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J C Craig

Publications and source records attributed to J C Craig.

At least 73 records · Page 4Linked to original sources
PubMed2000

Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation.

Phosphorylation of the transcription factor CREB leads to the recruitment of the coactivator, CREB binding protein (CBP). Recent studies have suggested that CBP recruitment is not sufficient for CREB function, however. We have identified a conserved protein-protein interaction motif within the CBP-binding domains of CREB and another transcription factor, SREBP (sterol-responsive element binding protein). In contrast to CREB, SREBP interacts with CBP in the absence of phosphorylation. We have exploited the conservation of this interaction motif to test whether CBP recruitment to CREB is sufficient for transcriptional activation. Substitution of six nonconserved amino acids from SREBP into the activation domain of CREB confers high-affinity, phosphorylation-independent CBP binding. The mutated CREB molecule, CREB(DIEDML), activates transcription in F9 teratocarcinoma and PC12 cells even in the absence of protein kinase A (PKA). Addition of exogenous CBP augments the level of transcription mediated by CREB(DIEDML), and adenovirus 12S E1A blocks transcription, implicating CBP in the activation process. Thus, recruitment of CBP to CREB is sufficient for transcriptional activation. Addition of PKA stimulates transcription induced by CREB(DIEDML) further, suggesting that a phosphorylation event downstream from CBP recruitment augments CREB signaling.

Amino Acid Sequence↗
PubMed2000

Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomised controlled trials.

AIMS: To determine the benefits and toxicity of different corticosteroid regimes in preventing relapse in steroid responsive nephrotic syndrome. DESIGN: Meta-analysis of randomised controlled trials. SUBJECTS: Twelve trials involving 868 children aged 3 months to 18 years. MAIN OUTCOME MEASURE: Frequency of relapse. RESULTS: A meta-analysis of five trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12-24 months (relative risk 0.73; 95% confidence interval 0.60 to 0.89) without an increase in adverse events. There was an inverse linear relation (relative risk 1.382 (SE 0.215) - 0.133 (SE 0.048) duration; r(2) = 0.66; p = 0.05) between the duration of treatment and risk of relapse. CONCLUSIONS: Children in their first episode of steroid responsive nephrotic syndrome should be treated with prednisone for at least three months, with an increase in benefit being shown for up to seven months of treatment.

Adolescent↗
PubMed2000

Does treatment of vesicoureteric reflux in childhood prevent end-stage renal disease attributable to reflux nephropathy?

OBJECTIVE: It is believed that end-stage renal disease (ESRD) attributable to reflux nephropathy is preventable by the active treatment of vesicoureteric reflux in childhood with long-term antibiotics and ureteric reimplantation surgery. We aimed to test this belief. METHODOLOGY: The Australia and New Zealand Dialysis and Transplant Registry of new patients 5 to 44 years of age treated for ESRD between 1971 and 1998, categorized by age and primary renal disease, was used to analyze the age-specific incidences of ESRD attributable to reflux nephropathy using a before-after study design. The early 1960s were regarded as the introduction period for the active treatment of childhood vesicoureteric reflux. A time-delay in treatment effect was expected. Patients with ESRD attributable to other causes were used as a comparative group. RESULTS: The incidence of ESRD attributable to reflux nephropathy and nonreflux nephropathy has increased. For reflux nephropathy, the rate of change was significantly associated with age, with a downward trend in incidence with decreasing age suggesting a minor treatment effect. This trend was no longer evident when adjustment was made for changing diagnostic practices. An opposite trend was observed for the nonreflux nephropathy group, who demonstrated an upward trend in incidence with decreasing age. CONCLUSIONS: Treatment of children with vesicoureteric reflux has not been accompanied by the hoped-for reduction in the incidence of ESRD attributable to reflux nephropathy. A randomized trial with a control (no-treatment) arm is required to appropriately assess the medical belief that long-term antibiotics and surgery improve the natural history of vesicoureteric reflux.

Adolescent↗
PubMed2000

Processing of sequential tactile patterns: effects of a neutral stimulus.

