PubMed Health⌕ Search

Biomedical subjects

D E Carey

Publications and source records attributed to D E Carey.

At least 19 recordsLinked to original sources
PubMed2003

The coxsackievirus and adenovirus receptor acts as a tumour suppressor in malignant glioma cells.

The coxsackievirus and adenovirus receptor (CAR) is a membrane glycoprotein with a cytoplasmic domain, a transmembrane domain and an extracellular region consisting of two immunoglobulin-like domains, an amino-terminal immunoglobulin variable (IgV)-related domain (D1), which is distal to the cell surface, and a proximal IgC2 domain (D2). The coxsackievirus and adenovirus receptor has been shown to exhibit tumour suppression activity in human bladder and prostate cancer cells. In the current paper, we demonstrate that CAR is a tumour suppressor in glioma cells and that the extracellular D2 domain is not required for this inhibitory effect. This finding provides a biological basis for the observation that expression of CAR is downregulated in malignant glioma cells. This suggests that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors for cancer gene therapy.

Animals↗
PubMed2001

Efficient oncolysis by a replicating adenovirus (ad) in vivo is critically dependent on tumor expression of primary ad receptors.

Replicating adenoviruses (Ads) are designed to replicate in and destroy cancer cells, generating viral progeny that spread within the tumor. To address the importance of the primary cellular receptor for Ads, the coxsackievirus and Ad receptor (CAR), in permitting intratumoral spread of a replicating Ad, we have used a pair of tumor cell lines differing only in the expression of a primary receptor for Ad5. This novel system thus allowed the first direct evaluation of the relationship between the efficacy of a replicating Ad and the primary receptor levels of the host cell without the confounding influence of other variable cellular factors. We demonstrate that the absence of the primary cellular receptor on the tumor cells restricts the oncolytic potency of a replicating Ad both in vitro and in vivo. Based on these findings, it is apparent that the potential therapeutic advantages afforded by viral replication would be negated by poor intratumoral spread of the viral progeny due to the failure to infect neighboring tumor cells. Because a number of studies have reported that primary cancer cells express only low levels of CAR, our results suggest that strategies to redirect Ads to achieve CAR-independent infection will be necessary to realize the full potential of replicating Ads in the clinical setting.

Adenoviruses, Human↗
PubMed1995

Expression of bone morphogenetic protein-6 messenger RNA in bovine growth plate chondrocytes of different size.

Bone morphogenetic protein-6 (BMP-6) is an osteoinductive factor that may have a regulatory role in the terminal differentiation of chondrocytes. We investigated the expression of BMP-6 messenger RNA in freshly isolated newborn calf rib chondrocytes separated by density gradient centrifugation into five highly enriched subpopulations at different stages of maturation as assessed by cell size and alkaline phosphatase activity. Expression of BMP-6 mRNA was compared with expression of type II collagen mRNA and type X collagen mRNA using Northern analysis. Type X collagen mRNA expression increased with increasing cell size whereas type II collagen mRNA varied little with cell size. BMP-6 mRNA expression was highest in small cells and lowest in the largest cells, which were maximally expressing type X collagen mRNA. This suggests that up-regulation of the BMP-6 gene may precede chondrocyte hypertrophy.

Alkaline Phosphatase↗
PubMed1991

Comparison of collagen propeptides as growth markers in children with inflammatory bowel disease.

The serum concentrations of the carboxy-terminal propeptide of type I procollagen and the amino-terminal propeptide of type III procollagen as biochemical markers of growth activity were compared in 46 children and adolescents with inflammatory bowel disease. Significant correlations were noted between growth velocity and type I procollagen (r = 0.65; P less than 0.001) and type III procollagen concentrations (r = 0.64; P less than 0.001). Although the serum concentration of type I procollagen was generally about 15 times greater than that of type III, the respective serum concentrations were highly correlated (r = 0.66; P less than 0.001) at all growth velocities. The use of daily corticosteroid therapy was associated with significantly lower concentrations of both propeptides (P less than 0.01) than was alternate-day or no corticosteroid therapy, respectively. Children with growth arrest (0.0 cm/mo) had type I and type III procollagen concentrations similar to those found in adults. These observations indicate that the serum concentrations of both collagen propeptides reflect growth activity in children with inflammatory bowel disease and suggest that routine measurement of collagen propeptides may have clinical value in monitoring normal and abnormal growth. The data suggest that the measurement of one propeptide does not offer an advantage over the other.

Adolescent↗
PubMed1991

Effect of calcium/phosphorus ratio on mineral retention in parenterally fed premature infants.

