The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Guy Bisson - One of the best experts on this subject based on the ideXlab platform.
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preoperative localization of parathyroid lesions in hyperparathyroidism relationship between technetium 99m mibi uptake and Oxyphil cell content
The Journal of Nuclear Medicine, 1998Co-Authors: Andre C Carpentier, Guy Bisson, Simon Jeannotte, Jean Verreault, Bernard Lefebvre, Charlesjacques Mongeau, Pierre MaheuxAbstract:UNLABELLED The aim of this study was to assess the relationship between parathyroid Oxyphil cell content and early or late phases of uptake of 99mTc-MIBI, a radioisotope preferentially retained in mitochondria-rich Cells. METHODS This study is a retrospective, single-blind analysis of all double-phase 99mTc-MIBI parathyroid scintigraphy studies performed before surgery in our institution between 1990 and 1995. A total of 18 parathyroid lesions in 14 patients were reviewed. This sample included 11 cases of primary hyperparathyroidism (8 adenomas, 1 adenocarcinoma and 2 hyperplasias) and 3 cases of tertiary hyperparathyroidism secondary to chronic renal failure. RESULTS Uptake of 99mTc-MIBI in the early phase of scintigraphy was associated with larger parathyroid lesions (1.61 +/- 1.61 ml versus 0.33 +/- 0.27 ml; p < 0.02) and higher serum calcium levels (3.00 +/- 0.41 mM versus 2.67 +/- 0.14 mM; p < 0.02). More importantly, we found that a parathyroid Oxyphil cell content greater than 25% was more often associated with a positive uptake of 99mTc-MIBI in the late phase of the test (positive late uptake in 78% of lesions with a high Oxyphil cell content versus 33% in lesions with an Oxyphil cell content between 1% and 25% and 0% in lesions with no Oxyphil Cells; p < 0.04). CONCLUSION These findings suggest that the late retention of 99mTc-MIBI in double-phase scintigraphy is related to parathyroid Oxyphil cell content.
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rapid washout of technetium 99m mibi from a large parathyroid adenoma
The Journal of Nuclear Medicine, 1995Co-Authors: Francois Benard, Mariefrance Langlois, F Beuvon, B Lefebvre, Guy BissonAbstract:The authors report a case of rapid {sup 99m}Tc-methoxyisobutylisonitrile (MIBI) clearance from a parathyroid adenoma. A double-phase {sup 99m}Tc-MIBI parathyroid scintigraphy was performed on a 62-yr-old female evaluated for primary hyperparathyroidism. A large parathyroid adenoma was visualized caudal to the left lobe of the thyroid gland with an unusually rapid washout of the tracer from tumor tissue. Histologic tissue examination confirmed the presence of a parathyroid adenoma and the absence of Oxyphil Cells. Care should be taken in interpretation of {sup 99m}Tc-MiBI parathyroid scintigrams because some adenomas can present a rapid release of the radiotracer in a double-phase study. Technitium-99m-MIBI retention could be related to the number of mitochondria-rich Cells in parathyroid adenomas or to hyperplasia. 7 refs., 2 figs.
Won Woo Lee - One of the best experts on this subject based on the ideXlab platform.
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the usefulness of maximum standardized uptake value at the delayed phase of tc 99m sestamibi single photon emission computed tomography computed tomography for identification of parathyroid adenoma and hyperplasia
Medicine, 2020Co-Authors: Hoon Young Suh, So Yeon Park, June Young Choi, Won Woo LeeAbstract:Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism.Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 ± 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief Cells, Oxyphil Cells, and clear Cells.SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 ± 6.68, 7.90 ± 5.49, and 7.01 ± 2.62 at 10min (early phase), decreasing to 7.46 ± 5.66, 4.65 ± 3.14, and 2.21 ± 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P < .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of Oxyphil Cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant Oxyphil Cells (rho = 0.418, P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions.SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.
Alex J Brown - One of the best experts on this subject based on the ideXlab platform.
