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Biomedical subjects

J C Craig

Publications and source records attributed to J C Craig.

At least 91 records · Page 5Linked to original sources

Developmental expression of morphoregulatory genes in the mouse embryo: an analytical approach using a novel technology.

The molecular techniques of in situ transcription and antisense RNA amplification (IST/aRNA) have allowed for the monitoring of coordinate changes in the expression of multiple genes simultaneously. However, the analysis of their concurrent behavior during murine embryogenesis has been problematic. Studies involving the investigation of temporal and spatial gene expression during embryogenesis have focused solely on the analysis of isolated, single gene events. Such an approach has failed to provide an integrative picture of genetic control over the varied and complicated cellular processes governing embryogenesis. In order to interpret the enormous amount of gene expression data generated by these procedures, we have attempted to develop an analytical framework by employing the statistical concepts of principal components analysis (PCA). For the current study, we performed IST/aRNA on neural tubes dissected from the highly inbred LM/Bc murine strain collected during four gestational time periods. A subset of these genes, representing a partial signaling pathway in the developing neuroepithelium, was then subjected to PCA. Here, we report that PCA highlighted the transcriptional interplay among the genes p53, wee-1, Tgf beta-2, and bcl-2 such that the combined reciprocal regulation of their gene products is suggestive of a predominant proliferative state for the developing neuroepithelium. The application of PCA to the gene expression data has elucidated previously unknown interrelationships among cell cycle genes, growth, and transcription factors on a transcriptional level during critical stages of neurulation. The information gleaned from this analysis, while not definitive, suggests distinct hypotheses to guide future research.

Analysis of Variance↗

Effects of ethanol concentration and stripping temperature on continuous fermentation rate.

The operation of a pilot plant consisting of a 14-1 fermentor, 10-cm packed column and condenser for continuous fermentation and stripping of ethanol was stable for more than 100 days. The feed consisted of a non-sterile solution of 560 g/l glucose with 100 g/l corn steep water. Fouling of the packing in the column with attached growth of yeast cells was controlled by in situ washing at intervals of 3-6 days. A computer simulation of the pilot plant was developed and used to analyze the data. The productivity of the continuous fermentor varied from 14 g ethanol to 17 g ethanol l-1 h-1. The yield was equal to the maximum theoretically possible: 0.51 g ethanol/g glucose consumed. Results are fit to linear models for the effects of ethanol concentration on specific growth rate and cell yield, and for the effect of stripping temperature on specific growth rate.

Ethanol↗

Variation in the diagnosis of vesicoureteric reflux using micturating cystourethrography.

Variability in the interpretation of micturating cystourethrography by paediatric radiologists for the diagnosis of vesicoureteric reflux in children was evaluated. All 265 micturating cystourethrograms (MCUs) that were available from 304 consecutive children aged 0.5-61 months-who were investigated after their first urine infection between 1993 and 1995 as part of a prospective cohort study-were selected for interpretation. Three experienced paediatric radiologists from the same department independently interpreted the MCUs according to the grading system of the International Reflux Study in Children, from grades 0 to V, with the presence of intrarenal reflux also noted. Apart from being informed that urine infection was the indication for the MCU, no other clinical information was given to the radiologists. The indices of variability used were the percentage of agreement and the kappa statistic, expressed as a percentage. Both measures were weighted with integers representing the number of categories from perfect agreement. Disagreement was analysed for children and kidneys. For the diagnosis of vesicoureteric reflux in individual patients, including grade, the percentage of agreement was 96%-97% (kappa 90%-91%) and the weighted percentage of agreement was 96%-98% (weighted kappa 93%-94%). The same high level of agreement was present for individual kidneys, with a percentage of agreement of 97%-98% (kappa 89%-92%) and a weighted percentage of agreement of 98%-99% (kappa 94%-95%). There was near perfect agreement in the interpretation of radiological micturating cystourethrography among three experienced paediatric radiologists for the diagnosis and grade of vesicoureteric reflux. Any variations in the medical care of children suspected of having vesicoureteric reflux are not explained by differences in the reporting of this diagnostic test.

Child↗

Trends in the health burden due to urinary tract infection in children in Australia.