We hypothesized that retention of parenterally delivered calcium (Ca) and phosphorus (P) is affected by the ratio of the delivered minerals and that a 1.7:1 ratio would be optimal since this is the ratio of retention of these minerals by the fetus. Forty-one very low birth weight (VLBW) infants were randomly assigned to one of three total parenteral nutrition (TPN) solutions that were different only in their Ca:P ratios: 2:1 (76 mg/kg/day Ca and 38 mg/kg/day of P), and 1.3:1 (58 mg/kg/day Ca and 45 mg/kg/day P), and 1.3:1 (58 mg/kg/day of Ca and 45 mg/kg/day of P). Serum levels of calcium, phosphorus, and alkaline phosphatase, retentions of calcium and phosphorus and urinary cyclic AMP levels were measured after 48 h on the assigned Ca to P ratio. Calcium retentions were higher with the 2:1 and 1.7:1 ratios and phosphorus retentions were higher with the 1.3:1 and 1.7:1 ratios. The 1.7:1 ratio allowed for the highest absolute retention of both minerals and was the closest to published in utero accretion of calcium and phosphorus. The serum and urine studies demonstrated no abnormalities on any of the three ratios. Cyclic AMPs were not different among groups and were not elevated compared to previous reports suggesting that none resulted in parathyroid hormone (PTH) stimulation. We conclude that the 1.7:1 ratio is better than higher or lower ratios for delivery of calcium and phosphorus in TPN solutions at the quantities studied.

Alkaline Phosphatase↗
PubMed1989

Simultaneous infusion of calcium and phosphorus in parenteral nutrition for premature infants: use of physiologic calcium/phosphorus ratio.

We hypothesized that parenteral delivery of calcium and phosphorus in a ratio of 1.7:1 would promote retention of these minerals and decrease urinary phosphorus excretion, and that delivery of increased amounts of this ratio would result in higher retentions. Serum levels and retention of calcium and phosphorus were measured as calcium intake was increased from 36 to 76 mg/kg/day in 10 mg increments and as phosphorus intake was adjusted to maintain the 1.7:1 ratio. Five different infants were studied at each of the five levels. The amounts of calcium and phosphorus retained increased steadily and at level 5 were 71.8 +/- 1.2 mg/kg/day and 40.9 +/- 1.7 mg/kg/day, respectively. Over the five levels the average percent calcium retention was 91.4 +/- 4.2 and the average percent phosphorus retention was 89.1 +/- 7.7. The provision of parenteral calcium and phosphorus in a 1.7:1 ratio resulted in a balanced retention of both minerals over the range studied. The use of this calcium/phosphorus ratio appears to be appropriate for the preterm infant receiving total parenteral nutrition.

Calcium↗
PubMed1989

Longitudinal assessment of type I procollagen in children with inflammatory bowel disease subjected to surgery.

Using radioimmunoassay we have measured the serum concentrations of the C-terminal propeptide of type I procollagen (pColl-I-C) in 12 Tanner I-II subjects (aged 9-16 years) with severe Crohn's disease (8 patients) or ulcerative colitis (4 patients) and markedly decreased growth velocity who were subjected to surgery and 50 similarly aged children with either ulcerative colitis (20 patients) or Crohn's disease (30 patients) and normal growth. Prior to operation, the mean growth velocity and pColl-I-C concentration in the former group of 12 children were 0.03 +/- 0.02 cm/month (normal greater than or equal to 0.5 cm/month) and 14.1 +/- 1.9 micrograms/dl, respectively. This pColl-I-C concentration is comparable with that previously reported for adults (5-17 micrograms/dl) and significantly lower than found in the 50 normally growing children with inflammatory bowel disease (IBD) (46.9 +/- 2.0 micrograms/dl) (p less than 0.001). All 12 children subjected to surgery had a marked increase in growth velocity and pColl-I-C concentration to 0.73 +/- 0.08 cm/month and 59.1 +/- 5.6 micrograms/dl, respectively (p less than 0.001 compared with preoperative values). Changes in pColl-I-C concentrations antedated measurable changes in linear growth. These data suggest that pColl-I-C concentrations can reflect growth velocity in children with IBD subjected to surgery and may provide a rapidly available measure of current "growth activity."

Adolescent↗
PubMed1989

Effect of high calcium and phosphorus intake on mineral retention in very low birth weight infants chronically treated with furosemide.

The treatment of premature infants with the diuretic furosemide appears to be a contributory factor in the development of metabolic bone disease presumably because of furosemide-induced hypercalciuria. In this study, we measured calcium and phosphorus balance in furosemide-treated very low birth weight infants (VLBW) infants with bronchopulmonary dysplasia (BPD) who were fed a specialized premature formula containing increased amounts of calcium and phosphorus. Furosemide-treated infants received 166 +/- 37 mg/kg/day and retained 80 +/- 34 mg/kg/day of calcium, and 87 +/- 19 mg/kg/day and retained 52 +/- 14 mg/kg/day of phosphorus. The amounts retained were approximately 65% of the calcium and 72% of the phosphorus requirements for in utero mineral accretion. Compared to a group of similarly fed VLBW infants without BPD and not treated with the diuretic, the furosemide-treated infants excreted a larger percent of the calcium intake in the urine but had similar total urinary calcium and phosphorus losses (mg/kg/day) and serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) levels. From the latter two findings, we suggest that the extra mineral content of the formula may have promoted bone mineralization and prevented the occurrence of secondary hyperparathyroidism.

