The Experts below are selected from a list of 1560 Experts worldwide ranked by ideXlab platform
Göran Åkerström - One of the best experts on this subject based on the ideXlab platform.
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alteration in density morphology and Parathyroid Hormone Release of dispersed Parathyroid cells from patients with hyperParathyroidism
Apmis, 2009Co-Authors: Claes Rudberg, Jonas Rastad, Sverker Ljunghall, Leif Wide, Lars Grimelius, Henry Johansson, Rolf Odselius, Hakan Pertoft, Göran ÅkerströmAbstract: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.
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impaired Parathyroid Hormone Release in human immunodeficiency virus infection
AIDS Research and Human Retroviruses, 1994Co-Authors: Per Hellman, Jonas Rastad, Göran Åkerström, Jan Albert, Magnus Gidlund, Lars Klareskog, Claes JuhlinAbstract:Patients with human immunodeficiency virus type 1 (HIV-1) seropositivity exhibited significantly lower intact serum Parathyroid Hormone (PTH) values (mean, 13.6 ng/liter; n = 44) than healthy controls (mean, 38.1 ng/liter; p 400 x 10(6) CD4+ lymphocytes/ml blood; n = 22) than in those with severe immunodeficiency (< 200 x 10(6) CD4+ lymphocytes/ml blood; n 22; p = 0.03), although total serum calcium was normal in all groups. Patients with severe immunodeficiency demonstrated an inverse correlation between total serum calcium and serum PTH (r2 = 0.367; p < 0.01), which was also present in healthy controls (r2 = 0.482; p < 0.001), but not among the seropositive patients with no or mild immunodeficiency (r2 = 0.017; p = 0.58). Parathyroid cells express a protein recognized by antibodies directed against CD4, the HIV-1 receptor. This implies that these cells may be directly infected with HIV-1 and also interact with circulating autoantibodies against CD4, thus resulting in impaired PTH Release.
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ga3 inhibits Parathyroid Hormone Release without interacting with the ca2 receptor of the Parathyroid cell
Biochemical and Biophysical Research Communications, 1992Co-Authors: Peter Ridefelt, Jonas Rastad, Göran Åkerström, Sverker Ljunghall, Per Hellman, Osten Ljunggren, Erik GylfeAbstract:Gallium nitrate is an antihypercalcemic agent with established actions on bone. The effects of Ga(N03)3 on Parathyroid Hormone (PTH) Release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP production of enzymatically dispersed Parathyroid cells from bovine as well as normal and pathological human Parathyroid glands have now been studied. Ga3+ at 200 μM inhibited PTH Release whereas 600 μM NO3 had no effect. The inhibition was additive to that obtained by elevating extracellular Ca2+. Unlike Ca2+, Ga3+ failed to increase [Ca2+]i or reduce cAMP formation. The results indicate that Ga3+ inhibits PTH Release by a mechanism other than activation of the cation receptor of the Parathyroid cells. This mechanism may contribute also to inhibition by other cations.
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dynamics of Parathyroid Hormone Release and serum calcium regulation after surgery for primary hyperParathyroidism
World Journal of Surgery, 1992Co-Authors: Wilhelm Graf, Jonas Rastad, Göran Åkerström, Leif Wide, Sverker LjunghallAbstract:Analysis of 14 patients with primary hyperParathyroidism (HPT) prior to and during the first year after Parathyroid surgery disclosed that the operation was associated with rapid reductions of intact serum Parathyroid Hormone (PTH) and total serum and ionized plasma calcium values. A decreased urinary calcium excretion, a gradual elevation of renal calcium reabsorption, a transient reduction of serum calcitriol, and a late increase in 25-hydroxycholecalciferol values were also noted. Dynamic tests of Parathyroid function by EDTA infusion and an oral calcium load revealed a sigmoidal relationship between serum PTH and calcium levels, and that Parathyroid surgery induced considerable changes in both the position and slope of the dose-response curve. It was also apparent that PTH Release was submaximally stimulated event at periods of hypocalcemia. The findings substantiate that adjustments of PTH Release to acute alterations of serum calcium occur along the prevailing dose-response relationship, while stimuli being maintained for longer periods of time induce compensatory shifts in the position and slope of this curve. It is further suggested that unknown factors with PTH-like function may participate in the calcium regulation after surgery for primary HPT.
