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Biomedical subjects

J E Coleman

Publications and source records attributed to J E Coleman.

At least 19 recordsLinked to original sources
PubMed2001

Pinopsin mRNA levels are significantly elevated in the pineal glands of chickens carrying a null mutation in guanylate cyclase-1.

The purpose of this study was to determine if the absence of guanylate cyclase-1 (RetGC1, GC1), a key visual phototransduction cascade enzyme that is expressed in both retinal photoreceptors and pinealocytes, disrupts light regulation of pinopsin mRNA levels in the chicken pineal gland. In this series of experiments, we compared levels of pinopsin and tryptophan 5-hydroxylase mRNA in the pineal glands of GUCY1*B (*B) and normal chickens housed under either cyclic light or constant dark conditions. The *B chicken carries a null mutation in the gene encoding guanylate cyclase-1 that results in blindness in these animals at hatching. The results of our experiments show (1) that the amount of pinopsin mRNA in *B pineal is significantly higher than the amount in normal pineal in both light and dark conditions, (2) that light induces an increase in pinopsin mRNA levels in *B pineal, (3) that the relative magnitude of the light-induced increase in pinopsin mRNA in *B pineal is not significantly different from that observed in normal pineal, and (4) that the changes in the regulation of pinopsin mRNA levels in *B pineal gland are not accompanied by changes in the circadian expression of tryptophan 5-hydroxylase mRNA. These results show that the absence of guanylate cyclase-1 expression in the *B pineal gland leads to a significant increase in basal levels of pinopsin mRNA in this gland but does not alter the magnitude of the increase in pinopsin mRNA levels that is observed as a result of light stimulation.

Animals↗
PubMed2001

Do gastrostomies close spontaneously? A review of the fate of gastrostomies following successful renal transplantation in children.

Previous published data have shown the benefit of nutritional support delivered via a gastrostomy button (GB) for children on chronic dialysis. The use of the GB is suspended following renal transplantation (RT) in most children and it is usually removed 2-3 months later together with the chronic dialysis catheter when the child is on alternate-day steroids. We reviewed the outcome of gastrostomies following successful RT in children. The gastrostomies were created by an open technique (Stamm) with the child under general anaesthesia, usually at the time of insertion of a chronic dialysis catheter. Growth data and complications of the GB were collected in a prospective registry. Following RT, the GB was removed with the expectation that the tract would close spontaneously. Those in whom a gastrocutaneous fistula persisted underwent formal surgical closure. A total of 18 children have had gastrostomy buttons removed: 11 gastrostomies (61%) closed spontaneously, but 7 (39%) required operative closure at a median of 2 months (range 3 weeks-4 years) post-removal. The need for formal closure was significantly related to the duration that the gastrostomy had been in situ pre-transplant (non-parametric statistics, 0.05 > p > 0.01). Although nearly two-thirds of gastrostomies in this study closed spontaneously following RT, less than one-half of those that had been in situ for more than 1 year did so. We thus recommend formal closure of all gastrostomies that have been in situ for more than 1 year. This can be done at the same operation as the removal of the chronic dialysis catheter.

Adolescent↗
PubMed2000

Effect of estrogen on cerebral glucose metabolism in postmenopausal women.

PET was used to evaluate the effect of estrogen use on regional cerebral glucose metabolism in postmenopausal women. Women receiving estrogen replacement therapy (ERT+), women not receiving estrogen (ERT-), and women with AD were studied. The ERT- group showed metabolic ratios that were intermediate to the ERT+ and AD groups, although they did not show any signs of cognitive impairment. These findings show an effect of estrogen depletion on brain metabolic activity.

Aged↗
PubMed2000

Gastrostomy buttons for nutritional support in children with cystinosis.

