Three-year changes in bone mineral mass of postmenopausal osteoporotic patients based on neutron activation analysis of the central third of the skeleton.
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Bone and Bones↗
Biomedical subjects
J E Harrison
Publications and source records attributed to J E Harrison.
A possible role of vitamin D in the genesis of parenteral-nutrition-induced metabolic bone disease.
Patients receiving long term parenteral nutrition may develop metabolic bone disease. In all 11 patients studied, histologic studies of bone showed excessive unmineralized bone tissue despite normal plasma 25-hydroxyvitamin D levels. Three patients also had bone pain and fractures and severe urinary loss of calcium and phosphate. Withdrawal of vitamin D from parenteral nutrition solutions was associated with improved histologic findings of bone in all patients, shown by a decrease in osteoid tissue and an increase in tetracycline uptake. In the three patients with symptoms, bone pain subsided, fractures healed, and urinary loss of calcium and phosphate decreased. Thus, vitamin D may be a factor in the genesis of parenteral nutrition-induced metabolic bone disease.
25-Hydroxyvitamin D 2↗
Compound I of myeloperoxidase.
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Animals↗
Immunofluorescent demonstration of myeloperoxidase of phi bodies and rods in leukaemic leucocytes.
Previous studies employing enzyme histocytochemical methods based on the catalysis of the peroxidation of 3,3'-diaminobenzidine (DAB) demonstrated the presence of hydroperoxidase activity in phi bodies and rods of immature leucocytes of patients with active acute myelogenous leukaemia. It could not be determined from these studies whether the DAB oxidation product was demonstrating a single hydroperoxidase, catalase or myeloperoxidase, or both. In the present study, immunofluorescence techniques for the two hydroperoxidases were applied in an attempt to identify this activity specifically. The results obtained indicate that myeloperoxidase is present in the phi bodies and rods, and that this enzyme may be the major or the only hydroperoxidase present. Its activity could account for the peroxidation of DAB under conditions which are more favourable for the demonstration of catalase.
Catalase↗
Differences between the effects of phosphate deficiency and vitamin D deficiency on bone metabolism.
It has been widely believed that phosphate deficiency causes osteomalacia. Based on this belief, the rickets of familial hypophosphatemia has been attributed to phosphate deficiency associated with the hypophosphatemia. The present studies on rats have, however, demonstrated significant differences between the effects of phosphate deficiency on bone metabolism and the characteristic features of rickets. Weanling rats, maintained on a mildly phosphate deficient diet, had hypercalcemia and hypophosphatemia, and impairment of body growth, bone growth, and bone mineralization. The maximum effect was observed at 5 wk; between 5 and 20 wk the rats improved despite persistent hypophosphatemia. Histologically, at 5 wk the bone showed thick unmineralized osteoid seams covering most bone surfaces, but the epiphyseal cartilage was normal. In addition, the excess osteoid readily incorporated tetracycline indicating normal mineralization and, based on a new sequential pulse labeling technique, the linear bone apposition rate (LBA) was significantly (p < 0.001) increased above control values. This increase was observed within the initial 4 days of phosphate (P) deficiency and persisted up to 15 wk. This effect of P deficiency on LBA was dependent on vitamin D activity. At 4 wk, the mean LBA was 0.106 +/- 0.003 (1 SE) in control rats, 0.149 +/- 0.008 microns/hr in P deficient rats, 0.083 +/- 0.004 microns/hr in vitamin D deficient rats and 0.086 +/- 0.006 microns/hr in rats deficient in both P and vitamin D. We have reported a similar increase in LBA with parathyroid hormone activity. With vitamin D deficiency, phosphate deficient rats showed all the characteristic features of rickets; disorganization of epiphyseal cartilage, excessive unmineralized osteoid, and reduced mineralization based on the incorporation of tetracycline. We conclude that the effects of phosphate deficiency on bone metabolism more closely resembles the effects of PTH activity than the characteristic effects of osteomalacia and rickets.
Animals↗
Effect of thyrotoxicosis and its treatment on bone mineral and muscle mass.
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Adult↗
Metabolic bone disease in patients receiving long-term total parenteral nutrition.
We have prospectively investigated calcium and bone metabolism in 16 patients receiving total parenteral nutrition for periods ranging from 7 to 89 months. In 12 patients, bone biopsies at 6 to 73 months after the start of parenteral nutrition showed osteomalacia. Plasma 25-hydroxyvitamin D levels were normal in all patients. Seven persons developed hypercalcemia, and 10 had hypercalciuria with a negative calcium balance. Serum phosphorus was normal and plasma parathyroid hormone level, normal or decreased. Three patients with the severest form of the disease had vitamin D withdrawn from their solutions. Subsequently, urinary calcium decreased, and serum calcium became normal; two persons reverted to a positive calcium balance. Thus, patients receiving total parenteral nutrition may develop metabolic bone disease characterized by osteomalacia, hypercalcemia, hypercalciuria, and a negative calcium balance. This may be caused by both defective mineralization and increased bone resorption induced by vitamin D, its metabolites, or another unrecognized factor.