The perception of a target pattern may be interfered with by the presentation of a nontarget pattern in close temporal and spatial proximity with it. The results from previous studies suggested that much of this interference is the result not of masking but of response competition, subjects responding with the nontarget instead of the target. Using a 4-to-2 paradigm in which four target patterns are mapped onto two responses, it was shown that neutral patterns (i.e., patterns with no responses associated with them) produce considerable interference. The amount of interference is less than that produced by patterns associated with incorrect responses but greater than that produced by patterns associated with correct responses. The amount of interference produced by neutral patterns did not vary as a function of the form of the neutral pattern (Experiments 1 and 2); however, the amount of interference did depend on the degree and nature of the similarity between the neutral and target patterns (Experiments 3 and 4). The results indicate that recent studies have underestimated the amount of interference due to masking and overestimated the amount due to response competition. Response competition may either hinder or help target categorization depending on the nontarget pattern.

Adolescent↗
PubMed2000

Rapid hot dog surface pasteurization using cycles of vacuum and steam to kill Listeria innocua.

The vacuum/steam/vacuum surface pasteurization process was applied to hot dogs inoculated on the surface with non-pathogenic Listeria innocua. Using the optimum conditions previously found for processing chicken carcasses as a starting point, optimum process conditions were determined for a hot dog treatment compatible with current process line speed. Cycling the treatment significantly improved the microbiological kill. At the optimum conditions of steam time of 0.3 s at 138 degrees C (two cycles), a bacteria kill >3 log CFU/ml was attained. Pasteurization, frequently considered to be a kill of >5 log CFU/ml, was reached by increasing the number of cycles to three. The surface pasteurization process should ensure that hot dogs reaching the consumer are free of Listeria.

Animals↗
PubMed2000

How accurate is dimercaptosuccinic acid scintigraphy for the diagnosis of acute pyelonephritis? A meta-analysis of experimental studies.

UNLABELLED: The purpose of this study was to evaluate the performance of dimercaptosuccinic acid (DMSA) scintigraphy in the diagnosis of acute pyelonephritis and to compare the test performance of the standard technique, planar DMSA, with the newly introduced technique, SPECT DMSA. METHODS: All published animal studies in which DMSA scintigraphy was compared with histopathology, the reference standard for acute pyelonephritis, were identified using a comprehensive search strategy with the MEDLINE and EMBASE databases. Test performances of all DMSA methods and SPECT versus planar DMSA were analyzed using summary receiver operating characteristic (sROC) curves. RESULTS: Seven studies were identified, including 2 of SPECT DMSA. Problems in study design or reporting were common, with numerical errors in 4 studies. Overall, at a sensitivity of 86%, specificity was estimated to be 91%. Detection of acute pyelonephritis was at a lower threshold for SPECT than for planar DMSA (sensitivity/specificity values of 97%0/66% compared with 82%/ 97%), and the overall test performance of SPECT was not demonstrably better than that of planar DMSA. When applied to a group of children with a prevalence of renal damage of 40%, this means that 98% of children with abnormal planar DMSA scans will have renal damage, whereas only 65% of those with abnormal SPECT scans will have renal damage. Planar and SPECT DMSA will miss 11% and 3% of children with renal damage, respectively. Out of 100 children in the hypothetical group with 40% experiencing renal damage, SPECT will identify 6 extra true cases of renal damage at the expense of 19 extra false positives, when compared with planar DMSA. CONCLUSION: Published studies of DMSA test performance are few in number and have significant methodologic problems that should be avoided in future studies. DMSA, particularly the planar technique, performs well for the diagnosis of acute pyelonephritis. Using test performance criteria, SPECT DMSA alone has not been shown to be preferable to the established planar method and will result in a small number of true-positives at the expense of a larger number of false-positives.

Acute Disease↗
PubMed1999

Grating orientation as a measure of tactile spatial acuity.

Recent studies have used grating orientation as a measure of tactile spatial acuity on the fingerpad. In this task subjects identify the orientation of a grooved surface presented in either the proximal-distal or lateral-medial orientation. Other recent results have suggested that there might be a substantial anisotropy on the fingerpad related to spatial sensitivity. This anisotropy was revealed using a task in which subjects discriminated between a smooth and a grooved surface presented at different orientations on the fingerpad. The anisotropy was substantial enough that it might permit subjects to discriminate grating orientation on the basis of intensive rather than spatial cues. The present study examined the possibility that anisotropy on the fingerpad might provide cues in a spatial acuity task. The ability of subjects to discriminate between a smooth and a grooved surface was measured under conditions that are typically used in grating orientation tasks. No evidence of anisotropy was found. Also, using a grating orientation task, separate estimates were made of sensitivity in the proximal-distal and lateral-medial orientations. Again no evidence of anisotropy was found. Consistent with changes in the density of innervation, grating orientation sensitivity was found to vary as a function of location on the fingerpad. The results support the view that grating orientation is a valid measure of spatial acuity reflecting underlying neural, spatial mechanisms.

