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Biomedical subjects

Robert P Heaney

Publications and source records attributed to Robert P Heaney.

At least 19 recordsLinked to original sources
PubMed2003

Low-calcium diet.

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Adaptation, Physiological↗
PubMed2003

Identification of herpes simplex virus RNAs that interact specifically with regulatory protein ICP27 in vivo.

Herpes simplex virus type 1 (HSV-1) protein ICP27 has an essential regulatory role during viral replication, in part by post-transcriptional control of gene expression, and has a counterpart in all herpes viruses sequenced so far. Although much is known about the functions of this signature herpesvirus protein, little is known about its RNA binding capabilities; ICP27 interacts with specificity for a subset of intronless HSV-1 RNAs and poly(G), through its RGG box. We performed an in vivo yeast three-hybrid screen of an HSV-1 genomic library, searching for ICP27 interacting RNAs. Comparable with a yeast genomic screen, 24 of 55 single inserts mapped to antisense strands of HSV-1 transcribed regions or non-transcribed regions. The 31 HSV-1 sense RNAs identified were 35 to 225 nucleotides in length and interacted with preferred specificity for ICP27 as compared with an unrelated RNA-binding protein. They map to 10 monocistronic and 10 polycistronic transcripts of all kinetic classes and represent 28 open reading frames encoding predominantly essential viral proteins with roles in viral DNA replication and virion maturation. Several studies show regulatory effects by ICP27 on the majority of these transcripts, consistent with its regulation of the early-late switch in the HSV-1 life cycle. Deletion of the ICP27 RGG box and the ICP27 M15 mutation, both lethal in virus, abolished or severely reduced the ICP27-RNA interactions, indicating their biological relevance. The study facilitates continued study of gene regulation by ICP27 by further defining its interactions with viral RNAs.

Binding Sites↗
PubMed2003

Calcium and vitamin D.

Calcium and vitamin D are essential for bone maintenance and for treatment-induced bone augmentation. Deficiencies of both nutrients are very common in the age group most afflicted by osteoporosis. Calcium enhancement of estrogen's effects now have been clearly demonstrated. Additionally, all currently approved bone active agents have been tested only in the presence of extra calcium, and newer anabolic agents create a skeletal need for mineral that will require even higher levels of calcium repletion. Prudent nutritional support for osteoporosis prevention and treatment consists of 30 to 40 mmol Ca/d together with sufficient vitamin D to maintain serum 25(OH)D levels above 80 nmol/L (i.e., approximately 25 microg vitamin D/d).

Bone and Bones↗
PubMed2003

Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D.

BACKGROUND: Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency, but the vitamin D status that fully normalizes absorption is not known for humans. OBJECTIVE: To quantify calcium absorption at two levels of vitamin D repletion, using pharmacokinetic methods and commercially marketed calcium supplements. DESIGN: Two experiments performed in the spring of the year, one year apart. In the first, in which participants were pretreated with 25-hydroxyvitamin D (25OHD), mean serum 25OHD concentration was 86.5 nmol/L; and in the other, with no pretreatment, mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a standard low calcium breakfast. A low calcium lunch was provided at mid-day. Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter. METHODS: Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve (AUC) for the load-induced increment in serum total calcium. RESULTS: AUC(9) (+/- SEM), was 3.63 mg hr/dL +/- 0.234 in participants pretreated with 25OHD and 2.20 +/- 0.240 in those not pretreated (P < 0.001). In brief, absorption was 65% higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L (both values within the nominal reference range for this analyte). CONCLUSIONS: Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges, calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus, individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake. We conclude that the lower end of the current reference range is set too low.

Area Under Curve↗
PubMed2003

Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.

BACKGROUND: The cholecalciferol inputs required to achieve or maintain any given serum 25-hydroxycholecalciferol concentration are not known, particularly within ranges comparable to the probable physiologic supply of the vitamin. OBJECTIVES: The objectives were to establish the quantitative relation between steady state cholecalciferol input and the resulting serum 25-hydroxycholecalciferol concentration and to estimate the proportion of the daily requirement during winter that is met by cholecalciferol reserves in body tissue stores. DESIGN: Cholecalciferol was administered daily in controlled oral doses labeled at 0, 25, 125, and 250 micro g cholecalciferol for approximately 20 wk during the winter to 67 men living in Omaha (41.2 degrees N latitude). The time course of serum 25-hydroxycholecalciferol concentration was measured at intervals over the course of treatment. RESULTS: From a mean baseline value of 70.3 nmol/L, equilibrium concentrations of serum 25-hydroxycholecalciferol changed during the winter months in direct proportion to the dose, with a slope of approximately 0.70 nmol/L for each additional 1 micro g cholecalciferol input. The calculated oral input required to sustain the serum 25-hydroxycholecalciferol concentration present before the study (ie, in the autumn) was 12.5 micro g (500 IU)/d, whereas the total amount from all sources (supplement, food, tissue stores) needed to sustain the starting 25-hydroxycholecalciferol concentration was estimated at approximately 96 micro g (approximately 3800 IU)/d. By difference, the tissue stores provided approximately 78-82 micro g/d. CONCLUSIONS: Healthy men seem to use 3000-5000 IU cholecalciferol/d, apparently meeting > 80% of their winter cholecalciferol need with cutaneously synthesized accumulations from solar sources during the preceding summer months. Current recommended vitamin D inputs are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the absence of substantial cutaneous production of vitamin D.