Adult↗
Optical detection of a red-shifted Michaelis complex in the reaction of HCN with ferromyeloperoxidase. Evidence for conformational stabilization of high spin iron (II).
The reaction of HCN with ferromyeloperoxidase involves the sequential formation of two monocyanide complexes. The first complex, which forms immediately on mixing, is characterized by a red shift in the Soret band of the ferroperoxidase, and a dissociation constant (measured as a Michaelis constant) of 0.67 mM. The second complex arises from the first via a first order process, whose maximal rate is 0.095 s-1 at 25 degrees C, pH 7.0. This more stable complex is characterized by a blue shift in the Soret and alpha bands and by an overall dissociation constant in the region of 4.5 microM. This gives a free energy difference between the two complexes of around 3.0 kcal mol-1 and a difference in optical absorption of 15 nm (Soret). The measured Arrhenius activation energy for the conversion of the high energy, long wavelength complex to the low energy, short wavelength complex is 16.3 kcal mol-1. A larger blue shift is observed on protein denaturation (34 nm), after which the two-step binding reaction is not observed. This, and the magnitude of the activation energy in the spontaneous complex interconversion process, shows that the latter is a conformational process. In addition, it can be concluded that the unknown structural feature of the heme site which is responsible for the anomalous red shift in the optical spectrum of native ferromyeloperoxidase, is also the link between the ligand state of the iron and the protein conformation.
Animals↗
In vivo neutron activation analysis for bone calcium (INVAA) in malignant hyperthermia susceptible patients.
Some non-rigid Malignant Hyperthermia Susceptible (MHS) patients have a greater than normal incidence of fractures. Radiologically their long bones are slightly thinner than normal. Excessive numbers of caries because of thin dental enamel may also be present. The Malignant Hyperthermic (MH) defects thus appears to involve cells of bone appendages as well as of muscle. We have measured the concentration of calcium in bone by neutron activation analysis and have found it to be reduced in both non-rigid and rigid malignant hyperthermia susceptible patients. The reductions were particularly marked for the non-rigid patients. Bone calcium concentrations were lower in males than in females and in those under 16 and over 60 years of age. This is additional evidence is favour of the hypothesis that malignant hyperthermia is a widespread defect affecting tissues and organs throughout the body.
Adult↗
In vivo measurements of body protein based on the determination of nitrogen by prompt gamma analysis.
Measurement of nitrogen in the human body gives a measure of total protein in the body. Nitrogen (N) may be measured in vivo by a nuclear technique in which the characteristic nitrogen gamma rays emitted after capture of neutrons are detected and counted. The accuracy (as determined by comparison of the measurement of nitrogen in a pig by nuclear and chemical methods) is better than 10%. The reproducibility is less than 6%. The radiation dose is about 5 millirads. This method had been used with 43 patients and 23 normal volunteers and the results are reported. The data are presented in the from of total N content, percentage N by weight, and as a comparison of N and potassium (K) in the body. It is found that the mean percentage of N in the normal males is 2.5%, giving a value of 1.75 kg in the 70-kg standard man. The mean percentage values are not greatly different between normal volunteers and malnourished patients. Taking all subjects, N/K ratios ranged from 7.5 to 20 g/g. Thus K cannot be used as a predictor of N. Nitrogen content of normals correlates well (r = 0.68) with height squared; for malnourished patients there is again a good correlation (r = 0.81) but the regression line for patients is approximately 34% below that for the volunteers consistent with their depleted state.
Animals↗
The amino acid sequence of porcine intestinal calcium-binding protein.
The complete amino acid sequence of the calcium-binding protein (CaBP) from pig intestinal mucosa has been determined: Ac-Ser-Ala-Gln-Lys-Ser-Pro-Ala-Glu-Leu-Lys-Ser-Ile-Phe-Glu-Lys-Tyr-Ala-Ala-Lys-Glu-Gly-Asp-Pro-Asn-Gln-Leu-Ser-Lys-Glu-Glu-Leu-Lys-Gln-Leu-Ile-Gln-Ala-Glu-Phe-Pro-Ser-Leu-Leu-Lys-Gly-Pro-Arg-Thr-Leu-Asp-Asp-Leu-Phe-Gln-Glu-Leu-Asp-Lys-Asn-Gly-Asn-Gly-Glu-Val-Ser-Phe-Glu-Glu-Phe-Gln-Val-Leu-Val-Lys-Lys-Ile-Ser-Gln-OH. The N-terminal octapeptide sequence was determined by mass spectrometric analysis by Morris and Dell. The first 45 residues of bovine CaBP differ only in six positions from the corresponding sequence of the porcine protein, except that the sequence starts in position two of the porcine sequence. The mammalian intestinal CaBP's belong to the troponin-C superfamily on the basis of an analysis by Barker and Dayhoff.
