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Biomedical subjects

J E Harrison

Publications and source records attributed to J E Harrison.

At least 145 records · Page 8Linked to original sources

Evaluation of antiulcer activity of delta9-tetrahydrocannabinol in the Shay rat test.

delta9-Tetrahydrocannabinol (THC) inhibited ulcer formation in the pylorus-ligated rat (Shay rat test). However, this antiulcer activity of THC was substantially less than for the anticholinergic substance tridihexethyl chloride both in terms of degree of activity and potency. In addition, the results of the present study suggested different mechanism(s) of action for the antiulcer effects of these substances.

Animals↗

Long-term treatment of Paget's disease of bone with salmon calcitonin.

Twenty-eight patients with symptomatic Paget's disease of bone were treated with synthetic salmon calcitonin for periods of 9 to 42 months (average, 23 months). Serum alkaline phosphatase concentration and urinary hydroxyproline excretion, which had been elevated before treatment, were decreased by calcitonin treatment in all patients, and some decrease was sustained in 23 in association with variable decreases in pain, heat and stiffness of major joints. Improvement was sustained further in approximately half of these patients; the other half had partial return of symptoms. Calcium absorption was increased in 9 of 10 patients studied; the increase did not correlate with plasma concentrations of parathyroid hormone. The mean endogenous fecal calcium excretion was decreased significantly but there was no significant change in mean urinary calcium excretion. Mean accretion rate of calcium to bone, studied in 10 patients, was decreased by 35% after 6 months of treatment and by a further 23% 1 year later. There was no consistent effect of calcitonin treatment on bone mineral mass. No serious adverse effects of treatment such as allergic reactions were observed. Calcitonin appears to be effective initially in most patients with Paget's disease of bone, but with long-term treatment resistance may be acquired.

Alkaline Phosphatase↗

Partial body calcium measurements on patients with renal failure.

The bone calcium status of 39 patients with chronic renal failure on hemodialysis has been measured by in vivo neutron activation analysis (IVNAA) and reported in terms of a calcium bone index (CaBl) which relates the calcium in a patient to that in a normal person of the same height. In 20 of the 39 cases sequential measurements were made over periods of up to 40 mo. The results are compared with data obtained by radiology and by histological examination of bone biopsies. CaBl values varied from below normal to, in one case, above the range of normal. Many of the higher values were associated with demonstrable osteosclerosis. As found in previous work here with IVNAA, significantly low values of CaBl were associated with vertebral deformities; however, some patients with deformity had normal CaBl values, indicating that these had both local mineral loss (resulting in fracture) and osteosclerosis. Taken all together, the data suggest that more than half the patients have osteosclerosis. Sequential data showed no uniform response to treatment.

Adult↗

In vivo determination of nitrogen using Pu-Be sources.

A mehtod of measuring body nitrogen by neutron capture gamma analysis is described. The neutron flux is provided by four collimated 5 Ci Pu-Be sources, placed to give a bilateral irradiation of the subject. The 10-83 MeV thermal neutron capture gamma rays from 14N are detected by two heavily shielded 5 in X 4 in NaI(Tl) detectors. Results indicate a reproducibility +/-3% (1 SD) for a 10 min irradiation of the chest area, while giving a radiation dose equivalent of 50 mREM.

Activation Analysis↗

Endurance training and body compostition of the elderly.