Poor growth in children with cystinosis may be a combination of sub-optimal nutritional intake, gastrointestinal dysfunction and polypharmacy. We report our experience with gastrostomy buttons (GBs) in five children (4 male) with cystinosis treated at a median age of 3 years (range 1.4-8.8 years). All children received overnight GB feeding for a mean duration of 27 months (range 7-42 months). During 135 patient-months of observation, the mean life of the GB was 5.7 months (range 3-7.7 months), with a mean of 3.4 GB changes (range 1-6) per patient. An average of five (range 3-7) medications were administered daily via the button. The mean energy intake achieved was 118% of the estimated average requirement (range 86%-183%), with 58% of total energy and 55% of protein intake being delivered via the GB during the study period. Mean height standard deviation score (SDS) was -3.79 at the start of GB feeding and -3.08 at the end of the study period, with mean weight SDS of -3.79 and -2.17 (P=0.042), respectively. The buttons have been welcomed by the families and should be considered as a treatment option for providing the nutritional prescription and administering medications.

Child↗
PubMed2000

Nutrition and growth in relation to severity of renal disease in children.

Practical joint medical/dietetic guidelines are required for children with chronic renal insufficiency (CRI). Nutritional status and growth were compared in 95 children (59 male) > 2 years age with CRI, grouped following [51Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min/1.73 m2) estimations into 'normal' kidney function [GFR > 75 (mean 104 (SD 18.9), n = 35], mild (GFR 51-75, n = 23), moderate (GFR 25-50, n = 19) and severe CRI (GFR < 25, n = 18). Anthropometry [weight (wt.), height (ht.), and body mass index (BMI)], laboratory investigations and a 3-day dietary record were obtained. All anthropometric indices deteriorated with worsening renal function, from mean SD scores for wt., ht. and BMI in 'normal' children of 0.32 (SD 1.2), 0.4 (SD 1.0) and 0.1 (SD 1.3), respectively, to values of -1.28 (SD 1.1; P < 0.001), -1.52 (SD 1.1; P < 0.001) and -0.42 (SD 1.1; NS) in severe CRI. Mean total energy intake decreased from 103% (SD 17) estimated average requirement (EAR) in 'normal' children to 85% EAR (SD 27; P = 0.004) in severe CRI. Mean serum PTH concentrations (normal laboratory range 12-72 ng/l) were higher in moderate [67 ng/l (SD 58), P < 0.001] and severe CRI [164 ng/l (SD 164), P < 0.001] and mean serum phosphate concentrations were higher in severe CRI (1.54 mmol/l (SD 0.17), P = 0.009) compared to 'normal'. Disturbances in nutritional intakes, bone biochemistry and growth occur early in CRI and suggest the need for joint medical/dietetic intervention in children with mild and moderate CRI, in addition to those with more severe CRI.

Adolescent↗
PubMed1999

The RING finger motif of photomorphogenic repressor COP1 specifically interacts with the RING-H2 motif of a novel Arabidopsis protein.

The constitutive photomorphogenic 1 (COP1) protein of Arabidopsis functions as a molecular switch for the seedling developmental fates: photomorphogenesis under light conditions and skotomorphogenesis in darkness. The COP1 protein contains a cysteine-rich zinc-binding RING finger motif found in diverse groups of regulatory proteins. To understand the role of the COP1 RING finger in mediating protein-protein interaction, we have performed a yeast two-hybrid screen and isolated a novel protein with a RING-H2 motif, a variant type of the RING finger. This protein, designated COP1 Interacting Protein 8 (CIP8), is encoded by a single copy gene and localized to cytosol in a transient assay. In addition to the RING-H2 motif, the predicted protein has a C4 zinc finger, an acidic region, a glycine-rich cluster, and a serine-rich cluster. The COP1 RING finger and the CIP8 RING-H2 domains are sufficient for their interaction with each other both in vitro and in yeast, whereas neither motif displayed significant self-association. Moreover, site-directed mutagenesis studies demonstrated that the expected zinc-binding ligands of the RING finger and RING-H2 fingers are essential for their interaction. Our findings indicate that the RING finger motif, in this case, serves as autonomous protein-protein interaction domain. The allele specific effect of cop1 mutations on the CIP8 protein accumulation in seedlings indicates that its stability in vivo is dependent on the COP1 protein.