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regulation of Parathyroid Hormone Release in normal and pathological Parathyroid cells exposed to modulators of protein kinase c
European Journal of Endocrinology, 1992Co-Authors: Peter Ridefelt, Rolf Larsson, Jonas Rastad, Peter Nygren, Göran Åkerström, Per Hellman, Erik GylfeAbstract:Effects of the protein kinase C activating phorbol ester 12-O-tetradecanoyl phorbol 13-acetate and the inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) on Parathyroid Hormone (PTH) Release were studied in normal bovine and pathological human Parathyroid cells. An increase of extracellular Ca2+ from 0.5 to 3.0 mmol/l inhibited PTH Release by 60% in the bovine cells with half maximal effect (ED50) at 1.31 mmol/l. This inhibition reached less than 50% in the cells from patients with primary and uremic hyperParathyroidism, and the ED50 values were 1.49 and 1.42 mmol/l, respectively. The phorbol ester (0.1 mumol/l) made secretion insensitive to changes of extracellular Ca2+, an action counteracted by H-7 (50 mumol/l) in the bovine cells, whereas H-7 alone had no effects. The phorbol ester and H-7 had opposite actions on regulation of PTH Release also from cells from patients with hyperParathyroidism. However, in pathological cells H-7 alone improved Ca2+ inhibition of secretion by stimulating Release in low Ca2+ concentrations and decreasing the ED50 values. The magnitude of changes in ED50 values by H-7 increased with the severity of the secretory disturbance of the pathological cells. The results indicate that increased protein kinase C activity may be a factor of importance in the pathophysiology of hyperParathyroidism.
William G Goodman - One of the best experts on this subject based on the ideXlab platform.
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suppressive effect of calcium on Parathyroid Hormone Release in adynamic renal osteodystrophy and secondary hyperParathyroidism
Kidney International, 1997Co-Authors: Johannes D. Veldhuis, William G Goodman, Thomas R Belin, Harald JuppnerAbstract:Suppressive effect of calcium on Parathyroid Hormone Release in adynamic renal osteodystrophy and secondary hyperParathyroidism. Serum Parathyroid Hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperParathyroidism (2°HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and Parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH Release in AD and in 2°HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2°HPT and in 20NL. Basal serum PTH levels were 88 ± 51, 536 ± 395, and 26 ± 6 pg/ml, respectively, in AD, 2°HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 ± 5.6%)and in 2°HPT (27.8 ± 12.3%) than in NL, (11.9 ± 5.8%, P −1 ) in serum PTH were less in AD and 2°HPT than in NL, P −1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031min −1 (0.025 to 0.036) in 2°HPT and 87% (84 to 89) and 0.070min −1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2°HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P r = 0.90 and P r = 0.75 and P P χ 2 = 17.81, P in vivo does not differ in AD and 2°HPT despite marked differences in basal serum PTH levels. Variations in functional Parathyroid gland mass rather than disturbances in calcium-sensing by the Parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2°HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.
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suppressive effect of calcium on Parathyroid Hormone Release in adynamic renal osteodystrophy and secondary hyperParathyroidism
Kidney International, 1997Co-Authors: Johannes D. Veldhuis, William G Goodman, Thomas R Belin, Harald JuppnerAbstract:Serum Parathyroid Hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperParathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and Parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH Release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH Release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional Parathyroid gland mass rather than disturbances in calcium-sensing by the Parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.
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in vivo assessments of calcium regulated Parathyroid Hormone Release in secondary hyperParathyroidism
Kidney International, 1996Co-Authors: William G Goodman, Thomas R Belin, Isidro B SaluskyAbstract:In vivo dynamic tests of Parathyroid gland function have provided useful information about the secretory behavior of Parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of Parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary hyperParathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed Parathyroid cells from patients with primary hyperParathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of Parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of Parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH Release is abnormal in secondary hyperParathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH Release in patients with uremic secondary hyperParathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of secondary hyperParathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH Release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of Parathyroid hyperplasia and the role of factors that influence the development of Parathyroid gland enlargement may ultimately prove to be particularly important modifiers of Parathyroid gland function in chronic renal failure.
