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Biomedical subjects

J Rastad

Publications and source records attributed to J Rastad.

At least 163 records · Page 9Linked to original sources
PubMed1987

Quantitative ultrastructural study of boutons of ascending afferents to the feline lateral cervical nucleus.

A quantitative ultrastructural study has been performed of 300 labelled and the same number of unlabelled boutons in the feline lateral cervical nucleus (LCN) of 5 adult cats after cervical or lumbar injections of lectin-conjugated horseradish peroxidase and histochemical reaction with tetramethylbenzidine. On an average the labelled boutons were slightly elongated, had areas of 2.25 micron 2, mitochondrial volume fractions of 11.2% and densities of synaptic vesicles of 35.4.micron-2. The synaptic vesicles were round to flattened with a mean length of 60 nm and length/width ratios of 1.21. The labelled boutons were significantly larger and had significantly lower densities of synaptic vesicles than the unlabelled boutons. The labelled boutons constituted about 14% of the bouton volume of the investigated areas of the LCN. Most of them were axo-dendritic and about 16% synapsed with cell bodies with ultrastructural characteristics similar to the cervico-thalamic projection neurones of the LCN. The number of boutons labelled after the injections comprising 3-5 adjacent segments of the spinal cord was calculated to 6.8 X 10(6). Based on the assumption that they represented terminals of spinocervical tract cells, it was calculated that each of these cells in the lumbar cord gives rise to an average of 4400 boutons in the LCN.

Afferent Pathways↗
PubMed1987

Dimethyl sulfoxide increases cytoplasmic Ca2+ concentration and inhibits parathyroid hormone release in normal bovine and pathological human parathyroid cells.

The acute effects of dimethyl sulfoxide (DMSO) on parathyroid hormone (PTH) release and the cytoplasmic Ca2+ concentration (Ca2+i) were studied in dispersed bovine cells and cells isolated from human parathyroid adenomas. At extracellular Ca2+ concentrations in the 0.5-3.0 mM range, but not at less than 25 nM, addition of 2% DMSO caused a rapid rise of Ca2+i. This effect corresponded to an inhibition of PTH release and there was a strong negative correlation between Ca2+i and secretion. The actions of DMSO on Ca2+i and PTH release were less pronounced in the pathological human cells. The data are consistent with a DMSO effect on the Ca2+-sensor function of the parathyroid cell, possibly mediated by an altered plasma membrane fluidity.

Adenoma↗
PubMed1987

Monoclonal anti-parathyroid antibodies interfering with a Ca2+-sensor of human parathyroid cells.

Previous findings indicate that binding of Ca2+ to an external receptor is part of the mechanism by which extracellular Ca2+ regulates cytoplasmic Ca2+ and hormone release of parathyroid cells. We now present evidence that two newly generated monoclonal anti-parathyroid antibodies react with structures involved in this sensing and/or gating of Ca2+. Microfluorimetric studies of fura 2-loaded human parathyroid cells thus revealed that the antibodies competed with Ca2+ and antagonized the rise in cytoplasmic Ca2+ normally obtained when parathyroid cells are exposed to increasing concentrations of extracellular Ca2+.

Antibodies, Monoclonal↗
PubMed1987

Bimodal regulation of secretion by cytoplasmic Ca2+ as demonstrated by the parathyroid.

Bovine parathyroid cells were used to study parathyroid hormone (PTH) release and the cytoplasmic Ca2+ concentration (Cai2+). When the extracellular Ca2+ concentration was decreased from 3.0 to 0.5 mM, perifused cells reacted with rapid stimulation of PTH release. However, a further reduction of extracellular Ca2+ to less than 10 nM resulted in prompt inhibition. Both effects were readily reversible. Using the intracellular Ca2+ indicator quin-2 also as a buffer for calcium it was possible to control Cai2+ within the 20-600 nM range. PTH release was found to increase with Cai2+ up to 200 nM but was gradually suppressed above this concentration.

Aminoquinolines↗
PubMed1987

Cytoplasmic Ca2+ concentration of single normal human and bovine parathyroid cells measured by dual wavelength microfluorometry.