Body composition was studied in subjects from the seventh decade of life (13 M, 25F), observations being made on recruitment and at selected points over a 1-year program of endurance training. As at younger ages, the women initially had more subcultaneous fat than the men, particularly over the limbs. In both sexes, excess weights (9.3 kg. M; 8.1 kg, F) and average skinfold radings (16.2 mm, M; 21.1mm, F) were greater than in younger adults. Edurance training (1 hr of supervised exercise, 150-200 kcal persession, nominal four sessions per week) progressively reduced skinfold readings, by an average of 1.6 mm at 7 weeks, by 2.4 dependent upon the intensity and the frequency of exercise undertaken by the individual. Total body potassium (40K determinations) agreed well with previous studies of older subjects. Body fat estimated form 40K showed a fair correlation with skinfold estimates of body fat (r=0.69, M; 0.93, F), but absolute precentages were higher by 40K(36.6%, M; 48.7%, F) than by subcutaneous fat measurements (20%, M;32% F). Body potassium increased by 4% over the year of training, 70% of this change, occurring between the 14th and the 52nd week of conditioning. Small gains were also recorded in arm circumference, grip strenght (R but not L) and knee extension force. Neutron activation data showed that both sexes had lower initial bone calcium counts than sedentary middle-aged adults. The sample as a whole showed no calcium loss over the year of training, but the group taking the least exercise did show a significant loss (P less than 0.05). Modest endurance training of an elderly population seems not only to correct loss of cardiorespiratory condition, but also to induce favorable changes in body fat and lean mass.

Aged↗

Rat intestinal and renal calcium-binding proteins.

The effect of vitamin D activity on the major renal Ca-binding protein has been compared with that on the intestinal Ca-binding protein. Using a method based on Ca-binding capacity, these proteins were measured in vitamin D deficient rats after vitamin D treatment for varying periods up to 5 days. Since P deficiency has been shown to stimulate synthesis of the active metabolite 1,25-dihydroxycholecalciferol, a similar experiment was done on rats fed a P-deficient diet for periods up to 21 days. The renal Ca-binding protein was unchanged by vitamin D treatment to vitamin D deficient rats and was only slightly increased (50%) by phosphate deficiency. By comparison, the intestinal protein was increased twofold by vitamin D treatment and fivefold by phosphate deficiency. Results indicate that vitamin D activity has no direct effect on the major renal Ca-binding protein.

Animals↗

Studies on the chlorinating activity of myeloperoxidase.

Two methods were utilized to demonstrate the peroxidation of chloride ion to a free species (HOCl or Cl2) by myeloperoxidase. The peroxidase caused the volatilization of radioactivity from soultions containing hydrogen peroxide and [36Cl]NaCl, and catalyzed the formation of HOCl when solutions contianing these components were passed through a Millipore filter to which the peroxidase was adsorbed. In this flow system, 90 mug of canine myeloperoxidase generated 80 muM HOCl in the presence of 200 muM H2O2 at a rate corresponding to a turnover of 100 min-1. Under these conditions, o-tolidine, whose oxidation can be coupled to Cl- peroxidation in free solution, did not accelerate turnover. In contrast to chloroperoxidase and horseradish peroxidase, myeloperoxidase does not utilize chlorite for chlorination reactions. This oxidant inactivates the enzyme. At low pH, chloride ion suppresses the oxidation of myeloperoxidase (to the stable compound II) by both hydrogen peroxide and hypochlorite. Acceptor chlorination is therefore not a rate-controlling reaction in the myeloperoxidase mechanism, and the potential of the functional peroxidase couple is higher than the HOCl/Cl- couple under chlorinating conditions. The product-forming step may be a reverse of compound I formation at the expense of HOCl, rather than the chlorination of Cl- by a chloroperoxidase-like chlorinating intermediate.

Animals↗

Increased bone mineral content in young adults with familial hypophosphatemic vitamin D refractory rickets.

Seven adults with familial hypophosphatemia have been investigated by histologic and radiographic examination of bone, and estimates of bone mineral status by in vivo neutron activation analysis (IVNAA). Histological examination showed severe osteomalacia and osteosclerosis in all cases. Radiography showed skeletal deformities and other sequelae of severe rickets of childhood in five of the seven cases, with, in addition, thickened well-mineralized bones; the other two showed normal radiographs. IVNAA measurements showed that the first five had greater than normal bone calcium and that the other two had normal values. Thus, in all cases there is a greater than normal total bone tissue (osteoid and mineralized bone together). The quantitative body calcium measurements show clearly that osteosclerosis occurs in familial hypophosphatemia, confirming the opinions based on histological and radiological data. Although there has been occasional reference to this sclerosis in the literature, up to the present it has received little attention.

Adolescent↗

Intestinal calcium-binding protein in animals fed normal and rachitogenic diets: I. Rat studies.

