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Biomedical subjects

J Rastad

Publications and source records attributed to J Rastad.

At least 145 records · Page 8Linked to original sources
PubMed1988

Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism.

When raising the extracellular Ca2+ concentration stepwise from 0.5 to 3.0 mM, bovine parathyroid cells reacted with initial transient and sustained elevations of the cytoplasmic Ca2+ concentration (Ca2+i), as well as more than 50% inhibition of parathyroid hormone (PTH) release. Human parathyroid adenoma cells and bovine cells cultured for 1 day or exposed to a low concentration of a monoclonal antiparathyroid antibody exhibited right-shifted dependencies of PTH release and Ca2+i on extracellular Ca2+ and reduced Ca2+i transients. The protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) further right-shifted the dose response relationship for Ca2+ regulated Ca2+i of the adenoma cells, whereas the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) tended to normalize it, without affecting Ca2+i of normal bovine cells. In cells from an oxyphil adenoma and a parathyroid carcinoma as well as in bovine cells cultured 4 days or exposed to a high concentration of the antiparathyroid antibody, there were no Ca2+i transients, very small increases in steady-state Ca2+i and nonsuppressible PTH release. The results suggest that reduced availability of a putative Ca2+-receptor and increased protein kinase C activity may be important factors in the decreased Ca2+ sensitivity of abnormal parathyroid cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Psychiatric symptoms and cerebrospinal fluid monoamine metabolites in primary hyperparathyroidism.

This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 +/- 9.0 (SD) versus 4.4 +/- 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 +/- 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.

Aged↗
PubMed1988

Maximal isokinetic muscle strength in patients with primary hyperparathyroidism before and after parathyroid surgery.

Primary hyperparathyroidism (HPT) is associated with symptoms of generalized fatigue and muscle weakness. The purpose of this study was to investigate muscular function in HPT quantitatively and to evaluate the effect of parathyroid surgery in this respect. The maximal isokinetic muscle strength (peak torque) of knee extension and flexion was measured with a Cybex-II dynamometer in 16 patients with primary HPT (mean serum calcium 2.81 +/- 0.14 mmol/l), four of whom had subjective impairment of strength, and in nine control patients submitted to hemithyroidectomy due to atoxic thyroid adenoma. Before surgery there was no significant difference in muscle strength between the two groups, neither was there any consistent relationship between the subjective feeling of muscular weakness and the measured peak torque. Seven months after surgery the HPT patients had increased their muscle strength by 8 per cent (P less than 0.05). The improvement was correlated with the pre-operative serum calcium levels (r = 0.56, P = 0.02) and was particularly seen in patients with pre-operative subjective muscular weakness. Patients with only slightly raised calcium values and without subjective muscular symptoms did not benefit clearly from surgery, compared with the controls. The study demonstrates that HPT patients, especially those with neuromuscular symptoms, can improve their muscle strength after parathyroid surgery.

Adult↗
PubMed1988

1,25(OH)2D3 inhibits hormone secretion and proliferation but not functional dedifferentiation of cultured bovine parathyroid cells.

Increasing the extracellular Ca2+ concentration from 0.5 to 3.0 mM induced marked increments in cytoplasmic Ca2+ concentration (Ca2+i) and inhibition of parathyroid hormone (PTH) release of freshly isolated bovine parathyroid cells. 1,25-dihydroxycholecalciferol (1,24(OH)2D3; 0.1-100 ng/ml) did not affect (Ca2+i) and was also without acute effect on the secretion. During 4 days of monolayer culture, the parathyroid cells underwent significant increases in both number and size, and presence of 10-100 ng/ml 1,25(OH)2D3 almost completely inhibited the cell proliferation, whereas the hypertrophy was unaffected. One day of culture with 0.1-100 ng/ml 1,25(OH)2D3 was without effect on PTH release but after 4 days there was a dose-related reduction of secretion. At this time point and irrespective of the culture condition, PTH release was no longer suppressed by high extracellular Ca2+. Furthermore, Ca2+i increased little upon increments in the extracellular Ca2+ concentration as compared with freshly isolated cells. It is concluded that after prolonged exposure to 1,25(OH)2D3, PTH release is inhibited and, at high concentrations, the parathyroid cells cease to proliferate. However, 1,25(OH)2D3 does not affect the development of functional dedifferentiation of parathyroid cells during monolayer culture.