Administration, Oral↗
PubMed2003

Normalizing calcium intake: projected population effects for body weight.

Published data describing the inverse relationship between calcium intake and body weight in 564 women were evaluated for their dispersion around their means, and the fraction above any given weight or rate of weight gain was calculated from the parameters of the normal distribution for the variable concerned. At the 25th percentile of calcium intakes, 15% of young women were overweight, and that fraction fell to only 4% at calcium intakes in the range of currently recommended values. Similarly, obesity prevalence in this cohort fell from 1.4 to 0.2% across the same difference in calcium intakes. At midlife, women at the 25th percentile of intakes gained weight, on average, at a rate of 0.42 kg/y. This gain dropped to -0.011 kg/y at currently recommended calcium intakes. Although calcium intake explains only a small fraction of the variability in weight or weight gain, shifting the mean of the distributions downward by increasing calcium intake can be estimated to reduce the prevalence of overweight and obesity by perhaps as much as 60-80%.

Adult↗
PubMed2003

Quantifying human calcium absorption using pharmacokinetic methods.

Calcium absorption was measured simultaneously by tracer and pharmacokinetic methods in 12 men. The purpose of the study was to calibrate the area under the curve (AUC) for absorptive calcemia to permit comparison or pooling of pharmacokinetic data with tracer-derived estimates. Each subject was studied twice during intake of 500 mg calcium loads (as the carbonate salt), once without excipients, and once with a binder that impeded dissolution of the salt, reducing its absorbability and thereby providing a broad range of absorption values over which to calibrate the method. Various time periods were evaluated, with the best prediction being given by the AUC for the increment in serum calcium calculated over 9 h (AUC(9)). For net absorbed calcium (mmol) the relationship was given by 4.358 x AUC(9) +/- 0.820. The empirical regression coefficient was significant and the error of the estimate (0.820 mmol) acceptably small.

Adult↗
PubMed2003

Is the use of placebo controls ethically permissible in clinical trials of agents intended to reduce fractures in osteoporosis?

Substantial progress has been made in developing treatments that reduce the risk of fractures in osteoporosis. However, available treatments are only partially effective, they are not widely used, and there is need to search for more effective means of fracture prevention. Currently known effective means of reducing fractures were found using randomized placebo-controlled trials. The use of placebo controls in clinical trials has been a subject of significant controversy in recent years. The Declaration of Helsinki revision of October 2000 caused great concern among clinical investigators about the future use of placebo controls if known effective therapeutic agents are available. A working group of ethicists, clinical trial design experts, and clinical investigators examined the current state of knowledge of osteoporosis treatment and trials. They concluded that if placebo controls put subjects at substantial risk of serious outcomes, they are not ethically permissible. Placebo controls in osteoporosis trials with fracture as the measured outcome are permissible only under narrowly defined conditions. Placebo controls may be used if competent, well-informed patients refuse approved therapies for sound reasons, there is a reasonable basis for substantial disagreement or lack of consensus among professionals about whether approved treatments are better than placebos, or subjects are refractory to known effective agents. Active control trials are permissible and desirable if they can be designed and conducted in ways that overcome the interpretive difficulties often associated with such trials.

Clinical Trials as Topic↗
PubMed2003

Got soda?

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Adolescent↗
PubMed2002

Calcium absorption from three salts and CaSO(4)-fortified bread in premenopausal women.

Two studies were conducted to measure calcium absorption from calcium sulfate fortified bread and three salts (calcium lactate, calcium carbonate, and calcium sulfate) in healthy premenopausal women using a crossover design. In study I, calcium fractional absorption levels from the three salts labeled with a stable isotope, 44Ca, were not significantly different (0.039-0.47) as determined by the fecal recovery method. In a second study, absorption of 45Ca from CaSO(4)-fortified labeled bread or labeled milk was measured in serum exactly 5 h postingestion. Fractional calcium absorption was slightly but significantly greater from fortified bread than from milk (mean within subject difference = 0.0675 +/- 0.016). Calcium sulfate is a bioavailable fortificant for white bread that compares favorably with milk and two other salts.

Adsorption↗