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Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 199 records · Page 11Linked to original sources
PubMed1983

Effects of two treatment regimes with synthetic human parathyroid hormone fragment on bone formation and the tissue balance of trabecular bone in greyhounds.

The adult greyhound was found to be similar to adult man with respect to kinetic and histomorphometric indices of calcium metabolism. The relationship between trabecular bone tissue balance and the pattern of human PTH fragment 1-34 (hPTH 1-34) administration by daily injections or continuous sc infusions was investigated in this model and the results compared to those from a clinical trial of hPTH 1-34 in involutional osteoporosis (peptide administration by single daily injections). In the dogs, the daily injection regime elevated plasma levels of immunoreactive hPTH 1-34 for no more than 4 h/day. The greyhounds so treated showed significantly increased indices of bone formation (surface osteoid, plasma alkaline phosphatase activity, and skeletal accretion rate of calcium) and resorption (number of osteoclasts, resorption surfaces). Iliac trabecular bone volume increased significantly, as it did in the patients. The infusions did not significantly increase the trabecular bone volume or the 47Ca accretion rate, two parameters which increased in parallel in dogs and patients treated successfully by daily injections. The osteoclastic surfaces, however, were clearly increased by continuous infusions, while the increases in the osteoblastic surfaces were less statistically significant. Since hPTH 1-34 may inhibit osteogenesis in Friedenstein chambers, it is possible that the increased osteoblastic activity induced by the daily injection regime in trabecular bone is dependent on the noncontinuous nature of the PTH stimulus.

Animals↗
PubMed1983

Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs.

Nine dogs were infused at constant rates with the synthetic parathyroid peptide hPTH 1-34 (initially sc) to produce consistent hypercalcaemia. Over the final week, the infusions were iv. Radioisotopic tracers were injected iv 30 days (5 dogs) and 2 days (9 dogs) before the infusions were suddenly terminated. In 5 dogs, complete urine collections were obtained via a bladder catheter over 8 h beginning 2 h before stopping the infusions. Cessation of treatment caused small rises in the urinary Ca: creatinine ratio. Plasma calcium levels fell by a mean of 0.44 mmol/l, of which total urine calcium excretion only accounted for 55%. Immediately after the PTH infusions were stopped, consistent but transient increases were seen in the ratio of 'new' 47Ca to 'old' 45Ca label, suggesting inflow of 40Ca of high 47Ca specific activity from a fairly rapidly exchangeable bone pool. These data confirm and extend previous evidence that the immediate response of the calcium equilibrium between bone and bloodstream to rapid changes in plasma PTH concentrations in the supra-physiological range is paradoxical relative to the classical later response.

Animals↗
PubMed1982

Rapid high-yield purification of neuropeptides from canine intestinal muscle.

A simplified method for purification of gastrointestinal neuropeptides from relatively small amounts of tissue is described. Sequential adsorption, gel filtration, ion-exchange chromatography, and high-performance liquid chromatography without lyophilization produced good yields of somatostatin, bombesin, and vasoactive intestinal polypeptide immunoreactivity. The method is suitable for simultaneous purification of several small, basic peptides from limited amounts of starting material.

Animals↗
PubMed1982

Regional bone density measurements compared to total body calcium in osteoporosis.

In 21 women with crush fracture osteoporosis quantities related to trabecular bone density in lumbar vertebrae and in the distal radius were significantly correlated (r = 0.50, P less than 0.05). When the group was enlarged to include data from other patients without osteoporosis, a higher coefficient of correlation was obtained (r = 0.69, P less than 0.001). Total body calcium, measured by in vivo neutron activation analysis, was significantly correlated to quantities related to cortical bone mass in the radius and femur. Thus, these quantities could be used to make estimates of total body calcium in osteoporotic patients. There was no significant correlation between total body calcium and quantities related to trabecular bone density, measured by computed tomography, in vertebrae or in the distal radius.

Bone and Bones↗
PubMed1982

Rates of new bone formation in patients with crush fracture osteoporosis.

1. Calcium balances and formation rates of new bone measured with an improved tracer technique using 85Sr have been determined simultaneously in 21 patients with idiopathic osteoporosis and vertebral crush fractures. 2. A weak positive association was found between calcium balance and the kinetically measured calcium accretion rate, which is the sum of the true rate of bone formation and various long-term exchange processes. 3. The more negative balances were associated with significantly greater early loss of tracer taken up into bone by 'accretion', so that long-term (greater than 200 day) uptake was reduced. 4. This indicates that patients actively losing bone mineral have lower true rates of bone formation and higher rates of long-term exchange than their fellow patients who are more nearly in calcium equilibrium. 5. No statistically significant association was found between measured rates of bone resorption and calcium balance.

Aged↗
PubMed1982

Interpretation of tracer studies on plasma protein turnover: comparison of methods and optimization of techniques.