Animals↗
PubMed1988

Calcium-agonistic action of Mn2+ in the parathyroid cell.

The effects of 3.0 mM Mn2+ on parathyroid hormone (PTH) release, 45Ca fluxes and the cytoplasmic Ca2+ concentration (Ca2+i) were studied in vitro with use of parathyroid glands from rats and cattle. Mn2+ inhibited PTH release by about 70 and 60% at Ca2+ concentrations of less than 10 nM or 0.5 mM, respectively, and like the inhibitory effect of Ca2+, that of Mn2+ was rapid and reversible. Mn2+-induced inhibition of the PTH release was associated with reduction of 45Ca uptake by about 50% and a marked but temporary increase in 45Ca efflux. Mn2+ induced a rapid transient increase in Ca2+i provided that the intracellular release of Ca2+ had not already been triggered by previous exposure to 3.0 mM Ca2+. This initial action was apparently followed by influx of Mn2+, since pronounced quenching of the fluorescence from the Ca2+ indicator fura-2 was observed. The results indicate that Mn2+ behaves in several respects like a calcium analogue in parathyroid cells and may inhibit PTH release by interfering directly with the secretory machinery.

Animals↗
PubMed1988

Effects of propranolol and verapamil on plasma ionized calcium and parathyroid hormone in short-term intense isokinetic leg exercise.

Physical exercise, beta-adrenergic stimulation and calcium channel blockade can affect calcium homeostasis. The present study investigated, in eight healthy males, the effects of orally administered propranolol or verapamil during a 2-min maximal, isokinetic, leg exercise. Immediately after exercise the plasma ionized calcium concentrations were increased, in control and drug tests, by 5-6%, and within 5 min of recovery they were almost returned to baseline. Serum parathyroid hormone (PTH) concentrations were unchanged at termination of exercise, but they increased during the first 5 min of recovery, coincident with the decline in calcium concentrations, which, however, were still elevated. Neither verapamil nor propranolol selectively changed basal or exercise plasma ionized calcium or serum PTH concentrations. Muscle strength, blood pH, lactate concentrations and plasma volume changes were not affected by any drug. Verapamil did not have any specific effect on the concentrations of plasma magnesium, phosphate, potassium or sodium while propranolol increased the concentrations of plasma potassium and decreased those of phosphate during exercise as well as recovery.

Adult↗
PubMed1988

Hyperparathyroidism is associated with reduced expression of a parathyroid calcium receptor mechanism defined by monoclonal antiparathyroid antibodies.

Parathyroid tissue from patients with hyperparathyroidism (HPT) exhibited reduced immunohistochemical reactivity with monoclonal antiparathyroid antibodies, previously shown to stain intensely the surface of normal human parathyroid cells and to interfere with a receptor mechanism of these cells which is involved in the sensing and gating of Ca2+. Parathyroid hormone (PTH) release and cytoplasmic Ca2+ concentrations (Ca2+i) of dispersed cells from the pathological parathyroid glands had right-shifted dependencies on extracellular Ca2+, and exposure to the antibodies rendered both Ca2+i and PTH release almost completely insensitive to changes in ambient Ca2+. The results suggest that reduced expression of a parathyroid calcium receptor mechanism may be an important cause for the aberrant PTH release in HPT.

Adenoma↗
PubMed1988

Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism.

Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0.5-3.0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT.

Calcium↗
PubMed1988

Inhibition of cell growth retains differentiated function of bovine parathyroid cells in monolayer culture.