-
calcium regulated Parathyroid Hormone Release in patients with mild or advanced secondary hyperParathyroidism
Kidney International, 1995Co-Authors: William G Goodman, Thomas R Belin, Harald Juppner, Barbara Gales, Gino V Segre, Isidro B SaluskyAbstract:Calcium-regulated Parathyroid Hormone Release in patients with mild or advanced secondary hyperParathyroidism. Differences in the regulation of Parathyroid Hormone (PTH) Release by calcium are thought to account for excess PTH secretion in patients with secondary hyperParathyroidism (2°HPTH). To determine whether calcium-regulated PTH Release varies with the severity of 2°HPTH in patients with end-stage renal disease, dynamic tests of Parathyroid gland function were done using the four-parameter model in 26 patients with 2°HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH 600 pg/ml) 2°HPTH; values were 1.23 ± 0.06 mmol/liter, 1.24 ± 0.06 mmol/liter and 1.23 ± 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 ± 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2°HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P in vivo dynamic tests of Parathyroid gland function. The results suggest that variations in Parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.
Jonas Rastad - One of the best experts on this subject based on the ideXlab platform.
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alteration in density morphology and Parathyroid Hormone Release of dispersed Parathyroid cells from patients with hyperParathyroidism
Apmis, 2009Co-Authors: Claes Rudberg, Jonas Rastad, Sverker Ljunghall, Leif Wide, Lars Grimelius, Henry Johansson, Rolf Odselius, Hakan Pertoft, Göran ÅkerströmAbstract: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.
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impaired Parathyroid Hormone Release in human immunodeficiency virus infection
AIDS Research and Human Retroviruses, 1994Co-Authors: Per Hellman, Jonas Rastad, Göran Åkerström, Jan Albert, Magnus Gidlund, Lars Klareskog, Claes JuhlinAbstract:Patients with human immunodeficiency virus type 1 (HIV-1) seropositivity exhibited significantly lower intact serum Parathyroid Hormone (PTH) values (mean, 13.6 ng/liter; n = 44) than healthy controls (mean, 38.1 ng/liter; p 400 x 10(6) CD4+ lymphocytes/ml blood; n = 22) than in those with severe immunodeficiency (< 200 x 10(6) CD4+ lymphocytes/ml blood; n 22; p = 0.03), although total serum calcium was normal in all groups. Patients with severe immunodeficiency demonstrated an inverse correlation between total serum calcium and serum PTH (r2 = 0.367; p < 0.01), which was also present in healthy controls (r2 = 0.482; p < 0.001), but not among the seropositive patients with no or mild immunodeficiency (r2 = 0.017; p = 0.58). Parathyroid cells express a protein recognized by antibodies directed against CD4, the HIV-1 receptor. This implies that these cells may be directly infected with HIV-1 and also interact with circulating autoantibodies against CD4, thus resulting in impaired PTH Release.
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ga3 inhibits Parathyroid Hormone Release without interacting with the ca2 receptor of the Parathyroid cell
Biochemical and Biophysical Research Communications, 1992Co-Authors: Peter Ridefelt, Jonas Rastad, Göran Åkerström, Sverker Ljunghall, Per Hellman, Osten Ljunggren, Erik GylfeAbstract:Gallium nitrate is an antihypercalcemic agent with established actions on bone. The effects of Ga(N03)3 on Parathyroid Hormone (PTH) Release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP production of enzymatically dispersed Parathyroid cells from bovine as well as normal and pathological human Parathyroid glands have now been studied. Ga3+ at 200 μM inhibited PTH Release whereas 600 μM NO3 had no effect. The inhibition was additive to that obtained by elevating extracellular Ca2+. Unlike Ca2+, Ga3+ failed to increase [Ca2+]i or reduce cAMP formation. The results indicate that Ga3+ inhibits PTH Release by a mechanism other than activation of the cation receptor of the Parathyroid cells. This mechanism may contribute also to inhibition by other cations.