Dual wavelength microfluorometry was utilized to measure the cytoplasmic calcium concentration (Cai2+) of single parathyroid cells loaded with the indicator fura-2. The method enabled the first registrations of Cai2+ of normal human parathyroid cells, available only in minute numbers. At 0.5 mM extracellular Ca2+, the Cai2+ levels were similar in normal human and bovine cells. Both cell types responded with an initial Cai2+ transient followed by a sustained increase when raising extracellular Ca2+ to 3.0 mM. The sustained effect exhibited a sigmoidal relation to extracellular Ca2+ in the 0.5-3.0 mM range. Although the increase was somewhat greater in the human cells, the half maximal responses were obtained at almost identical extracellular Ca2+ concentrations. Whereas K+ depolarization decreased Cai2+, the Ca2+ channel blocker D-600 had dual actions, raising Cai2+ at 0.5 mM Ca2+ and decreasing it at 3.0 mM Ca2+, and the effects were similar in the bovine and human cells. The present experimental approach verified the validity of utilizing bovine cells as controls in studies of human parathyroid tissue and it appears suitable for analysis of the role of different subpopulations of parathyroid cells in the abnormal parathyroid tissue of patients with hyperparathyroidism.

Animals↗
PubMed1987

Monoclonal antibodies with exclusive reactivity against parathyroid cells and tubule cells of the kidney.

Four monoclonal anti-parathyroid antibodies were generated after immunization of mice with intact cells from human parathyroid tissue. All four monoclonal antibodies reacted in immunohistochemistry with structures present on parathyroid epithelial cells and proximal-tubule cells of the kidney but were unreactive with all other human tissues investigated. Immunofluorescence microscopy on suspended human parathyroid cells showed that the antibodies reacted with structures present on the cell surface. Two of these antibodies efficiently blocked the increase in cytoplasmic calcium concentration of parathyroid cells that is normally associated with increased concentrations of extracellular calcium. The results indicate that these two antibodies interfere with a calcium-sensing mechanism of parathyroid cells--i.e., a potential calcium receptor by which extracellular calcium regulates cytoplasmic calcium and hormone release in these cells.

Animals↗
PubMed1987

Plasma potassium and phosphate concentrations--influence by adrenaline infusion, beta-blockade and physical exercise.

Infusion of adrenaline into healthy male subjects reduced the plasma concentrations of both potassium and phosphate to a similar extent, in a dose-dependent manner, an effect which was prevented by the administration of propranolol. Ergometer bicycling until exhaustion, which caused marked accumulation of lactic acid in the blood and reduction of pH, induced great elevations of both plasma potassium and phosphate with close relationships between the raised plasma concentrations and the reduction in pH, also during beta-blockade. However, longer-term aerobic exercise, without acidosis, also caused some rise of the potassium and phosphate concentrations. During recovery from anaerobic, but not from aerobic, exercise there was a rapid decrease of the plasma potassium levels while the phosphate values normalized gradually together with pH. From measurements of the ion concentrations both in the femoral effluent of one leg, which carried out maximal isokinetic work, and in the opposite antecubital vein it could be calculated that there was for potassium, but not for phosphate, a post-exercise uptake both in the exercised muscle and in the entire organism, indicating the participation of systemic factors.

Adult↗
PubMed1987

Clodronate treatment in patients with malignancy-associated hypercalcemia.

The possibility of reducing symptomatic hypercalcemia and of maintaining total serum calcium concentrations less than 2.8 mmol/l with clodronate (dichloromethylene bisphosphonate) was evaluated in 28 patients with various types of malignant tumors. Four episodes of hypercalcemic crisis with mean serum calcium concentrations of 4.43 mmol/l were controlled within 4-6 days of intravenous clodronate (4 mg/kg BW/day). This was accompanied by a moderate increase in serum creatinine values which, however, returned to pretreatment levels after therapy withdrawal in all but one case. Oral clodronate successfully reduced a mean serum calcium concentration of 3.16 mmol/l in 22 out of 25 patients after 3-12 days (800-3,200 mg/day). After reversal of the hypercalcemias oral clodronate controlled the serum calcium concentration for up to 42 weeks in six out of 15 patients After discontinuation of initial therapy five of seven recurrent hypercalcemias were successfully treated with oral or intravenous clodronate. Hypocalcemia and subjective side-effects were uncommon. It is concluded that clodronate is a valuable clinical tool in the management of patients with malignancy-associated hypercalcemia.