OBJECTIVE: To estimate the health burden of urinary tract infection in children less than 15 years of age in Australia and to ascertain whether any significant change has occurred during the past decade. METHODOLOGY: The number of children less than 15 years of age who were admitted in New South Wales for urinary tract infection between 1981 and 1994 was ascertained from the Department of Health, and age and sex specific incidence rates were calculated using Australian Bureau of Statistics population data. Costs for inpatient care were calculated using the cost weights from Australia National Disease Related Groups Version 3 for urinary tract infection (DRG 577). The frequency of the four most commonly requested renal tract imaging procedures in children following urinary tract infection and which qualified for Medicare reimbursement were obtained from the Health Insurance Commission for 1984-1994: micturating cystourethrography, intravenous urography, renal ultrasonography, and nuclear medicine renal studies. RESULTS: There were 1203 children who were admitted with urinary tract infection in New South Wales in 1994, at an estimated cost of $A1.6 million. Since 1981, the age standardized annual incidence of urinary tract infection requiring hospitalization has increased from 0.5 to 0.9 per 1000 children, largely because of an increase in the number of young children admitted (from 0.6 to 2.0 per 1000 children less than 5 years of age). In 1994, 46,230 non-inpatient renal imaging procedures were undertaken in children under 15 years of age at a cost of $A5.3 million. CONCLUSIONS: Urinary tract infection is an important and increasing health problem for Australian children, particularly for preschool children. Whether this represents a true increase in the incidence of urinary tract infection or improved diagnosis and more intensive management is not possible to establish with this study design. Prospective population based studies are required to assess more completely the frequency with which urinary tract infection occurs in children and any changes that may be occurring.

Adolescent↗

Vesicoureteric reflux and timing of micturating cystourethrography after urinary tract infection.

OBJECTIVE: To test the medical belief that the micturating cystourethrogram (MCU) be deferred four to six weeks after acute symptomatic urinary tract infection (UTI) because of the risk of falsely detecting vesicoureteric reflux if performed earlier. STUDY DESIGN: A cross sectional analytic study of preschool children with first time symptomatic UTI. RESULTS: Of the 284 eligible children, 272 (95.8%) had MCU at a median time of 29 days after diagnosis (range 5 to 167 days). Vesicoureteric reflux was present in 77 children (28.3%). Beyond one week after diagnosis (270 children) the proportion and severity of vesicoureteric reflux detected was not associated with the timing of the MCU. Before one week, both children tested had vesicoureteric reflux. CONCLUSIONS: The presence and grade of vesicoureteric reflux is not influenced by the timing of the MCU one week after acute symptomatic UTI. There may be an association between the MCU and the presence of vesicoureteric reflux for children tested within one week after UTI. The MCU need not be deferred for four to six weeks after UTI.

Child, Preschool↗

Tactile pattern perception by two fingers: temporal interference and response competition.

The identification of a spatial pattern (target) presented to one fingerpad may be interfered with by the presentation of a second pattern (nontarget) to either the same fingerpad or a second fingerpad. A portion of the interference appears to be due to masking and a portion to response competition. In the present study, vibrotactile spatial patterns were designed to extend over two fingerpads. Target and nontarget patterns were presented to the same two fingerpads with a temporal separation between the two patterns. The function relating target identification to the temporal separation between the target and nontarget was very similar to the functions obtained with one-finger patterns in temporal masking studies. Subsequent measurements showed that a substantial portion of the interference resulted from response competition. Pattern categorization was better when patterns were presented to two fingers on opposite hands than to two fingers on the same hand; however, there was more interference for patterns presented bilaterally than for patterns presented ipsilaterally. The results supported the conclusion that similar processes are involved in the perception of sequences of spatial patterns whether the patterns are presented to one or to two fingers.

Adult↗

Communication breakdown: a preventable cause of acute renal failure in a newborn infant.

A three-week-old boy had life-threatening renal failure which was successfully treated by salbutamol and sodium bicarbonate infusion, rectal resonium and a left percutaneous nephrostomy. Ultrasonography of this child at 19 weeks' gestation had shown a treatable renal tract abnormality (bilateral hydronephrosis). No arrangements had been made for follow-up.

Acute Kidney Injury↗

Valproic acid-induced changes in gene expression during neurulation in a mouse model.

The teratogenic potential of valproic acid has been well established both in experimental models and in human clinical studies. As with all human teratogens, there are genetically determined differences in individual susceptibility to the induction of congenital defects. Using a mouse model of valproate-induced neural tube defects, a study was undertaken to examine differential changes in gene expression for selected transcription factor (Pax-3, Emx-1, Emx-2, c-fos, c-jun, creb) and cell cycle checkpoint genes (bcl-2, p53, wee-1) during neural tube closure. In general, exposure to teratogenic concentrations of valproic acid elicited GD 9:12 control levels of transcription factor mRNA expression in GD 9:0 embryos of both strains. This accelerated developmental profile is marked by significant elevation of Emx-1, Emx-2, c-fos, c-jun, and creb expression. There was also a significant over expression of the cell cycle genes p53 and bcl-2 in the LM/Bc embryos in response to the teratogenic insult. Examination of the ratio of expression of these genes clearly favored bcl-2, which supports the hypothesis that altered neuroepithelial cell proliferation rates, rather than increased apoptosis, is the underlying mechanism by which valproic acid alters normal neural tube morphogenesis. An investigation into interactive effects of these genes on the molecular profile of GD 9:0 embryos further validated this observation. That is, the overall proliferative state among the control embryos was prematurely modified into a more differentiated state following teratogenic insult. These results suggest that alterations in the expression of multiple genes are most likely responsible for valproic acid-induced neural tube defects.