Monolayer culture of bovine parathyroid cells for up to 4 days in medium containing 10% serum resulted in cell hypertrophy and proliferation as well as functional dedifferentiation. Compared to freshly isolated cells there was a right-shifted dose-effect relationship for calcium-inhibited parathyroid hormone (PTH) release, a decreased suppressibility of secretion and an inability of the cytoplasmic Ca2+ concentration (Ca2+i) to follow changes in the extracellular Ca2+ concentration. The functional changes seemed not to be due to culture per se, since human parathyroid cells exhibited an essentially unchanged regulation of Ca2+i even after 8 days of culture in 10% serum. During culture in medium containing 0.1% serum, the bovine cells did not proliferate and there was only slight cell hypertrophy. These cells retained much of their ability to regulate Ca2+i and PTH release. The results indicate that functional dedifferentiation of parathyroid cells is related to cell growth.

Animals↗
PubMed1988

Recurrent hyperparathyroidism due to peroperative seeding of neoplastic or hyperplastic parathyroid tissue. Case report.

The clinical course and histologic characteristics of recurrent hyperparathyroidism due possibly to peroperative seeding of parathyroid cells are described in four cases--two of parathyroid adenoma, one of parathyroid hyperplasia associated with multiple endocrine neoplasia type 1 and one of parathyroid carcinoma. The observations underline the necessity for careful handling of parathyroid lesions during extirpation, and that the multiple nodules of implanted parathyroid tissue can be curatively excised in some cases.

Adult↗
PubMed1988

Dimethyl sulfoxide inhibits proliferation but not hypertrophy and functional dedifferentiation of bovine parathyroid cells in culture.

Primary cultures of bovine parathyroid cells were used to study the relationship between parathyroid hormone (PTH) release, regulation of the cytoplasmic Ca2+ concentration (Ca2+i) and cell growth. Parathyroid cells were seeded into fibronectin-coated culture wells in the absence (control) or presence of 2% (v/v) dimethyl sulfoxide (DMSO). Both groups of cells attached and flattened out, and during 4 days of culture the cell diameters and protein content increased. However, whereas the number of cells in the control group increased by 60% and their 3H-thymidine incorporation tenfold, the DMSO cultured cells exhibited no signs of cell proliferation. Despite this difference in cell replication rate both groups of cells developed similar functional dedifferentiation. There was consequently a decreased Ca2+ suppressibility of PTH release, and Ca2+i did not follow the ambient Ca2+ concentration in a usual manner. It is concluded that during culture bovine parathyroid cells develop morphological and functional abnormalities similar those in parathyroid cells from patients with hyperparathyroidism. Moreover, this functional dedifferentiation could be dissociated from increased cell proliferation but may be related to cell hypertrophy.

Animals↗
PubMed1988

Cytosolic free calcium in platelets: relationships to blood pressure and indices of systemic calcium metabolism.

Relationships between cytosolic free calcium ([Ca2+]i) in platelets, indices of systemic calcium metabolism and blood pressure were examined in 86 subjects; 29 patients with untreated and 29 patients with treated essential hypertension, six patients with borderline hypertension and 22 healthy reference subjects. In order to analyse interactions between the variables, multivariate statistical analyses were employed. The patients with untreated hypertension had higher [Ca2+]i values in non-activated platelets (P = 0.04) and lower levels of plasma ionized calcium (P = 0.02) than the reference subjects. In multivariate models analysing platelet [Ca2+]i mean blood pressure (MBP), plasma ionized calcium, serum parathyroid hormone (PTH) and body mass index (BMI), the relationship between platelet [Ca2+]i and blood pressure was attenuated (P = 0.13), whereas the inverse relationships between plasma ionized calcium and MBP (P = 0.01) and between platelet [Ca2+]i and serum PTH (P = 0.06) seen in univariate analyses persisted. According to the multivariate models the [Ca2+]i value explained only 5% of the MBP variability. Thus, the data from this investigation do not support a close relationship between basal platelet [Ca2+]i and blood pressure. The inverse relationship between plasma ionized calcium and blood pressure, independent of platelet [Ca2+]i and serum PTH, suggests a direct interaction between plasma ionized calcium and blood pressure regulation.

Adolescent↗