-hydrate and tyrosyl-D-tetrahydroisoquinoline-3-carboxamide hydrate.

Crystals of the two dipeptide title compounds, Tyr-D-Tic, C19H20N2O4.1.5H2O, and Tyr-D-Tic-NH2, C19H21N3O3.H2O, were prepared by the sitting-drop method. Tyr-D-Tic is orthorhombic (P2(1)2(1)2(1)) and crystallizes as a zwitterion. The asymmetric unit contains two peptide molecules and three molecules of water. Tyr-D-Tic-NH2 crystals are monoclinic (P2(1)), the asymmetric unit containing one peptide molecule and one molecule of water. Despite some differences in packing, the conformation of the two dipeptides is almost identical (r.m.s. deviation for non-H atoms is approximately 0.18 A).

Crystallography, X-Ray↗
PubMed1997

Relation between bed use, social deprivation, and overall bed availability in acute adult psychiatric units, and alternative residential options: a cross sectional survey, one day census data, and staff interviews.

OBJECTIVES: To examine the relation between bed use, social deprivation, and overall bed availability in acute adult psychiatric units and to explore the range of alternative residential options. DESIGN: Cross sectional survey, combined with one day census data; ratings by and interviews with staff; examination of routine data sources. SETTINGS: Nationally representative sample of acute psychiatric units. SUBJECTS: 2236 patients who were inpatients on census day. MAIN OUTCOME MEASURES: Bed occupancy levels, judged need for continuing inpatient care, reasons preventing discharge, scores on the Health of the Nation outcome scales. RESULTS: Bed occupancy was related to social deprivation and total availability of acute beds (r = 0.66, 95% confidence interval 0.19 to 0.88, F = 8.72, df = 2.23; P = 0.002). However, 27% (603/2215) of current inpatients (61% (90/148) of those with stays of > 6 months) were judged not to need continuing admission. The major reasons preventing discharge were lack of suitable accommodation (37% (176/482) of patients in hospital < 6 months v 36% (31/86) of those in hospital > 6 months); inadequate domiciliary based community support (23% (113) v 9% (8)); and lack of long term rehabilitation places (21% (100) v 47% (40)). Scores on the Health of the Nation outcome scale were generally consistent with these staff judgments. CONCLUSIONS: The shortage of beds in acute psychiatric units is related to both social deprivation and the overall availability of acute beds. Patients currently inappropriately placed on acute admission wards should be relocated into more suitable accommodation, either in hospital or in the community. A range of provisions is required; simply providing more acute beds is not the answer.

Acute Disease↗
PubMed1997

Determination of drug exposure using hair: application to child protective cases.

The use of hair as a specimen for the determination of drug use remains controversial. Scientists disagree upon whether environmental drug contamination (e.g. smoke) can be differentiated from actual drug use. Children whose parents use drugs (particularly crack) at home are considered to be at risk. Using the hair of the children to determine exposure gives extra credibility to the child protective services and allows them to remove children from dangerous households. Children are tested when there are credible reasons for suspecting drug exposure. In Blackhawk Country, Iowa, this program was implemented in late 1994, and since then many children have tested positively for drugs, the majority of the hair containing cocaine or methamphetamine. In some cases, cocaethylene and benzoylecgonine were also found in the hair of the children. While the presence of benzoylecgonine can be explained by exposure to crack smoke, the presence of cocaethylene suggests ingestion of cocaine and alcohol. Blackhawk Country Juvenile Court have found the program to be so useful in helping children, that they have extended hair testing from Child Protective allegation investigations to ongoing court cases and even delinquency hearings.

Adolescent↗
PubMed1997

Integrating relationship constructs and emotional experience into false belief tasks in preschool children.

Themes of separation from attachment figures are involved when caregivers are integrated into standard theory of mind tasks in which objects or toys are located. Two experiments test the hypothesis that searching for a caregiver would interfere with false belief performance and be related to a child's emotional awareness. Experiment 1 consisted of a cross-sectional study of three- to five-year-old children administered false belief tasks related to object identity, object location, and caregiver location, i.e., false belief tasks where story characters became separated from a parent and had to locate them. As expected, there were age-related improvements in false belief performance to above-chance levels during object identity and object location tasks, but performance on the caregiver location tasks showed no age-related improvement and at age five was poorer than other tasks. Emotional integration also varied with task. Children who were relatively more aware of emotions were more likely to pass tasks involving objects, and queries of emotions during tasks were related to false beliefs about objects but not caregivers. A second study of children five years of age indicated that it was not caregivers per se that disrupted their performance on false belief tasks. Additional tasks showed that this finding was due to caregivers being animate "behaving" objects whose relocation had been self- as opposed to other-directed, which suggests that false belief performance was related to the intent of the sought item. The developing awareness of the minds of others in five-year-olds and emotional content of the task may interfere with performance in false belief tasks that are social.