Measurements were made of duodenal calcium-binding protein (CaBP) on rats during development of rickets and, subsequently, following vitamin-D2 treatment. Results showed a poor inverse correlation between duodenal CaBP and rickets. In rats fed a phosphate-deficient rachitogenic diet, duodenal CaBP concentration finally fell below detectable limits, but CaBP was still readily measurable 2 weeks after rickets was clearly established. Following a massive dose of vitamin D2 (50 000 I.U.) to rachitic animals, CaBP was formed. However, a small dose of vitamin D2 (500 I.U. daily for 4 days) was insufficient to demonstrate CaBP synthesis than vitamin-D treatment alone. The rachitogenic diet supplemented with phosphate, which caused osteoporosis but not rickets, inhibited CaBP synthesis. The results suggest that nutritional deficiencies from the rachitogenic diet, in addition to vitamin-D deficiency, inhibited CaBP synthesis.

Animals↗

Intestinal calcium-binding protein in animals fed normal and rachitogenic diets: II. Pig studies.

Experiments were carried out in pigs to investigate the relationship between concentration of intestinal calcium-binding protein (CaBP) and the presence of rickets. Pigs made rachitic by a diet deficient in calcium and in vitamin D had concentrations of intestinal CaBP no less than values obtained on control pigs. These experiments, together with earlier work on rats (Can. J. Physiol. Pharmacol. 1975. 53, 137--143), demonstrate a poor inverse correlation between levels of intestinal CaBP and rickets.

Animals↗

Radioimmunoassay studies of intestinal calcium-binding protein in the pig. I. Identification of intestinal calcium-binding protein in blood and response to a low calcium diet.

We have developed a radioimmunoassay for porcine intestinal calcium-binding protein (CaBP) and have used it to detect CaBP in pig plasma. Plasma CaBP is identical to intestinal CaBP on the basis of immunological activity, molecular size, and molecular charge properties. The plasma CaBP concentration was greater in the portal blood than in mixed venous blood, suggesting that blood CaBP originates in the gut. Two of four 15-week-old littermate pigs were placed on a low calcium diet (0.15% calcium, 0.65% phosphorus) and two on a control diet (0.65% calcium, 0.65% phosphorus). After 2 weeks, the entire small intestine was removed and divided into nine 1.8-m segments. CaBP was assayed in both plasma and intestinal mucosa. When the two pigs on a low calcium diet were compared with two control pigs, there was a general increase in immunoreactive CaBP in both plasma and intestinal mucosa. However, there was no increment in immunoreactive CaBP in the first 1.8-m segment of small intestine. Seventy-one percent of the increment in CaBP occurred distal to the first two segments. The largest fractional low calcium diet effect occurred in the ileum. The mean CaBP concentration for the total small intestine increased by a factor of 1.9. The plasma CaBP concentration increased by a factor of 2.6. In these pigs, plasma CaBP was a more reliable indicator of change in CaBP status than was the measurement in the proximal gut segment which contained the duodenum. The assay of CaBP in blood is convenient and may obviate the sampling errors inherent in intestinal biopsy.

Animals↗

Radioimmunoassay studies of intestinal calcium-binding protein in the pig. II. The distribution of intestinal CaBP in pig tissues.

Using a specific radioimmunoassay for porcine intestinal calcium-binding protein (CaBP), we have measured the concentration of CaBP in the various tissues and organs of normal pigs. Intestinal CaBP was present in highest concentration in the upper small intestine, with lower concentrations in the distal small intestine. Intestinal CaBP was also found, in lower concentrations, in kidney, liver, thyroid, pancreas, and blood. In all other tissues, including parathyroid, bone, skeletal muscle, and brain, CaBP immunoreactivity was undetectable or less than in blood. The elution profile of calcium-binding activity and immunoreactivity from gel filtration analysis of kidney and parathyroid extracts suggest that the calcium-binding protein in the parathyroid gland, and the major calcium-binding protein(s) in the kidney, are chemically and immunochemically different from intestinal CaBP.

Animals↗