1. A comparison of several published methods for analysing plasma protein turnover data has been undertaken, with particular reference to rapidly metabolized proteins such as members of the complement series. 2. With the exception of the equilibrium time method, most methods proved adequate for the determination of overall fractional catabolic rates. A further exception is that the renal clearance method becomes invalid when the fractional catabolic rate approaches the renal iodide clearance, but this may be the method of choice for slowly metabolized proteins if accurate urine collections can be ensured. 3. For the measurement of the ratio of extra to intra-vascular protein pool size a clear preference emerged for the method of C. M. E. Matthews (1957, Physics in Medicine and Biology, 2, 36-53). For rapidly metabolized proteins the calculations must be preceded by a correction for the non-protein bound iodide retained in the intra- and extra-vascular spaces. 4. The accurate calculation of fractional catabolic rate in the extravascular pool generally requires more experimental data than are commonly collected as well as an accurate correction for non-protein bound label that remains unexcreted. Only two techniques hold promise of accurate results: Nosslin's rate equations method and a development of Vitek's deconvolution method described herein. Nosslin's integrated rate equations method is particularly affected by systematic errors in renal iodide clearance estimates and should probably not be further used for this purpose.

Blood Chemical Analysis↗
PubMed1982

Bone rarefaction and crush fractures in juvenile chronic arthritis.

Seventy children with juvenile chronic arthritis have had measurements of cortical and trabecular bone density in one or both radii. In 7 children with unilateral disease of one wrist, there was a substantial reduction in growth on the affected side. Trabecular bone density in the distal radius was reduced in the main group of 63 patients compared with controls, and this deficit was appreciably worse if the wrist was clinically affected by disease or if the child was being treated with steroids. Cortical bone density in the midshaft was less affected. Crush fractures of the spine were associated with more prolonged periods of bed rest, steroid therapy, radial trabecular bone density more than 2 standard deviations below normal, and subnormal 25-hydroxycholecalciferol concentrations in the serum. Since steroid therapy is often mandatory the main therapeutic implications are that the more severely affected child often needs vitamin D supplementation in "physiological" dosage, and that early mobilisation and reduction of steroid dosage should be constant aims.

25-Hydroxyvitamin D 2↗
PubMed1982

Long-term treatment of osteoporosis with 24,25 dihydroxycholecalciferol.

Five patients with involutional osteoporosis were treated with 24,25 dihydroxycholecalciferol (24,25-(OH)2D3) for 6 months, in doses sufficient to double plasma levels at that time. Dietary calcium absorption transiently improved by nearly 2 mmol Ca per day at 2 weeks, but this effect was lost by 6 months. The calcium and phosphate balances followed the trends in calcium absorption. Only twenty-five dihydroxyvitamin D levels changed little. Histomorphometric and kinetic indices of new bone formation and bone blood flow remained stable but there was an increase in urine hydroxyproline at 6 months, which was of borderline statistical significance. Treatment at this dosage of 24,25(OH)2D3, which increased plasma levels within the physiological range, conferred no measurable long-term benefit on our patients. Larger doses, or combination therapy, may warrant further clinical evaluation in osteoporosis.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

Steady state relations between control proteins regulating the formation of the alternative pathway C3 convertase.

A steady state algebraic Mass Action analysis of the factors controlling the concentration of the alternative pathway C3 convertase is presented. The positive feedback loop does not make this portion of the complement system insensitive to variation in control protein concentrations; on the contrary, a hyperbolic relationship is revealed between C3 convertase and a complex product of the control protein concentrations which contains some mathematical non-linearities. The consequences of this relationship are explored. It is found that variations in the concentration of any one control protein will have an effect which can only be predicted if its initial concentration and those of the other control proteins are known. The system is capable of responding with a considerable range of amplitudes to a given signal which raises the question as to whether the feedback loop confers biological advantage, not only by augmenting the activation of C3 to C3b, but through its potential for flexibility in responding to an activating stimulus. The analysis may also prove useful in the design and evaluation of experiments to determine the reaction rate constants governing the interactions between the control proteins in the fluid phase in vitro.

Complement Activating Enzymes↗
PubMed1981

Skeletal blood flow in Paget's disease of bone.

Using a modified plasma clearance technique, with 18F as a tracer, it is possible to measure blood flow to bone in man. In the normal adult skeleton, blood flow amounts to about 300 ml/min. In untreated Paget's disease of bone there is a striking increase, which is proportional to the biochemical severity of the disease : total blood flow to the skeleton is approximately doubled at an alkaline phosphatase of 50 KAu/dl (i.e. about four times the normal upper limit). Treatment with calcitonin brings a rapid return to normal, possibly before there is a detectable biochemical response. This may explain the rapid pain relief often reported on starting treatment with calcitonin.

Adult↗
PubMed1981

Cloning of bacteriophage T5 DNA fragments. III. Expression in Escherichia coli mini-cells.

Use has been made of the mini-cell system to study polypeptide synthesis from cloned EcoRI, HindIII and PstI fragments of T5 DNA. The correlation of certain gene products with known genes has been established, as well as the physical mapping of genes not yet identified genetically. In some cases, it has been possible to demonstrate the presence of T5 promoters on the cloned DNA fragments. The design of experiments to avoid certain artifacts inherent in the use of the mini-cell system is discussed.

Bacteriophage lambda↗
PubMed1980

Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.

Aged↗