Administration, Oral↗
PubMed1987

Dynamic tests of parathyroid function for diagnosis of primary hyperparathyroidism in malignancy.

Hypercalcaemia can be caused by malignant diseases as well as by primary hyperparathyroidism (HPT). The two disorders may occur together and an accurate discrimination between them is sometimes not possible from basal measurements of calcium and parathyroid hormone (PTH) concentrations. In primary HPT the regulation of PTH secretion is maintained, albeit the set-point is shifted to a hypercalcaemic value. Therefore, when serum calcium is lowered by ethylene diamine tetra-acetic acid (EDTA) infusions or calcitonin injections, patients with primary HPT display enhanced secretion of PTH already within the hypercalcaemic range, whereas parathyroid function remains suppressed in malignancy-associated hypercalcaemia. Tests based on this principle enable a specific identification of HPT. The present report describes eight hypercalcaemic patients with disseminated malignancy where HPT could be diagnosed by the use of such stimulatory tests.

Adenoma↗
PubMed1987

Development of abnormal parathyroid cell function during monolayer culture and its relation to cellular hypertrophy and proliferation.

Primary cultures of adult bovine parathyroid cells grown for up to 8 days were used to study the relationship between regulation of parathyroid hormone (PTH) release, cytoplasmic Ca2+ (Ca2+i) and cell growth. Cell counting indicated that proliferation was inversely proportional to the seeding density. The culture was associated with cell enlargement without apparent relation to the proliferation rate. Moreover, flow cytometric analysis of the DNA distribution excluded that the hypertrophy was due to a high proportion of the cells being in the S and G2 stages of the cell cycle. With progressive time in culture there was a gradual deterioration of the ability of increasing concentrations of extracellular Ca2+ to suppress PTH secretion and raise Ca2+i. This functional dedifferentiation developed to the same extent despite considerable differences in proliferation rates. The data show that parathyroid cells in monolayer culture develop functional and some of the morphological characteristics of parathyroid cells from patients with hyperparathyroidism and that the functional abnormality seems to be related to hypertrophy but not to proliferation of the cells.

Animals↗
PubMed1987

Parathyroid hormone release in vitro in hyperparathyroidism associated with multiple endocrine neoplasia type 1.

Hyperparathyroidism (HPT) in the syndrome of multiple endocrine neoplasia type 1 (MEN-1) exhibits a different picture regarding its propensity for recurrence compared with sporadic primary HPT. In order to shed further light on the MEN-1 syndrome an investigation in vitro was made of parathyroid hormone (PTH) release of dispersed parathyroid cell from 11 patients with parathyroid hyperplasia associated with MEN-1, 10 patients with single parathyroid adenomas, and 10 preparations of normal bovine parathyroid glands. The two patient groups had the same average serum calcium value prior to surgery. Immunoreactive concentrations of PTH were measured after 2-h incubations at extracellular calcium concentrations of 0.5-3.0 mmol/l. Compared with the normal bovine parathyroid cells, the cells of the MEN-1 patients had a reduced calcium sensitivity of the PTH release and secreted smaller amounts of hormone at both low and high extracellular calcium concentrations. A similar abnormality of the PTH release was found for the cells of the hyperplastic and adenomatous parathyroid glands. Although individual parathyroid glands were investigated in only three MEN-1 patients, the results suggested the secretory regulation to be less defective in the small glands of each patient. It is concluded that in patient groups matched for serum calcium, the parathyroid tissue of MEN-1 patients has an abnormality of the PTH release similar to that of parathyroid adenomas.

Adenoma↗
PubMed1987

Optimal discrimination of mild hyperparathyroidism with total serum calcium, ionized calcium and parathyroid hormone measurements.