Amino Acid Sequence↗
PubMed1999

A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2.

RAG1 and RAG2 are the two lymphoid-specific proteins required for the cleavage of DNA sequences known as the recombination signal sequences (RSSs) flanking V, D or J regions of the antigen-binding genes. Previous studies have shown that RAG1 alone is capable of binding to the RSS, whereas RAG2 only binds as a RAG1/RAG2 complex. We have expressed recombinant core RAG1 (amino acids 384-1008) in Escherichia coli and demonstrated catalytic activity when combined with RAG2. This protein was then used to determine its oligomeric forms and the dissociation constant of binding to the RSS. Electrophoretic mobility shift assays show that up to three oligomeric complexes of core RAG1 form with a single RSS. Core RAG1 was found to exist as a dimer both when free in solution and as the minimal species bound to the RSS. Competition assays show that RAG1 recognizes both the conserved nonamer and heptamer sequences of the RSS. Zinc analysis shows the core to contain two zinc ions. The purified RAG1 protein overexpressed in E.coli exhibited the expected cleavage activity when combined with RAG2 purified from transfected 293T cells. The high mobility group protein HMG2 is stably incorporated into the recombinant RAG1/RSS complex and can increase the affinity of RAG1 for the RSS in the absence of RAG2.

Animals↗
PubMed1999

Provision of dietetic care in children on chronic peritoneal dialysis.

OBJECTIVE: To estimate the provision of dietetic care necessary to manage and support children receiving chronic peritoneal dialysis (CPD) with/without nutritional support via a gastrostomy button (GB) and their families. DESIGN: Three-year prospective, longitudinal study documenting dietetic contacts (direct: inpatient/outpatient, telephone, home, school, and family practitioner visits; and indirect: with other health professionals). SETTING: Regional Pediatric Renal Unit. PARTICIPANTS: Thirteen children (7 male; 5 <5 yrs of age) commenced CPD at a mean age of 7.7 years (range, 0.2 to 8.5 years). Eight children received tube feeding (7 GB, 1 nasogastric [NG]) in combination with CPD at a mean age of 4.3 years (range, 0.2 to 8.2 years). MAIN OUTCOME MEASURES: Quantitative data regarding dietetic contacts and growth parameters. RESULTS: Seven hundred eighty-one dietetic contacts were recorded during 182 patient months of observation, with a mean of 5.9 (standard deviation [SD] 1.9) contacts per patient, per month in children <5 years of age, compared with 3.1 (SD 1.6) contacts in children >5 years of age. Eighty-two percent of contacts were with children receiving nutritional support via a GB. Telephone contact accounted for 41% of all contacts in the less than 5 years of age group, compared with 7% in children greater than 5 years of age. Mean standard deviation scores (SDS) for height and weight at the start of the study were -1.2 and -1.32, and at the end were -1.14 and -0. 73. Body mass index (BMI) SDS significantly improved from -0.91 to 0. 17 (P = 0.03). CONCLUSION: This study illustrates the number and nature of dietetic contacts that we felt were required to support children and families on CPD. Attempts to achieve adequate nutritional intakes for growth require frequent adjustments of nutritional prescriptions, particularly in preschool children.

Adolescent↗
PubMed1999

Short communication: the N-terminal fragment of Arabidopsis photomorphogenic repressor COP1 maintains partial function and acts in a concentration-dependent manner.