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dynamics of Parathyroid Hormone Release and serum calcium regulation after surgery for primary hyperParathyroidism
World Journal of Surgery, 1992Co-Authors: Wilhelm Graf, Jonas Rastad, Göran Åkerström, Leif Wide, Sverker LjunghallAbstract:Analysis of 14 patients with primary hyperParathyroidism (HPT) prior to and during the first year after Parathyroid surgery disclosed that the operation was associated with rapid reductions of intact serum Parathyroid Hormone (PTH) and total serum and ionized plasma calcium values. A decreased urinary calcium excretion, a gradual elevation of renal calcium reabsorption, a transient reduction of serum calcitriol, and a late increase in 25-hydroxycholecalciferol values were also noted. Dynamic tests of Parathyroid function by EDTA infusion and an oral calcium load revealed a sigmoidal relationship between serum PTH and calcium levels, and that Parathyroid surgery induced considerable changes in both the position and slope of the dose-response curve. It was also apparent that PTH Release was submaximally stimulated event at periods of hypocalcemia. The findings substantiate that adjustments of PTH Release to acute alterations of serum calcium occur along the prevailing dose-response relationship, while stimuli being maintained for longer periods of time induce compensatory shifts in the position and slope of this curve. It is further suggested that unknown factors with PTH-like function may participate in the calcium regulation after surgery for primary HPT.
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regulation of Parathyroid Hormone Release in normal and pathological Parathyroid cells exposed to modulators of protein kinase c
European Journal of Endocrinology, 1992Co-Authors: Peter Ridefelt, Rolf Larsson, Jonas Rastad, Peter Nygren, Göran Åkerström, Per Hellman, Erik GylfeAbstract:Effects of the protein kinase C activating phorbol ester 12-O-tetradecanoyl phorbol 13-acetate and the inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) on Parathyroid Hormone (PTH) Release were studied in normal bovine and pathological human Parathyroid cells. An increase of extracellular Ca2+ from 0.5 to 3.0 mmol/l inhibited PTH Release by 60% in the bovine cells with half maximal effect (ED50) at 1.31 mmol/l. This inhibition reached less than 50% in the cells from patients with primary and uremic hyperParathyroidism, and the ED50 values were 1.49 and 1.42 mmol/l, respectively. The phorbol ester (0.1 mumol/l) made secretion insensitive to changes of extracellular Ca2+, an action counteracted by H-7 (50 mumol/l) in the bovine cells, whereas H-7 alone had no effects. The phorbol ester and H-7 had opposite actions on regulation of PTH Release also from cells from patients with hyperParathyroidism. However, in pathological cells H-7 alone improved Ca2+ inhibition of secretion by stimulating Release in low Ca2+ concentrations and decreasing the ED50 values. The magnitude of changes in ED50 values by H-7 increased with the severity of the secretory disturbance of the pathological cells. The results indicate that increased protein kinase C activity may be a factor of importance in the pathophysiology of hyperParathyroidism.
Thomas R Belin - One of the best experts on this subject based on the ideXlab platform.
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suppressive effect of calcium on Parathyroid Hormone Release in adynamic renal osteodystrophy and secondary hyperParathyroidism
Kidney International, 1997Co-Authors: Johannes D. Veldhuis, William G Goodman, Thomas R Belin, Harald JuppnerAbstract:Suppressive effect of calcium on Parathyroid Hormone Release in adynamic renal osteodystrophy and secondary hyperParathyroidism. Serum Parathyroid Hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperParathyroidism (2°HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and Parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH Release in AD and in 2°HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2°HPT and in 20NL. Basal serum PTH levels were 88 ± 51, 536 ± 395, and 26 ± 6 pg/ml, respectively, in AD, 2°HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 ± 5.6%)and in 2°HPT (27.8 ± 12.3%) than in NL, (11.9 ± 5.8%, P −1 ) in serum PTH were less in AD and 2°HPT than in NL, P −1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031min −1 (0.025 to 0.036) in 2°HPT and 87% (84 to 89) and 0.070min −1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2°HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P r = 0.90 and P r = 0.75 and P P χ 2 = 17.81, P in vivo does not differ in AD and 2°HPT despite marked differences in basal serum PTH levels. Variations in functional Parathyroid gland mass rather than disturbances in calcium-sensing by the Parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2°HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.
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suppressive effect of calcium on Parathyroid Hormone Release in adynamic renal osteodystrophy and secondary hyperParathyroidism
Kidney International, 1997Co-Authors: Johannes D. Veldhuis, William G Goodman, Thomas R Belin, Harald JuppnerAbstract:Serum Parathyroid Hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperParathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and Parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH Release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH Release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional Parathyroid gland mass rather than disturbances in calcium-sensing by the Parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.