Discrimination Learning↗
PubMed1999

Somesthesis.

In this review we focus on the perceptual and psychophysical aspects of somesthesis, although some information on neurophysiological aspects will be included as well; we look primarily at studies that have appeared since 1988. In the section on touch, we cover peripheral sensory mechanisms and several topics related to spatial and temporal pattern perception, specifically measures of spatial sensitivity, texture perception with particular emphasis on perceived roughness, complex spatial-temporal patterns, and the use of touch as a possible channel of communication. Other topics under this section include the effects of attention on processing tactile stimuli, cortical mechanisms, and the effects of aging on sensitivity. We also deal with thermal sensitivity and some aspects of haptics and kinesthesis. In the section on pain, we review work on the gate-control theory, sensory fibers, and higher neural organization. In addition, studies on central neurochemical effects and psychophysics of pain are examined.

Attention↗
PubMed1999

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on postoperative renal function: a meta-analysis.

The aim of this systematic review was to assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on post-operative renal function. Eight randomized placebo-controlled double-blinded trials (n = 345) were identified from searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register databases. The summary effect size and 95% confidence intervals (95% CI) were calculated by a weighted mean difference analysis using a random-effects model. The NSAIDs (diclofenac, ketorolac, indomethacin, ibuprofen) were used for up to three-days after surgery. There were no reported cases of postoperative renal failure requiring dialysis. NSAIDs reduced creatinine clearance by 22 ml.min-1 (95% CI: 7 to 37), sodium output by 54 mmol.day-1 (95% CI: 5 to 103) and potassium output by 38 mmol.day-1 (95% CI: 19 to 56) on Day 1 but not on Day 2. Serum creatinine increased on Day 2 by 15 mumol.l-1 (95% CI: 2 to 28). Urine volume did not change significantly at any time. There was therefore a clinically unimportant transient reduction in renal function. NSAIDs should not be withheld from patients with normal preoperative renal function because of concerns about postoperative renal impairment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible Splotch embryos.

The murine mutant Splotch (Sp) is a well-established model for studying neural tube closure defects. In the current investigation, the progression through neural tube closure (NTC) as well as the expression patterns of 12 developmentally regulated genes were examined in the neural tissue of wildtype (+/+), Splotch heterozygous (Sp/+), and Splotch homozygous (Sp/Sp) embryos during neurulation. The overall growth of the embryos, as measured by the number of somite pairs, did not differ significantly between the three genotypes at any of the collection time-points. There was, however, a significant delay in the progression through NTC for both the Sp/+ and Sp/Sp embryos. A univariate analysis on the expression of the 12 candidate genes (bcl-2, FBP-2, Hmx-2, Msx-3, N-cam, N-cad, noggin, p53, Pax-3, Shh, Wee-1, wnt-1) revealed that although 11 were statistically altered, across time or by genotype, there were no significant interactions between gestation age and genotype for any of these genes during NTC. However, a multivariate statistical analysis on the simultaneous expression of these genes revealed interactions at both gestation day (GD) 8:12 (day:hour) and 9:00 among Pax-3, N-cam, N-cad, bcl-2, p53, and Wee-1 that could potentially explain the aberrant NTC. The data from these studies suggest that a disruption in the genes that govern the cell cycle or extracellular matrices of the developing neural tube might play a critical role in the occurrence of the NTDs observed in Splotch embryos.

Animals↗
PubMed1998

Symptomatic urinary tract infection in preschool Australian children.