Arabidopsis seedlings exhibit distinct developmental patterns according to their light environment: photomorphogenesis in the light and etiolation or skotomorphogenesis in darkness. COP1 acts within the nucleus to repress photomorphogenesis in darkness, while light depletes COP1 from nucleus and abrogates this repression. COP1 contains three structural modules: a RING finger followed by a coiled-coil domain, and a WD40 repeat domain at the C-terminus. By introducing various domain deletion mutants of COP1 into cop1 null mutant backgrounds, we show that all three domains are essential for the function of COP1 in vivo. Interestingly, a fragment containing the N-terminal 282 amino acids of COP1 (N282) with both the RING finger and coiled-coil modules is sufficient to rescue the lethality of the cop1 null mutations at low expression level. However, high expression levels of the N282 fragment result in a phenocopy of the cop1 null mutation. The sensitivity of the seedling to levels of N282 could reflect the importance of the abundance of COP1 for the appropriate regulation of photomorphogenic development.

Arabidopsis↗
PubMed1998

Zinc enzymes.

The number of zinc enzymes for which detailed structural and mechanistic data, including high resolution crystal structures, are available is increasing rapidly. The new findings continue to support the conclusion that the majority of zinc enzymes catalyze hydrolysis or closely related transfer reactions. In a protein environment, tetrahedral or 5-coordinate Zn2+ is ideally suited to activate a coordinated water (frequently a Zn2+--OH) as a nucleophile attacking the carbonyl carbon of a peptide bond, the carbon of carbon dioxide or the phosphorus of a phosphate ester. Protein-bound Zn2+ can function catalytically by forming mixed complexes with the substrate, either by expanding its coordination sphere or by exchanging a ligand. Formation of protein-Zn2+-substrate bonds can position the substrate or polarize its electron distribution to facilitate further steps in the reaction.

Alkaline Phosphatase↗
PubMed1998

Gastrostomy buttons for nutritional support on chronic dialysis.

RATIONALE: Nutritional support for children on chronic dialysis often involves the use of nasogastric tubes or gastrostomy feeding. We report our experience using gastrostomy buttons (GB) over a 6.6-year period to document their success/failure, the feeding regimens employed and the impact on growth. DESIGN: In 339 patient months of prospective observation, 22 children (14 male) commenced gastrostomy feeding at a median age of 2.3 years (range 0.2-10.3 years). Sixteen patients had an initial gastrostomy catheter inserted at the same time as a chronic dialysis catheter. Eighteen patients were established on continuous cycling peritoneal dialysis (CCPD) and four on haemodialysis (HD). RESULTS: The mean duration of combined gastrostomy feeding and chronic dialysis was 14.5 months (range 2.4 56 months). In 20 of the children followed for 6 months on combined GB feeding and dialysis, the mean protein and energy intakes were 2.5 g/kg bodyweight/day (range 1.7-3.4 g) and 108 kcal/kg bodyweight/day (range 72-129 kcal). The mean energy intake achieved was 116% (range 98-155%) of the estimated average requirement (EAR) for energy. The mean percentage of total energy and protein intakes delivered via the GB during the study period was 61% (33-95%) and 61% (23-98%) respectively. Mean height standard deviation score (SDS) was -2.22 prior to GB feeding and -2.06 at the end of the study period (P = 0.005) and mean weight SDS was -2.22 and -1.16 (P = 0.001) respectively. The mean life of the GB was 7.7 months (range 2.6 14 months) with most button changes due to leakage problems. Two episodes of peritonitis were attributable to the GB with one requiring peritoneal dialysis catheter removal due to candida infection. The GB was removed at a mean of 2.8 months (range 0.8-8.3 months) after renal transplantation in 13 children. CONCLUSION: The gastrostomy button provides a valuable and aesthetically appealing route for nutritional support with few complications.

Anthropometry↗
PubMed1998

Growth posttransplantation in children previously treated with chronic dialysis and gastrostomy feeding.

