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Biomedical subjects

J Rastad

Publications and source records attributed to J Rastad.

At least 181 records · Page 10Linked to original sources

Normalizing effect of Ca2+ ionophore on cytoplasmic Ca2+ and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.

The effects of the Ca2+ ionophore A23187 on parathyroid hormone (PTH) secretion and cytoplasmic free Ca2+ concentration (Ca2+i) were measured at different extracellular Ca2+ concentrations using dispersed cells from patients with hyperparathyroidism (HPT). The addition of a low concentration of the Ca2+ ionophore to quin2-loaded cell preparations resulted in the apparent normalization of calcium-regulated Ca2+i. At all extracellular calcium concentrations Ca2+i reached significantly higher values in the presence of the ionophore and the dose-response relationship was shifted to the left. Under similar conditions calcium-regulated PTH release was correspondingly corrected with an increased suppressibility and left-shifted dose-response relationship. The data render strong support for a disturbed regulation of Ca2+i as a major factor in the pathophysiology of HPT.

Aminoquinolines↗

Histologic parathyroid abnormalities in an autopsy series.

The parathyroid glands from 422 subjects without clinical, biochemical, or advanced histologic signs of renal disease were dissected at autopsy. The glands were evaluated histologically in relation to the subjects' age, sex, histologic renal features, other diseases, and medical therapy. Normal parathyroid glands generally had diffuse cellular arrangements, with variable fat cell content. Increased nodularity was observed, especially in enlarged parathyroid glands. Hyperplasia was present in 7 per cent and adenomas in 2.4 per cent. Hyperplastic glands were often nodular and asymmetric, and numbers of oxyphil cells were frequently increased. Some large nodules were histologically indistinguishable from adenomas. Serum calcium levels were elevated in subjects with adenomas or with hyperplastic glands containing large nodules. The findings seem to indicate that nodularity of the parathyroid tissue is a sign of abnormality and that adenomas may arise from such nodular hyperplasia. Hyperplasia and adenomas were more common in elderly subjects and in those with slight or moderate nephrosclerosis. Other diseases or medical therapy were not found to be correlated with parathyroid weight or histologic features.

Adolescent↗

Prolonged low-intensity exercise raises the serum parathyroid hormone levels.

Twelve healthy males performed 5 h exercise on a bicycle ergometer at a constant work load of approximately 50% of their maximum capacity. The serum concentrations of parathyroid hormone (PTH) increased after the first hour and were continuously elevated throughout the exercise period. The rise in PTH was 5-7% above pre-exercise levels, corresponding to 20-30% of the maximal increase obtained by the same assay during prolonged hypocalcaemia. The probable cause for the rise in PTH was that the plasma ionized calcium tended to be lowered during exercise. Since the total serum calcium concentrations were raised (by 3-5%) during exercise the reduction of the free, ionized, fraction was presumably largely due to increased complex-binding although an outward transport from plasma was not excluded. The serum concentrations of magnesium were gradually reduced during exercise while those of phosphate and potassium were raised throughout, probably as a result of leakage from the working muscle.

Adult↗

Alteration in density, morphology and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.

Dispersed parathyroid cells from normal human and bovine glands and from 10 patients with primary (7 adenomas, 3 hyperplasias) and 4 patients with uraemic hyperparathyroidism (HPT) have been investigated with respect to density, morphology and parathyroid hormone (PTH) release. Percoll density gradients enabled an efficient isolation of viable parathyroid cells which generally banded between 1.035-1.090 g/ml. The average density was significantly higher in cells from the normal than the abnormal glands. The pathological glands contained large chief cells, oxyphil and transitional oxyphil cells and, in one case, water-clear cells which were enriched in fractions with densities below 1.055 g/ml. Measurements of cell diameters revealed an increased proportion of enlarged cells in the preparation of abnormal glands. Nuclear diameters were similar in the normal human glands, adenomas and hyperplasias, but the variability was greater among the adenomas. In comparison to normal bovine parathyroid cells, PTH release of cells from the pathological human glands was reduced and abnormally insensitive to extracellular calcium. The oxyphil and water-clear cells secreted similar amounts of PTH as the chief cells of the abnormal glands. The disturbed PTH release in secondary HPT seemed to be confined mainly to cells within nodules of the hyperplastic glands. The results show that the disturbed hormone regulation in HPT is related to morphological changes of the cells and that buoyant density gradients can be used to accumulate the abnormal cells.