OBJECTIVE: To describe the demographic and clinical features, short-term outcomes, microbiology and renal tract abnormalities of a cohort of young Australian children with symptomatic urinary tract infection. METHODOLOGY: A total of 304 children < 5 years with their first documented symptomatic urinary tract infection who presented consecutively to the Emergency Department of a paediatric hospital between March 1993 and December 1994 and without a known predisposing cause were identified and details of their acute illness were recorded. Renal tract sonography, micturating cystourethrography and Tc-99 m dimercaptosuccinic acid scintigraphy (DMSA) were routinely performed. RESULTS: Of those who presented with urinary tract infection, 169 were boys and 135 girls; 64% were less than 1 year of age. For children from the local community, the cumulative incidence of urinary tract infection within the first 5 years of life was estimated to be 1.9% for boys and 1.8% for girls. There were no significant differences in illness characteristics according to mode of referral or geographical locality. Presenting symptoms were generally nonspecific and not referrable to the urinary tract. There were no deaths. One per cent of children required ventilatory support, and bacteraemia occurred in 6%, all of whom were under 6 months of age. E. coli was the causal organism in 84%, and a high in vitro resistance to ampicillin/ amoxycillin (54%) was demonstrated by the pathogens isolated. Bacteriuria was eradicated in 99% with antimicrobial treatment. In this setting, the sensitivities of dipstick urinalysis (leucocyte esterase+/-nitrites) and pyuria on microscopy (>10 x 10(6) white cells L(-1)) were 85%. Abnormal DMSA scintigraphy was detected in 39%, vesicoureteric reflux in 28%, and obstructive uropathy in 1%. CONCLUSIONS: This study provides current and local data on a large sample of children <5 years with urinary tract infection, which are useful to clinicians who manage children at risk of the condition.

Acute Disease↗
PubMed1998

Prevention of serious bacterial infection in children with nephrotic syndrome.

Although nephrotic syndrome is well known as a predisposing factor to bacterial infection in children, especially peritonitis due to Streptococcus pneumoniae, data on the incidence of infection and the effectiveness of preventative measures are limited. With particular reference to pneumococcal disease, this review summarises the available data on the pattern and incidence of invasive bacterial infection in children with nephrotic syndrome, and the level of evidence for the use of penicillin chemoprophylaxis and pneumococcal immunisation. Although data on the effectiveness of pneumococcal immunization in children with nephrotic syndrome are limited, the safety profile of this vaccine makes the risk-benefit ratio favourable to use of the current polysaccharide vaccine in those over 2 years of age. Conjugate pneumococcal vaccines are likely to be more effective, particularly in children under 2 years of age and should be available by the year 2000. Although penicillin prophylaxis against pneumococcal infection is not of proven benefit for nephrotic syndrome, it is beneficial in sickle cell disease without appreciable risk. Subgroups of patients with nephrotic syndrome most likely to benefit from twice daily phenoxymethyl penicillin prophylaxis include children under 2 years of age, with unresponsive or frequently relapsing disease, or who have had a previous episode of pneumococcal infection.

Antibiotic Prophylaxis↗
PubMed1998

Factors affecting tactile spatial acuity.

Tactile spatial acuity on the fingerpad was measured using a grating orientation task. In this task, subjects are required to identify the orientation of square-wave gratings placed on the skin. Previous studies have shown that performance varies as a function of the width of the grooves in the gratings. In the present study, both groove width and the overall size and configuration of the contactors were varied. Sensitivity improved with wider grooves and with larger contactors. Additional measurements showed that the improved sensitivity is not the result of the increase in total area contacted, but rather is due to two other factors associated with larger contactors. One is the greater linear extent of the larger contactors. The other appears to be due to the reduction in the interference produced by the outer edge of the contactor. Specifically, as the contactor increases in size, the distance between the outer edge and the center portion of the grooves also increases. It was also shown that subjects are more sensitive to a single, continuous groove as compared with two grooves of the same total length but spatially discontinuous. Similarly, subjects are more sensitive to a contactor with a continuous groove than to a contactor in which just the end points of the groove are presented. The results are generally consistent with the results of peripheral, neurophysiological recordings. The results are discussed in terms of the way in which both spatial and intensive factors may affect sensitivity to grating orientation.

Analysis of Variance↗
PubMed1998

Amplitude and period discrimination of haptic stimuli.

As part of a project to examine the ability of the hand to receive speech information, the present study examined subjects' ability to discriminate finger movements along the dimensions of amplitude and period (movement duration). The movements consisted of single-cycle, sinewave movements and single-cycle, cosine movements presented to the index finger. Difference thresholds were collected using an adaptive, two-interval, temporal forced-choice procedure. Amplitudes from 6 to 19 mm were examined, and the difference thresholds ranged from 10% to 18%. The thresholds were unaffected by the period of the movement. Periods from 3000 to 111 ms (0.33-9 Hz) were examined, and thresholds ranged from 6% to 16%. The thresholds were unaffected by the amplitude of the movement. Further measurements in which period was varied in the amplitude discrimination task and amplitude was varied in the period discrimination task indicated that subjects were not using peak velocity as the basis for discrimination. These measurements were collected using a display specifically designed for the examination of haptic stimulation and capable of presenting controlled patterns of movement and vibration to the fingers.