Animals↗

Arsenic-induced alterations in embryonic transcription factor gene expression: implications for abnormal neural development.

We examined the morphological and molecular consequences of acute in utero exposure to teratogenic concentrations of arsenate. The treatment produced a dose-related increase in neural tube defects, along with a significant alteration in the pattern of gene expression for several transcription factors (creb, Hox 3.1, Pax3, and Emx-1) that were examined using in situ transcription and antisense RNA amplification procedures. On gestational day 9:0, there was a significant delay in the embryos progression through neural tube closure, accompanied by a significant downregulation of Hox 3.1 expression and a significant upregulation of Pax3, Emx-1, and creb. As both Hox 3.1 and Pax3 serve to regulate N-CAM expression, it is possible that abnormalities associated with N-CAM may compromise neural crest cell migration and normal neural tube closure.

Animals↗

Effect of circumcision on incidence of urinary tract infection in preschool boys.

OBJECTIVE: To determine whether circumcision decreases the risk of symptomatic urinary tract infection (UTI) in boys less than 5 years of age. STUDY DESIGN: A case-control study (1993 to 1995) in the setting of a large ambulatory pediatric service. Case subjects and control subjects were drawn from the same population. One hundred forty-four boys less than 5 years of age (median age, 5.8 months) who had a microbiologically proven symptomatic UTI (case subjects), were compared with 742 boys (median age, 21.0 months) who did not have a UTI (control subjects). The proportion of case and control subjects who were circumcised in each group was compared with the use of the chi-square test, with the strength of association between circumcision and UTI expressed in terms of an odds ratio. To determine whether age was a confounder or an effect-modifier, we stratified the groups by age (< 1 year; > or = 1 year) and analyzed by the method of Mantel-Haenszel. RESULTS: Of the 144 preschool boys with UTI, 2 (1.4%) were circumcised, compared with 47 (6.3%) of the 742 control subjects (chi-square value = 5.6; p = 0.02; odds ratio, 0.21; 95% confidence intervals, 0.06 to 0.76). There was no evidence that age was a confounder or modified the protective effect of circumcision on the development of UTI (Mantel-Haenszel chi-square value = 6.0; p = 0.01; combined odds ratio, 0.18; 95% confidence intervals, 0.05 to 0.71; Breslow-Day test of homogeneity chi-square value = 0.6; p = 0.4). CONCLUSIONS: Circumcision decreases the risk of symptomatic UTI in preschool boys. The protective effect is independent of age.

Age Distribution↗

Interference in identifying tactile patterns: response competition and temporal integration.

When two vibrotactile spatial patterns-one target and one nontarget pattern-are presented to the same location, subjects may have difficulty in identifying the target pattern. The difficulty may be in part the result of the target's and nontarget's being processed to the point of evoking competing responses. Subjects err by responding with the nontarget. Target identification may also be interfered with because the target and nontarget form a composite pattern through temporal integration, and subjects are unable to separate the features of the target and nontarget patterns. The present study addressed the issue of whether a response competition explanation of interference is consistent with the existence of temporal integration and the formation of composite patterns. A series of three experiments examined temporal integration and its relationship to response competition. The results indicate that both temporal integration and response competition can occur under similar stimulus conditions, and that both can interfere with the identification of target patterns. The results further indicate that even under conditions in which composite patterns are formed, the two patterns that constitute the composite are still identifiable. It is concluded that the interference in pattern identification attributed to response competition is not a result of temporal integration.

Adult↗

Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959.

A human immunodeficiency virus type 1 (HIV-1) variant with highly reduced susceptibility to Ro 31-8959, an inhibitor of the viral proteinase, has been selected by repeated passage of wild-type virus in CEM cells in the presence of increasing concentrations of the inhibitor. Peptide sequences of the proteinase of selected virus were obtained from proviral DNA. Sequence comparison to wild-type (wt) proteinase demonstrated two amino acid substitutions in the resistant virus, a Gly to Val exchange at position 48 and a Leu to Met exchange at position 90. Furthermore, sequences of intermediate passage virus suggest contributions from positions 12, 36, 57, and 63 in early steps of resistance development. The selected virus showed a ca. 40-fold increase in 50% inhibitory concentration of Ro 31-8959. Growth kinetics of resistant virus were comparable to wild-type virus and the resistant genotype proved to be stable in the absence of inhibitor. Directed mutagenesis of the HIV-1 HXB2 proteinase at positions 48 and 90 suggested that each mutation alone led to a moderate decrease in sensitivity of the recombinant virus to proteinase inhibitor. However, a recombinant virus carrying both mutations in the proteinase gene showed a significant reduction in its sensitivity to Ro 31-8959 thus proving the importance of these exchanges for the resistance phenotype.