Adenoma↗

Stimulation of parathyroid hormone secretion by EDTA infusion--a test for the differential diagnosis of hypercalcaemia.

A constant EDTA infusion of 24 mg/kg/h during 60-120 min was given to 26 patients with primary hyperparathyroidism (HPT), 8 patients with hypercalcaemia of other origin and 10 healthy control subjects. PTH and ionized calcium concentrations were measured at 5-10 min intervals. In all three groups the infusion caused a linear decrease in plasma ionized calcium. In both the HPT patients and the healthy subjects there was a prompt increase in the serum levels of parathyroid hormone (PTH) until a plateau was reached. The PTH response of the HPT patients appeared already within the hypercalcaemic range and the plateau value was attained at higher levels of PTH and ionized calcium than in the healthy subjects. The enhanced response distinguished half of the HPT patients with basal PTH values within the reference range from the healthy controls. The patients with nonhyperparathyroid hypercalcaemia displayed no increase in PTH values until the ionized calcium concentration was reduced far into or below the reference range. Thus the EDTA infusion permitted a complete differentiation between HPT and other causes of hypercalcaemia. In most cases an infusion over 30 min was sufficient for this purpose.

Adult↗

Adrenal gland surgery. Preoperative location of lesions, histologic findings and outcome of surgery.

The accuracy of various techniques for preoperative location of adrenal lesions was studied in 55 consecutive cases, and the perioperative course and outcome of surgery were analyzed. CT correctly located 94% of all adrenal tumours, was less accurate (42%) in hyperplasia and gave no false-positive results. Selective angiography revealed 75% of the tumours, but was likewise diagnostically inadequate in adrenal hyperplasia. Adrenal venous sampling correctly located 80% of tumours and of hyperplasia. In hyperplasia it was the single most successful procedure for detecting the site of adrenal hyperfunction. Phlebography gave misleading information in almost 45% of cases. The perioperative complications included splenic rupture necessitating splenectomy (3 cases), superficial wound infection (2), pneumonia (4) and subphrenic abscess (1). There were no perioperative deaths. The study indicated CT to be the principal procedure for preoperative location of adrenal disorders. In some cases with adrenal hyperfunction, venous sampling should be added. Adrenal surgery can be performed with low morbidity and no mortality and with favourable long-term outlook in cases of benign lesion.

Adolescent↗

Light and electron microscopic study of neurones in the feline lateral cervical nucleus with a descending projection.

Nerve cells in the feline lateral cervical nucleus (LCN) with a descending projection were labelled by injections of horseradish peroxidase, in most cases conjugated to wheat germ agglutinin. After small injections into different spinal cord segments in 16 cats the labelled cells were found mainly in the rostral and ventral portions of the ipsilateral LCN, without a detectable topographic organization. Massive bilateral injections were made into the cervical or lumbar enlargement in 6 cats. Unilateral lesions of the dorsolateral funiculus rostral to the injections generally prevented labelling of LCN cells on the same side. The other side was used to calculate the total number of descending LCN neurones and it was estimated that approximately 500 cells projected down the spinal cord. Comparison with the number of labelled cells after the small injections revealed that the descending LCN neurones projected to an average of at least two spinal segments. Quantitative ultrastructural analyses were made of 17 descending neurones from 7 cats subjected to massive unilateral injections into the cervical or lumbar enlargement. The labelled cells constituted a fairly homogeneous population with respect to the investigated somatic and dendritic features. The morphology and relative frequency of the descending neurones indicate that they may constitute parts of the subpopulation of small LCN cells that have previously been assumed to consist of locally ramifying interneurones.

Animals↗

Paradoxical effects of K+ and D-600 on parathyroid hormone secretion and cytoplasmic Ca2+ in normal bovine and pathological human parathyroid cells.