Amino Acid Sequence↗
Phophate-induced renal calcification in the rat.
Studies were done to investigate nephrocalcinosis produced in weanling female Wistar rats fed pelleted, semisynthetic diets. The rats were fed diets varying in concentrations of Ca and P supplied as inorganic salts for periods of 4--6 weeks and results compared with control rats fed laboratory rodent chow for the same period of time. Measurement of renal Ca and P concentrations showed that nephrocalcinosis was produced by semisynthetic diets with inorganic phosphate concentrations as low as 0.5% on a weight basis; in contrast, rats fed regular laboratory chow (P = 0.72%) showed no evidence of nephrocalcinosis. The severity of the lesion was proportional to dietary phosphate concentrations from 0.5 to 1.0% but other dietary factors modified the severity of the lesion. With the lower dietary phosphate of 0.5%, increasing dietary Ca from 0.5 to 1.0% decreased the severity of the renal calcification. Decreasing protein concentrations from 25 to 15% casein increased the severity of the renal lesions. Other dietary factors also appear to modify the phosphate-induced nephrocalcinosis since no lesions occurred in rats on laboratory chow. It is suggested that the availability of dietary phosphate may be a factor. The phosphate in the semisynthetic diets was totally inorganic while the natural foods of laboratory chow contain, at least in part, organic phosphate.
Animals↗
Myeloperoxidase: confirmation and nature of heme-binding inequivalence. Resolution of a carbonyl-substituted heme.
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Binding Sites↗
Myeloperoxidase and singlet oxygen: a reappraisal.
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Benzofurans↗
Cytochrome P450 cam: SS- dimer and -SH derivative reactivities.
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Alkylation↗
Calcium metabolism in adult outpatients with epilepsy receiving long-term anticonvulsant therapy.
Long-term anticonvulsant drug therapy may lead to abnormalities of calcium metabolism resulting in osteomalacia. The prevalence and severity of altered calcium metabolism was studied in an adult outpatient population of persons with epilepsy receiving anticonvulsant therapy for a minimum of 2 years. Assessment of calcium metabolism was based on serum concentrations of calcium, phosphorus, alkaline phosphatase and 25-hydroxycholecalciferol and of plasma parathyroid hormone, intestinal absorption of isotopic calcium and skeletal bone mineral mass as determined by in vivo neutron activation or x-ray photodensitometry.Thirty-nine patients who had been receiving anticonvulsant therapy for an average of 20 years were studied; none had clinical evidence of metabolic bone disease. Decreased serum calcium concentration was noted in 10%, decreased serum phosphorus concentration in 10% and elevated serum alkaline phosphatase concentration in 44%. The mean serum 25-hydroxycholecalciferol concentration was significantly lower (P < 0.001) than in a control group (11.6 v. 19.6 mg/mL). None of 18 patients studied had an increased plasma concentration of parathyroid hormone, and only 1 of 17 patients had decreased intestinal absorption of isotopic calcium. Bone mineral mass was decreased in 44% of 32 patients studied.It was concluded that long-term treatment with anticonvulsant drugs leads to mild abnormalities of calcium metabolism and decreased bone mineral mass in a substantial percentage of adult outpatients with epilepsy. These abnormalities probably predispose the patients to the development of clinically significant metabolic bone disease.
Adult↗
A self-powered, preprogrammable, constant current, electronic stimulator for implantation in conscious and unrestrained, small animals.
A completely implantable electronic brain stimulator was designed and constructed using commercially available Complementary Metal Oxide Semiconductor digital, integrated circuits. All stimulation parameters were preprogrammed prior to implantation. They included bipolar pulse width (0.5 msec), constant current intensity (120 muA) and frequency (125 pulses/sec) as well as pulse train length (33 sec) and the interval between pulse trains (70 min). After complete encapsulation, the unit weighed 6.2 g and measured 30 mm X 15 mm X 8 mm. The units were easily implanted under the skin in the flank areas of 300 g rats. The 5 muW power consumption allowed implanted lifetimes of over 6 months. A miniature magnetic switch was included inside the package to allow testing of the unit after implantation. Stimulators were implanted in 17 rats for periods of 4--62 days in a study exploring the relationship between long term electrical stimulation of the lateral hypothalamus and the development of arterial pathology.
Animals↗
Bone apposition rate as an index of bone metabolism.
The rate of bone apposition was studied by labeling bone with four or five sequential doses of oxytetracycline given at equal intervals of 2 or 4 days in rats and rabbits. The rate was estimated in bone formation sites bearing all the doses. This method has the advantage of assessing the rate of new bone mineralization during the active bone-forming phase only. This index of bone formation was found to be independent of the location of bone samples in the skeleton, and therefore might be under the influence of general body mechanisms only. Preliminary study in the rats indeed yielded results indicating that this bone apposition rate is accelerated by dietary deficiency in calcium.
Animals↗