The serum concentrations of calcium, albumin and parathyroid hormone (PTH) and the plasma levels of ionized calcium were determined in 124 healthy subjects, 89 patients with primary hyperparathyroidism (HPT), 23 of whom had the syndrome of multiple endocrine neoplasia type 1 (MEN-1) and 43 patients who had hypercalcaemia of other causes than HPT (non-HPT), in most cases due to widespread malignancies. The total serum calcium was corrected for the serum albumin concentration (CaM). Healthy females over the age of 50 had higher CaM, than younger females and the women of all ages also had, higher serum PTH levels than males. For all study groups both the intra- and inter-diurnal variations were small for all the studied variables. Discriminant function and optimal discriminatory limits were calculated with the help of computer programs. A consideration of all the individuals in the discriminant analysis, revealed that measurements of CaM alone separated most HPT patients both from the healthy subjects and from the non-HPT patients. However, when only those who had borderline values (defined as CaM between 2.45 and 2.75 mmol/l) were included it turned out that measurements of ionized calcium markedly improved the delineation of mild HPT from the healthy subjects and that, in addition, PTH measurements helped to exclude those with non-HPT hypercalcaemia. The optimal discriminatory levels of serum calcium were calculated as the levels which caused the minimum loss in terms of misclassification when attention was paid to the relative importance of false positive to false negative classifications and to the prevalence of HPT. The optimal discriminatory level for serum calcium for a weighting ratio between false positive to false negative of 1:1, and a prevalence of HPT of 1%, was calculated to be 2.68 mmol/l and for a prevalence of 50% 2.56 mmol/l. In the latter situation a weighting ratio of 10:1 for false positive to false negative gave a level of 2.63 mmol/l while a weighting ratio of 1:10 corresponded to an optimal discriminatory level of 2.47 mmol/l.

Adolescent↗
PubMed1987

Comparative effects of calcitonin and clodronate in hypercalcaemia.

Both calcitonin and clodronate inhibit bone resorption and have therefore been used as therapy for malignancy-associated hypercalcaemia. In order to evaluate their effects a compilation was made of data from 78 patients receiving oral or intravenous clodronate which was compared with a previous review of the effects of calcitonin. Both drugs induced significant reductions of serum calcium but the decrease was greater with clodronate, particularly when given intravenously. Whereas the response to calcitonin generally was of short duration, clodronate was capable of maintaining normal serum calcium values over several weeks with oral administration. Thus, from the clinical point of view clodronate is a very useful adjunct to the available therapy, but the limited experience so far has not fully outlined its position in the management of patients with hypercalcaemia.

Administration, Oral↗
PubMed1986

Dual effects of a new hypocalcemic agent, WR-2721, on cytoplasmic Ca2+ and parathyroid hormone release of dispersed parathyroid cells from patients with hyperparathyroidism.

The effects of the new hypocalcemic agent, WR-2721, on calcium-regulated parathyroid hormone (PTH) release, cytoplasmic Ca2+ (Ca2+i) and membrane potential were measured in dispersed parathyroid cells from patients with hyperparathyrodisim (HPT). The drug had no effects in the absence of extracellular Ca2+ but acted synergistically with Ca2+ in the 0.5-1.5 mM range by depolarizing the cells, increasing Ca2+i and inhibiting PTH release. Although the depolarizing effect of 3.0 mM Ca2+ was unaffected by WR-2721 the drug antagonized the effect of Ca2+ by decreasing Ca2+i and stimulating PTH release. Whereas the inhibitory actions of WR-2721 on PTH release may result from the activation of the mechanism for Ca2+ gating in the parathyroid cell plasma membrane, the stimulatory effect probably reflects increased intracellular Ca2+ sequestration. The drug is considered potentially important for the treatment of HPT.

Amifostine↗
PubMed1986

Calcium-activated calcium permeability in parathyroid cells.

The Ca2+ receptor mechanism of the parathyroid cell was studied using La3+ as a probe. La3+ was found to bind to the cell surface without further penetration. Measurements of 45Ca fluxes and the cytoplasmic Ca2+ concentration (Ca2+i) revealed a stimulatory component in the action of La3+ on Ca2+ permeability resulting in a rise in Ca2+i. These effects mimicked those obtained when raising the extracellular Ca2+ concentration from 0.5 to 3.0 mM, but the actions of La3+ and Ca2+ were not additive. The results suggest the existence of a novel Ca2+ permeability physiologically activated by binding of Ca2+ to an external receptor.

Animals↗