Affect↗
PubMed1997

Double-blind, randomized, placebo controlled study on the effects of the monophasic oral contraceptive containing 30 micrograms ethinyl estradiol and 2.00 mg dienogest on the hemostatic system.

Forty healthy female volunteers aged between 19 and 35 years (27.3 +/- 4.1 years) with normal menstrual cycles were included in a double-blind, randomized, placebo-controlled study to investigate the influence on the hemostatic system of an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest, which is a 19-norprogestin without a 17 alpha-ethinyl group. At baseline and during one treatment cycle, 12 hemostatic parameters were measured on cycle days 7, 14, and 21. The hemostatic parameters were categorized as either procoagulatory, anticoagulatory and profibrinolytic, or antifibrinolytic and indicative of fibrin turnover. Differences between placebo and 30 micrograms ethinyl estradiol and 2.00 mg dienogest of plasma levels of hemostatic parameters on cycle days 21 of the precycle and treatment cycle were chosen as target variables. Prothrombin fragment 1 + 2 (F 1 + 2) was chosen as the main target variable. Equivalence of F 1 + 2 between placebo and active treatment was noted. Among the procoagulatory factors, only factor VII activity was found to be increased over placebo in the active treatment group, but decreased in the placebo group. Protein C activity increased during the treatment with 30 micrograms ethinyl estradiol and 2.00 mg dienogest, and was higher than that of the placebo group in which this parameter decreased during the treatment cycle. There was a corresponding increase in fibrinolytic activity being reflected by higher plasminogen levels in the active treatment group in comparison with placebo. An increase was noted for the fibrinolytic parameter D-dimer. Apart from isolated measurements, the parameters remained in their respective normal ranges. The data combine to suggest that 30 micrograms ethinyl estradiol and 2.00 mg dienogest has a balanced effect on the hemostatic system stimulating both procoagulatory and fibrinolytic activity.

Adult↗
PubMed1997

Modulation of ovarian function by an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest.

Twenty-two healthy female volunteers with normal ovulatory cycles, aged between 20 and 34 years (27.3 +/- 4.1), were included in a single-center, noncomparative study to investigate the modulation of ovarian function by an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest. At baseline, during three treatment cycles and post-treatment, serum levels of luteinizing hormone, follicle-stimulating hormone, 17 beta-estradiol, and progesterone were assayed and ultrasonography was used to measure follicular size and the thickness of the endometrium. The primary efficacy variable was inhibition of ovulation as measured by ovarian activity grading. All volunteers ovulated during the pretreatment cycle. During treatment, none of the subjects had ovulatory cycles, although there was still some ovarian activity in several subjects. During the first treatment cycle, only 4% (1 subject) of cycles showed active follicle-like structures. The frequency of follicle-like structures increased to 33% and 35% during treatment cycles 2 and 3. The frequency of presumptive luteinized unruptured follicle-like structures was 5% (1 subject) and 15% (3 subjects) in treatment cycles 2 and 3. The serum hormone concentrations were effectively suppressed in comparison to baseline. The ovarian activity returned to baseline during the post-treatment period. One subject was excluded from further study because of a medical problem believed unrelated to use of the oral contraceptive. No serious adverse events were recorded during the course of the study. The results of the present investigation indicate that the modulatory effects on ovarian function of the monophasic oral-contraceptive containing 30 micrograms ethinyl estradiol combined with 2.00 mg dienogest lead to adequate suppression of ovarian activity and effective inhibition of ovulation.

Adult↗
PubMed1997

Low-dose methotrexate therapy for childhood sarcoidosis.

OBJECTIVE: To evaluate the effectiveness of low oral doses of methotrexate as a steroid-sparing agent in children with sarcoidosis. STUDY DESIGN: An open-label, noncontrolled trial. Methotrexate was administered orally at a single weekly dose of 10 to 15 mg/m2. Duration of therapy was open ended, but patients received treatment for a minimum of 6 months to be considered as having completed the study. RESULTS: Seven children with biopsy-proven sarcoidosis completed the study. The mean dose of prednisone was successfully tapered from 49 mg/day (1.3 mg/kg) to 18 mg/day (0.5 mg/kg) after 3 months of methotrexate therapy and to 9.9 (0.2 mg/kg) and 7.3 mg/day (0.1 mg/kg) after 6 months and at the end of the follow-up period, respectively. Other clinical and laboratory parameters improved significantly after methotrexate therapy was started. There was significant clinical improvement, as confirmed by the reduction of the clinical severity score from 8 +/- 1.1 to 0.8 +/- 0.5 point after 3 months of methotrexate therapy, and to 0.7 and 0.5 +/- 0.3 point after 6 months and at the end of the follow-up, respectively. Laboratory measurements revealed marked improvement, as reflected by a significant reduction in the erythrocyte sedimentation rate and an increase of hemoglobin values. The mean serum angiotensin-converting enzyme activity dropped significantly. No adverse side effects were noted with methotrexate therapy. CONCLUSION: Our study demonstrated that low-dose oral methotrexate therapy was effective and safe and had steroid-sparing properties in seven children with sarcoidosis.