Nasogastric and gastrostomy feeding are beneficial in providing nutritional support to children on chronic dialysis, but concerns have been raised about transfer to exclusive oral nutrition postrenal transplantation (TX). The present study reports the growth data and feeding outcomes in 14 children (9 male) who received combined dialysis [continuous cycling peritoneal dialysis (CCPD): n = 12; hemodialysis (HD): n = 2] and gastrostomy button (GB) feeding for a mean duration of 15.6 months, and who were transplanted at a mean age of 5.4 years. In 12 patients GB feeding was discontinued shortly after TX, and in 2 it was maintained for 3 and 8 months, respectively. No infective episodes were attributable to the GB post-TX, and the buttons were usually removed within 3 months with the dialysis catheter. The mean height and weight standard deviation scores (SDS) were -2.44 and -2.29, respectively, prior to dialysis and GB feeding; -2.19 and -1.22, respectively, prior to TX; and had improved to -1.6 and -0.79, respectively, 12 months post-TX. The mean percentage weight-for-height at the time of TX was 105% (range: 86%-128%), and was unchanged 1 year post-TX. We conclude that GB feeding in this group of children resulted in few complications or feeding problems post-TX. The use of GB feeding without growth hormone maintained growth parameters in most children while on dialysis, and a significant improvement in growth occurred after the renal transplantation.

Anthropometry↗
PubMed1997

Initiation, elongation, and processivity of carboxyl-terminal mutants of T7 RNA polymerase.

Bacteriophage T7 RNA polymerase is a single-subunit enzyme which has a C-terminal amino acid sequence of Phe-Ala-Phe-Ala883 (FAFA883). Closely related hydrophobic sequences are present at the C termini of seven other single-subunit RNA polymerases, including the mitochondrial RNA polymerase. Mutations at any of the four C-terminal residues depress initiation rates of T7 RNA polymerase from 50 to 95%, accompanied by large increases in the K(m) values for the initiating nucleotide, GTP, as well as the K(m)'s for promoter DNA. The dramatic drops in initiation rates shown by the mutant enzymes remain after correcting for any alteration in saturation of the enzyme by the initiating nucleotide or the promoter DNA resulting from the changes in K(m). In contrast, the high processivity of the enzyme is not altered by mutations in the last four residues. However, the propensity for the enzyme to add an untemplated nucleotide at the 3'-ends of transcripts is abolished by the A880AFA883 mutation. The C-terminal FAFA sequence or foot appears to interact both with the initiating NTP and with the most downstream nucleotides of the promoter, possibly through hydrophobic interactions with the minor groove, in the region where free radical footprinting of the polymerase-promoter DNA complex suggests that the enzyme binds across the minor groove.

Bacteriophage T7↗
PubMed1997

Cytotoxic peptides hemiasterlin, hemiasterlin A and hemiasterlin B induce mitotic arrest and abnormal spindle formation.

PURPOSE: Hemiasterlin, hemiasterlin A and hemiasterlin B are newly isolated cytotoxic tripeptides with potential as antitumor drugs. We wished to determine their mechanism of cytotoxicity. METHODS: We studied their effect on cell survival, cell cycle progression, and microtubule morphology in MCF-7 human mammary carcinoma cells. RESULTS: At the nanomolar concentrations at which they were cytotoxic, the peptides induced arrest in mitotic metaphase. Hemiasterlin A produced abnormal mitotic spindles like those produced by the microtubule inhibitors taxol, nocodazole and vinblastine at low concentrations. At high concentrations hemiasterlin A did not cause microtubule bundling like taxol, but caused microtubule depolymerization like nocodazole and vinblastine. CONCLUSIONS: The hemiasterlins probably exert their cytotoxic effect by inhibiting spindle microtubule dynamics.

Animals↗
PubMed1997

Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster.

The crystal structure of the dimerization domain of the V(D)J recombination-activating protein, RAG1, was solved using zinc anomalous scattering. The structure reveals an unusual combination of multi-class zinc-binding motifs, including a zinc RING finger and a C2H2 zinc finger, that together from a single structural domain. The domain also contains a unique zinc binuclear cluster in place of a normally mononuclear zinc site in the RING finger. Together, four zinc ions help organize the entire domain, including the two helices that form the dimer interface.

Binding Sites↗