The effects of K+ and the Ca2+ channel blocker D-600 on parathyroid hormone (PTH) release and cytoplasmic Ca2+ activity (Ca2+i) were measured at different Ca2+ concentrations in dispersed parathyroid cells from normal cattle and from patients with hyperparathyroidism. When the extracellular Ca2+ concentration was raised within the 0.5-3.0 mM range Ca2+i increased and PTH secretion was inhibited. There was also a stimulatory effect of Ca2+ on secretion as indicated by a parallel decrease of Ca2+i and PTH release when extracellular Ca2+ was reduced to less than 25 nM. Addition of 30-50 mM K+ stimulated PTH release and lowered Ca2+i. The effect of K+ was less pronounced in the human cells with a decreased suppressability of PTH release. The Ca2+ channel blocker D-600 had no effect on Ca2+i and PTH release in the absence of extracellular Ca2+. However, at 0.5-1.0 mM Ca2+, D-600 increased Ca2+i and inhibited PTH release, whereas the opposite effects were obtained at 3.0 mM Ca2+. The transition from inhibition to stimulation occurred at a higher Ca2+ concentration in the human cells and the right-shift in the dose-effect relationship for Ca2+-inhibited PTH release tended to be normalized by D-600. It is suggested that K+ stimulates PTH release by increasing the intracellular sequestration of Ca2+ and that the reduced response in the parathyroid human cells is due to the fact that Ca2+i already is lowered. D-600 appears to have both Ca2+ agonistic and antagonistic actions in facilitating and inhibiting Ca2+ influx into the parathyroid cells at low and high concentrations of extracellular Ca2+, respectively. D-600 and related drugs are considered potentially important for the treatment of hyperparathyroidism.

Animals↗

Somatotopic termination of spinal afferents to the feline lateral cervical nucleus.

The labelling pattern of the feline lateral cervical nucleus (LCN) was investigated after pressure injections of lectin-conjugated horseradish peroxidase into cervical, thoracic or lumbar segments of the spinal cord. Sixteen cats received a 5-8 nl injection staining large parts of mainly the ipsilateral grey matter of a single segment. Light microscopic examination of frozen sections reacted with tetramethylbenzidine showed a somatotopic organization in the LCN. Rostral segments of the spinal cord projected mainly to rostroventral and medial parts of the ipsilateral LCN, while more caudally located segments projected to more dorsocaudal and lateral parts of the nucleus. Minor contralateral labelling with a similar somatotopic arrangement was seen in animals given cervical and lumbar injections. No significant labelling was found in the LCN of three control animals, the segmental injections of which were engaged mainly into the ipsilateral dorsal columns and the dorsolateral funiculus. Ultrastructural analysis in two animals which received multiple cervical or lumbar injections showed that about 70% of the peroxidase-positive structures in the LCN were boutons and the rest small myelinated axons. The precise termination pattern of ascending afferents to the LCN is compatible with the somatotopic organization of the other relay centres in the spino-cervico-thalamic pathway.

Afferent Pathways↗

Serum osteocalcin levels in normal subjects and patients with primary hyperparathyroidism.

The serum concentrations of osteocalcin were measured by a radioimmunoassay method in 95 apparently healthy subjects of both sexes with ages from 20 to 80 years and in 16 patients with primary hyperparathyroidism. There were no differences for the values between healthy males and females before the age of fifty, whereas the levels were higher in postmenopausal females. The osteocalcin levels were inversely related to age in premenopausal females but not in elder females or in males. The serum osteocalcin levels were raised in patients with primary hyperparathyroidism but with a large overlap against normal values. In all groups there was a positive correlation with the serum alkaline phosphatases. Variations with age should be considered in the interpretation of measurements in females. Furthermore, the increase in the immediate postmenopausal period might have implications for postmenopausal bone loss.

Adult↗

Regional and systemic effects of short-term intense muscular work on plasma concentration and content of total and ionized calcium.

Isokinetic work with one leg was carried out with maximal force for 2 min by five healthy subjects. The concentrations of plasma total calcium and of ionized calcium in the effluent from the leg increased by a mean of 13.6 +/- 1.8% (SD) and 16.2 +/- 2.0%, respectively. The corresponding rises in the resting arm were 7.7 +/- 4.3% and 8.1 +/- 3.0%. There was a close correlation (r = 0.86; P less than 0.001) between the degree of exercise-induced acidosis and the rise in plasma ionized calcium. However, the calcium values normalized both in the leg and in the arm within 5 min after the exercise and were similar at the two measuring sites despite a lower pH in the leg sample. During work there was a reduction of the plasma volume of 11.2 +/- 6.0% in the regional (femoral) and 12.4 +/- 4.2% in the systemic (antecubital) sample (P less than 0.001 compared to baseline values for both measurements). When adjustments were made for the reduction in plasma volume as well as for acidosis it was evident that, despite the apparent increases in the calcium concentrations, there was a net reduction of the plasma ionized calcium content (the total amount of plasma ionized calcium). This decrease was significantly (P less than 0.05) more pronounced in the exercising leg than in the systemic circulation but the difference could largely be explained by higher calcium-lactate complex formation in the leg.