Calcium↗
PubMed1988

Relationship of type I procollagen to corticosteroid therapy in children with inflammatory bowel disease.

We determined the serum concentration of the C-terminal propeptide of type I procollagen (pColl-I-C) in 60 children and adolescents (ages 4 to 17 years) with inflammatory bowel disease (24 ulcerative colitis, 36 Crohn disease) and in seven children (ages 2 to 15 years) with nongastrointestinal disease (asthma) during varying regimens of corticosteroid therapy. Patients with inflammatory bowel disease were grouped according to disease severity (mild, and moderate to severe). Significantly lower pColl-I-C concentrations and growth velocities were found in each severity group among those subjects receiving daily corticosteroid therapy compared with those receiving alternate-day or no corticosteroid therapy (P less than 0.01). When daily corticosteroid therapy was initiated and then maintained for 7 to 14 days in 11 patients with exacerbation of inflammatory bowel disease clinical improvement resulted, but mean procollagen concentrations decreased significantly (P less than 0.001). In seven children with asthma receiving methylprednisolone intravenously, significant decreases in pColl-I-C concentrations were noted within 24 to 48 hours of therapy (P less than 0.001). These data indicate that serum procollagen values decrease during both short- and long-term daily administration of corticosteroid therapy. Longitudinal assessment of procollagen concentrations may provide rapid assessment of the effects of different corticosteroid regimens on growth.

Adolescent↗
PubMed1987

Growth and phosphorus metabolism in premature infants fed human milk, fortified human milk, or special premature formula. Use of serum procollagen as a marker of growth.

Human milk promotes less than optimal growth and is associated with phosphorus deficiency and decreased bone mineralization in very-low-birth-weight (VLBW) infants. In this study, the effects of feeding premature infants either human milk (HM), fortified human milk (FHM), or special premature formula (Similac Special Care [SSC]) on growth, phosphorus metabolism, and serum type I procollagen (pColl-I-C) were evaluated. Infants fed FHM exhibited a rate of weight gain and an increase in head circumference comparable with infants fed SSC and significantly greater than infants fed HM, despite the fact that both the FHM group and the HM group demonstrated biochemical evidence of phosphorus deficiency. The pColl-I-C concentrations in VLBW infants were tenfold to 20-fold greater than concentrations in normal children older than 2 years of age. The pColl-I-C levels correlated positively with weight gain and were significantly greater in the FHM and SSC groups than in the HM group. By contrast, serum alkaline phosphatase levels did not correlate with weight gain and were significantly lower in the rapidly growing SSC group than in either of the two groups with phosphorus deficiency and presumed poor bone mineralization. We conclude that the serum pColl-I-C concentration is a biochemical marker of growth in VLBW infants and may prove useful as a predictor of growth responses to various nutritional and therapeutic interventions.

Blood Proteins↗
PubMed1987

Achievement of in utero retention of calcium and phosphorus accompanied by high calcium excretion in very low birth weight infants fed a fortified formula.

Calcium and phosphorus retention was evaluated in 13 very low birth weight infants who were fed an experimental formula designed to deliver quantities of calcium and phosphorus sufficient to meet the intrauterine accretion rates for these minerals. Retention of calcium and phosphorus in slight excess of these rates was achieved without any apparent difficulties for the infants. Biochemical measurements demonstrated normal serum calcium (9.8 +/- 8 mg/dL) and alkaline phosphatase (242 +/- 51.6 IU) values. However, there was evidence of high tubular reabsorption of phosphate (98.1% +/- 3.3%), hypercalciuria (7.2 +/- 3.8 mg/kg/d), and a relatively low serum phosphorus concentration (5.7 +/- 0.6 mg/dL). This biochemical picture is similar to that seen in phosphorus deficiency except for the low alkaline phosphatase activity. The latter finding, in concert with the high retention of calcium and phosphorus in these balance studies, makes such a diagnosis unlikely. We speculate that this biochemical picture is the result of an inappropriately high calcium/phosphorus ratio.

Alkaline Phosphatase↗
PubMed1987

Phosphorus deficiency syndrome in very low birth weight infants.

Inadequate dietary phosphorus intake is a contributing factor to the occurrence of metabolic bone disease in very low birth weight infants. This article reviews the clinical presentation and the pathophysiology of the phosphorus deficiency syndrome in premature infants. Recommendations for therapy and prevention of phosphorus deficiency are presented.

Bone Diseases, Metabolic↗