Differential Threshold↗
PubMed1998

Vibrotactile pattern isolation/integration.

Temporal integration has been cited as a major factor in temporal masking. Two experiments were designed to examine the conditions under which temporal integration may aid or hinder the perception of vibrotactile spatial patterns. In Experiment 1, the subject's task was to discriminate between pairs of patterns. Each pattern was composed of two temporally separated pattern elements. When the task required the subjects to perceive the individual pattern elements, performance improved with temporal isolation--that is, performance improved as the temporal separation between the elements increased. In a second task, when the discrimination could be based on either the overall pattern shape or the pattern elements, temporal integration appeared to improve performance--that is, performance improved as the temporal separation decreased. In Experiment 2, an identification task was used. Several factors appeared to determine whether temporal integration aided or hindered pattern identification. When pattern elements similar to those in Experiment 1 were tested, performance improved with increasing temporal separation (isolation). A single function was fit to the discrimination (isolation) and identification (isolation) results. Whether temporal integration aids or hinders pattern perception appears to depend on pattern shape, the pattern elements, and the nature of the task.

Female↗
PubMed1998

Variability in the interpretation of dimercaptosuccinic acid scintigraphy after urinary tract infection in children.

UNLABELLED: Technetium-99m-dimercaptosuccinic acid (DMSA) scintigraphy is a frequently used diagnostic test in pediatric practice to assess the presence and severity of renal damage. Most commonly it is performed after urinary tract infection. The aim of this study was to investigate the variability in the interpretation of DMSA scans by pediatric nuclear medicine physicians in this clinical setting. METHODS: We selected all 441 scans from children with first-time urinary tract infection who presented between 1993 and 1995 to a pediatric casualty department and who are participants in a prospective cohort study. Two hundred and ninety-four scans were performed at a median time of 7 days after diagnosis, and 147 scans were from children who were free from further infection over a 1-yr follow-up period. Two experienced nuclear medicine physicians independently interpreted the 441 scans according to whether renal damage was present or absent and using the modified 4-level grading system for DMSA abnormality of Goldraich. Apart from being informed that urinary tract infection was the indication for DMSA scintigraphy, no other clinical information was given to the nuclear medicine physicians. The indices of variability used were the percentage of agreement and the kappa statistic. For the grading scale used, both measures were weighted with integers representing the number of categories from perfect agreement. Disagreement was analyzed for children, kidneys and kidney zones. RESULTS: There was agreement in 86% (kappa = 69%) for the normal-abnormal DMSA scan dichotomy, and the weighted agreement was 94% (weighted kappa = 82%) for the grading of abnormality. Disagreement of DMSA scan interpretation of > or =2 grades was present in three cases (0.7%). The same high level of agreement was present for patient, kidney and kidney zone comparisons. Agreement was not influenced by age or timing of scintigraphy after urinary tract infection. CONCLUSION: Two experienced nuclear medicine physicians showed good agreement in the interpretation of DMSA scintigraphy in children after urinary tract infection and using the grading system of Goldraich.

Child↗
PubMed1997

Strain-dependent alterations in the expression of folate pathway genes following teratogenic exposure to valproic acid in a mouse model.

The molecular basis for the well-established hierarchy of susceptibility to valproic acid-induced neural tube defects in inbred mouse strains was examined using in situ transcription and anti-sense RNA amplification methodologies with both univariate and multivariate analyses of the resulting gene expression data. The highly sensitive SWV strain demonstrated a significant reduction in the expression of the folate binding protein (FBP-1) following the teratogenic insult at gestational day 8:18, while the more resistant LM/Bc embryos were up-regulating this gene in response to valproic acid treatment. More importantly, at all 3 gestational timepoints spanning the period of murine neural tube closure examined in this study, the LM/Bc embryos had significantly higher MTHFR (5,10-methylenetetrahydrofolate reductase) gene expression levels compared to the SWV embryos. As this folate pathway enzyme is important in homocysteine and methionine metabolism, it suggests that the SWV embryos may be hypomethylated, and essential gene expression during critical periods of neural tube closure is compromised by the teratogenic exposure to valproic acid. This study represents the first evidence of a strain difference in transcriptional activity in response to a teratogenic exposure that might be causally related to the development of the teratogen-induced congenital malformations.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