Adult↗

Stimulus-secretion coupling of parathyroid hormone release: studies of 45Ca and 86Rb fluxes.

Pieces of rat parathyroid glands were used to study fluxes of 45Ca and 86Rb. The uptake of 45Ca increased with the extracellular Ca2+ concentration up to at least 5 mM. A rise of extracellular Ca2+ had dual effects on 45Ca efflux in terms of an initial stimulation and a subsequent inhibition. However, K+ depolarization neither affected the uptake nor the efflux of 45Ca indicating a lack of voltage-dependent Ca2+ channels. The depolarization obtained with exposure to Ca2+ cannot be attributed to a decreased K+ permeability, since the 86Rb concentrating ability diminished and the efflux of the isotope increased when parathyroid pieces were exposed to a raised Ca2+ concentration. A stimulation of 86Rb efflux by the Ca2+ ionophore A-23187 indicated that the parathyroid cells possess a K+ permeability activated by cytoplasmic Ca2+. It is suggested that Ca2+ fluxes through channels sensitive to activation by Ca2+ are important both for the membrane potential and the cytoplasmic Ca2+ activity.

Animals↗

Endogenous peroxidase-like activity in the feline dorsal column nuclei and spinal cord.

Endogenous peroxidase-like activity was investigated with a combined light and electron microscopical technique in 15 cats. The lateral cervical nucleus, the dorsal column nuclei, and segments C6 and L5 of the spinal cord were incubated with diaminobenzidine-tetrahydrochloride (DAB) or tetramethylbenzidine (TMB). After histochemical reaction with DAB a considerable amount of activity was found in nerve cells, astrocytes and pericytes. The neuronal labelling was mainly located in mitochondria of axon terminals and in dendrites whereas the astrocytic and pericytic activity was found in cytoplasmic dense bodies. The quantity of stained structures differed considerably between the animals. In TMB reacted tissue endogenous peroxidase-like activity was only sparsely seen. It was found mainly in frozen sections, in which the neuropil and perivascular structures sometimes contained granules and irregular filaments. The significance of the findings is discussed in relation to observations in tracer studies using horseradish peroxidase.

Animals↗

Defective regulation of the cytosolic Ca2+ activity in parathyroid cells from patients with hyperparathyroidism.

The parathyroid hormone (PTH) release and cytosolic Ca2+ activity were determined in normal bovine parathyroid cells and parathyroid cells obtained from patients with hyperparathyroidism (HPT). There was a sigmoid relation between the cytosolic Ca2+ activity and the extracellular calcium concentration between 0.5 and 6.0 mmol/l. The PTH release was inhibited in parallel with the rise in the cytosolic Ca2+ activity. Both the hormone release and the cytosolic Ca2+ activity were lower in cells from human adenomas and hyperplastic glands, and in comparison with the bovine preparations these cells had higher set points for the cytosolic Ca2+ activity and PTH release. There was a close correlation between the individual set points for the cytosolic Ca2+ activity and PTH release in a material containing both normal and pathological cells. The results indicate that the abnormal PTH release characteristic of HPT is due to a defective regulation of the cytosolic Ca2+ activity.

Adenoma↗

Ultrasonic appearance of adenomatous and hyperplastic parathyroid glands.

An investigation was made of the sonographic and histopathologic characteristics of 27 parathyroid adenomas and 11 primary and secondary hyperplastic parathyroid glands demonstrated by ultrasound before surgical confirmation. All the hyperplastic glands and 21 of the adenomas had a homogeneously sonolucent interior structure and a smooth periphery. The adenomas and hyperplastic glands were sonographically indistinguishable except for 5 large adenomas which had areas of varying echodensity and an irregularly nodulated periphery. The ultrasonically inhomogeneous adenomas were histopathologically more heterogeneous with asymmetric, nodular enlargement. One patient had a cystic adenoma. The results are discussed in relation to the ultrasonic appearance of thyroid noduli and lymph nodes being the main source of errors in parathyroid ultrasonography.

Adenoma↗