Administration, Oral↗
PubMed1997

Elevated levels of soluble HLA class I (sHLA-I) in children with severe atopic dermatitis.

BACKGROUND: Atopic dermatitis is characterized by increased production of IgE and interleukin-4, immediate skin test reactivity to allergens, increased expression of CD23 on mononuclear cells, and decreased production of interferon-gamma. Soluble HLA-I molecule levels are elevated in conditions where T cells are activated such as viral infections, autoimmune diseases, and organ transplantation. OBJECTIVE: We wished to determine if sHLA-I heterodimers were also elevated in patients with atopic dermatitis and if sHLA-I elevations correlated with disease activity. METHODS: Fourteen children with atopic dermatitis resistant to conventional treatment were followed over an 8-week period during an ongoing trial of treatment with topical sodium cromoglycate. Extent of skin involvement, disease severity, absolute eosinophil counts, IgE and HLA-I levels were determined at the time of enrollment into the study. Additional sHLA-I levels were measured after 4 and 8 weeks of therapy. RESULTS: Mean sHLA-I levels were significantly elevated in atopic dermatitis patients, 2.07 +/- 1.14 versus 1.00 +/- 0.22 microg/mL in controls (P < .0001). Nine of 14 patients (64%) had elevated sHLA-I antigens. Soluble HLA-I levels did not correlate with the extent of disease, disease severity score, eosinophil count, or IgE levels. There was a remarkable consistency in sHLA-I levels at baseline and after 4 and 8 weeks of therapy, even with significant clinical improvement. CONCLUSION: We conclude that sHLA-I heterodimers are elevated in 64% of our patients with atopic dermatitis and that elevations persist after clinically effective therapy. This conclusion supports recommendations for prolonged preventative and treatment measures in this atopic disease.

Child↗
PubMed1997

Effect of low dose oxandrolone and testosterone treatment on the pituitary-testicular and GH axes in boys with constitutional delay of growth and puberty.

OBJECTIVE: To investigate the effect of low dose oxandrolone and testosterone on the pituitary-testicular and GH-IGF-I axes. DESIGN: Prospective double-blind placebo-controlled trial. PATIENTS: Sixteen boys with constitutional delay of growth and puberty (CDGP) with testicular volumes 4-6 ml were randomized to 3 months treatment: Group 1 (n = 5), daily placebo: Group 2 (n = 5), 2.5 mg oxandrolone daily or Group 3 (n = 6), 50 mg testosterone monthly intramuscular injections with assessment (growth, pubertal development and overnight hormone profiles) at 0, 3, 6 and 12 months. MAIN OUTCOME MEASURES: LH and GH profiles (15-minute samples) were analysed by peak detection (Pulsar), Fourier transformation and autocorrelation. Testosterone levels were measured hourly and insulin, SHBG, IGF-I, and IGFBP-3 levels at 0800 h. Statistical analysis was by multivariate analysis of variance for repeated measures. RESULTS: LH and testosterone parameters increased significantly with time in all 16 (LH AUC, P < 0.001; peak amplitude, P = 0.02; number of peaks, P = 0.02; testosterone AUC, P = 0.02; morning testosterone, P = 0.002). In Group 2, however, LH and testosterone parameters decreased at 3 months followed by a rebound increase at 6 and 12 months. SHBG levels were markedly reduced at 3 months (P = 0.006) and a wider range of dominant GH frequencies was present although GH AUC was not increased until 6 months, with an increase in GH pulse frequency but not amplitude. IGF-I levels were increased at both 3 and 12 months. In Group 3, pituitary-testicular suppression was not apparent, but GH levels increased with an increase in GH amplitude at 3 and 12 months. CONCLUSION: Oxandrolone transiently suppressed the pituitary-testicular axis and altered GH pulsatility. Testosterone increased GH via amplitude modulation.

Adolescent↗