-
in vivo assessments of calcium regulated Parathyroid Hormone Release in secondary hyperParathyroidism
Kidney International, 1996Co-Authors: William G Goodman, Thomas R Belin, Isidro B SaluskyAbstract:In vivo dynamic tests of Parathyroid gland function have provided useful information about the secretory behavior of Parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of Parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary hyperParathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed Parathyroid cells from patients with primary hyperParathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of Parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of Parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH Release is abnormal in secondary hyperParathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH Release in patients with uremic secondary hyperParathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of secondary hyperParathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH Release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of Parathyroid hyperplasia and the role of factors that influence the development of Parathyroid gland enlargement may ultimately prove to be particularly important modifiers of Parathyroid gland function in chronic renal failure.
-
calcium regulated Parathyroid Hormone Release in patients with mild or advanced secondary hyperParathyroidism
Kidney International, 1995Co-Authors: William G Goodman, Thomas R Belin, Harald Juppner, Barbara Gales, Gino V Segre, Isidro B SaluskyAbstract:Calcium-regulated Parathyroid Hormone Release in patients with mild or advanced secondary hyperParathyroidism. Differences in the regulation of Parathyroid Hormone (PTH) Release by calcium are thought to account for excess PTH secretion in patients with secondary hyperParathyroidism (2°HPTH). To determine whether calcium-regulated PTH Release varies with the severity of 2°HPTH in patients with end-stage renal disease, dynamic tests of Parathyroid gland function were done using the four-parameter model in 26 patients with 2°HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH 600 pg/ml) 2°HPTH; values were 1.23 ± 0.06 mmol/liter, 1.24 ± 0.06 mmol/liter and 1.23 ± 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 ± 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2°HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P in vivo dynamic tests of Parathyroid gland function. The results suggest that variations in Parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.
Erik Gylfe - One of the best experts on this subject based on the ideXlab platform.
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ga3 inhibits Parathyroid Hormone Release without interacting with the ca2 receptor of the Parathyroid cell
Biochemical and Biophysical Research Communications, 1992Co-Authors: Peter Ridefelt, Jonas Rastad, Göran Åkerström, Sverker Ljunghall, Per Hellman, Osten Ljunggren, Erik GylfeAbstract:Gallium nitrate is an antihypercalcemic agent with established actions on bone. The effects of Ga(N03)3 on Parathyroid Hormone (PTH) Release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP production of enzymatically dispersed Parathyroid cells from bovine as well as normal and pathological human Parathyroid glands have now been studied. Ga3+ at 200 μM inhibited PTH Release whereas 600 μM NO3 had no effect. The inhibition was additive to that obtained by elevating extracellular Ca2+. Unlike Ca2+, Ga3+ failed to increase [Ca2+]i or reduce cAMP formation. The results indicate that Ga3+ inhibits PTH Release by a mechanism other than activation of the cation receptor of the Parathyroid cells. This mechanism may contribute also to inhibition by other cations.
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regulation of Parathyroid Hormone Release in normal and pathological Parathyroid cells exposed to modulators of protein kinase c
European Journal of Endocrinology, 1992Co-Authors: Peter Ridefelt, Rolf Larsson, Jonas Rastad, Peter Nygren, Göran Åkerström, Per Hellman, Erik GylfeAbstract:Effects of the protein kinase C activating phorbol ester 12-O-tetradecanoyl phorbol 13-acetate and the inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) on Parathyroid Hormone (PTH) Release were studied in normal bovine and pathological human Parathyroid cells. An increase of extracellular Ca2+ from 0.5 to 3.0 mmol/l inhibited PTH Release by 60% in the bovine cells with half maximal effect (ED50) at 1.31 mmol/l. This inhibition reached less than 50% in the cells from patients with primary and uremic hyperParathyroidism, and the ED50 values were 1.49 and 1.42 mmol/l, respectively. The phorbol ester (0.1 mumol/l) made secretion insensitive to changes of extracellular Ca2+, an action counteracted by H-7 (50 mumol/l) in the bovine cells, whereas H-7 alone had no effects. The phorbol ester and H-7 had opposite actions on regulation of PTH Release also from cells from patients with hyperParathyroidism. However, in pathological cells H-7 alone improved Ca2+ inhibition of secretion by stimulating Release in low Ca2+ concentrations and decreasing the ED50 values. The magnitude of changes in ED50 values by H-7 increased with the severity of the secretory disturbance of the pathological cells. The results indicate that increased protein kinase C activity may be a factor of importance in the pathophysiology of hyperParathyroidism.