Amino Acid Sequence↗

Preparation of casein using carbon dioxide.

The effects of pressure, temperature, residence time, and mass of skim milk on some characteristics of casein, prepared by precipitation with high pressure CO2, were examined in a batch reactor. For a 500-g milk sample, precipitation occurred at pressures > 2760 kPa and temperatures > 32 degrees C. Residence time was not significant and was held at 5 min. Yields were maximum at 2750 to 5520 kPa and at 38 to 49 degrees C for a 500-g milk sample. The resulting whey had a pH of 6.0. The casein product had an acceptable appearance and had greater solids, ash, and Ca contents than commercial acid caseins. Particle size distribution studies showed that the mean particle size was sensitive to precipitation pressure and temperature and was similar to that of acid caseins produced under laboratory conditions. The HPLC studies of the casein and whey fractions showed that precipitation by CO2 did not result in fractionation of casein or whey proteins to their component proteins.

Animals↗

Vibrotactile masking: the role of response competition.

When two tactile patterns, a target and a nontarget pattern, are presented in close temporal proximity to the same location, the nontarget pattern may interfere with the identification of the target. A series of experiments examined the extent to which the interference in target identification results from masking (interference in the representation of the target at an early stage of processing) or from response competition. A response competition view of pattern perception holds that both the target and nontarget are fully processed to the level of evoking responses. Interference is produced when subjects select the nontarget rather than the target. This view was tested with a paradigm developed in studies of selective attention. Pairs of tactile patterns were presented to subjects' left index fingerpads. The amount of interference produced by a nontarget that is physically different from a target depends on whether the nontarget is associated with the same response as the target or a different response. The amount of masking also depends on the set of target and nontarget patterns that are used. The results support the conclusion that subjects have available a representation of both the target and the nontarget and that a substantial portion of the interference previously attributed to masking may be due to response competition.

Adult↗

Tactile selective attention and temporal masking.

The presentation of a nontarget stimulus to one fingerpad interferes with the identification of a target stimulus presented to a second fingerpad. This interference has been attributed to a failure of selective attention and, more specifically, to the nontarget's eliciting a competing response. In the present study, the temporal interval between the target and nontarget was varied to determine the extent to which a nontarget primes a competing response. The results showed more interference when the nontarget was presented after the target than when it was presented before the target. Although still consistent with a response-competition explanation, this result offered no support for a priming explanation. The function relating the amount of interference to the temporal separation between the target and nontarget was similar to the functions obtained in studies of temporal masking, and this prompted a second experiment in which temporal masking was examined. These results, obtained with stimuli presented to the same fingerpad, indicate that response competition may be a major factor in temporal masking and that similar processes are involved in temporal masking and selective attention.

Adult↗

Phosphate enema poisoning in children.

OBJECTIVE: To report a case of hypocalcaemic tetany occurring in a child secondary to two phosphate enemas administered for faecal retention, and review the literature of phosphate enema toxicity in children. CLINICAL FEATURES: A 23-month-old child with a repaired anorectal malformation and associated unilateral renal hypodysplasia presented with hypocalcaemic tetany (minimum serum calcium level, 1.11 mmol/L), hyperphosphataemia (maximum serum phosphate level, 6.06 mmol/L), hypokalaemia (minimum serum potassium level, 1.9 mmol/L) and dehydration 10 hours after the administration of two phosphate enemas for acute on chronic faecal retention. MANAGEMENT AND OUTCOME: Management consisted of parenteral rehydration, potassium supplementation, calcium gluconate, an enterally administered phosphate binder and saline bowel washouts to evacuate the remaining enema. She was discharged on day eight, with normal biochemical parameters and no neurological sequelae. CONCLUSION: The use of phosphate enemas in children under five years of age is associated with significant morbidity due to hyperphosphataemia, hypocalcaemia, hypokalaemia and dehydration. They should not be used in children under two years of age, and should be used only with extreme caution in children aged two to five years, especially in those with underlying bowel or renal dysfunction.

Child↗

Metabolites of chloroquine: some observations on desethylchloroquine and N-acetyldesethylchloroquine.

The major metabolite of chloroquine, (+)-desethylchloroquine, produced by stereoselective N-dealkylation of the drug, was obtained in 81.5% enantiomeric purity by resolution of racemic desethylchloroquine using an atropisomeric resolving agent and was shown by circular dichroism to have the absolute (S)-configuration. The minor metabolite N-acetyldesethylchloroquine was prepared in both the racemic and the (S)-(+)-form.

Acetylation↗