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paricalcitol and cinacalcet have disparate actions on parathyroid Oxyphil cell content in patients with chronic kidney disease
Kidney International, 2017Co-Authors: Cynthia S Ritter, Alex J Brown, Brent W. Miller, Daniel W Coyne, Diptesh Gupta, Sijie Zheng, Eduardo SlatopolskyAbstract:The parathyroid Oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil Cells have significantly more calcium-sensing receptors than chief Cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an Oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the Oxyphil cell content in patients with CKD to further investigate the genesis of these Cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid Oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-Oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.
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differential gene expression by Oxyphil and chief Cells of human parathyroid glands
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Cynthia S Ritter, Brent W. Miller, Bruce H Haughey, Alex J BrownAbstract:Context: Parathyroid Oxyphil Cells, whose function is unknown, are thought to be derived from chief Cells. Oxyphil Cells increase in number in parathyroid glands of patients with chronic kidney disease (CKD) and are even more abundant in patients receiving treatment for hyperparathyroidism with calcitriol and/or the calcimimetic cinacalcet. Objective: We examined Oxyphil and chief Cells of parathyroid glands of CKD patients for differential expression of genes important to parathyroid function. Design/Setting/Participants: Parathyroid tissue from CKD patients with refractory hyperparathyroidism was immunostained for gene expression studies. Main Outcome Measure: Immunostaining for PTH, PTHrP, calcium-sensing receptor, glial Cells missing 2, vitamin D receptor, 25-hydroxyvitamin D-1α-hydroxylase, and cytochrome c was quantified and expression reported for Oxyphil and chief Cells. Results: Expression of all proteins analyzed, except for the vitamin D receptor, was higher in Oxyphil Cells than in chief Cells...
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distribution and regulation of the 25 hydroxyvitamin d3 1α hydroxylase in human parathyroid glands
The Journal of Steroid Biochemistry and Molecular Biology, 2012Co-Authors: Cynthia S Ritter, Bruce H Haughey, Harvey J Armbrecht, Alex J BrownAbstract:Abstract Parathyroid glands express the 25-hydroxyvitamin D3 1α-hydroxylase (1αOHase). 1,25-dihydroxyvitamin D3 (calcitriol) synthesized by extrarenal tissues generally does not enter the circulation, but plays an autocrine/paracrine role specific to the cell type, and is regulated by the needs of that particular cell. While the role of calcitriol produced in the parathyroid glands presumably is to suppress PTH and cell growth, its regulation in this cell type has not been defined. In the present study, we found that regulation of the human parathyroid 1αOHase differs from the renal enzyme in that it is induced by FGF-23 and extracellular calcium. Hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. We found that the 1αOHase is expressed at much higher levels in Oxyphil Cells than in chief Cells in these patients. Recent findings indicate that Oxyphil cell content is increased by treatment with calcium receptor activators (calcimimetics). Here, we demonstrate that the calcimimetic cinacalcet increases the expression of 1αOHase in human parathyroid cultures. Additionally, we found that the 1αOHase in human parathyroid cultures is functionally active, as evidenced by the ability of the enzyme to 1-hydroxylate 25(OH)D3 in parathyroid monolayers. Calcium, as well as cinacalcet, also induced expression of the degradation enzyme 24-hydroxylase, indicating the presence of a negative feedback system in the parathyroid Cells. Therefore, local production of 1αOHase suggests an autocrine/paracrine role in regulating parathyroid function and may mediate, in part, the suppression of PTH by calcium and FGF-23.
J Mullerhocker - One of the best experts on this subject based on the ideXlab platform.
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expression of bcl 2 bax and fas in Oxyphil Cells of hashimoto thyroiditis
Virchows Archiv, 2000Co-Authors: J MullerhockerAbstract:Immunoreactivity for bcl-2, Bax and Fas was analysed in 16 cases with Hashimoto thyroiditis. Bcl-2-expression was constantly seen in regular thyrocytes and in the mantle-zone of lymphofollicular infiltrates. However, thyrocytes in the vicinity of lymphoid infiltrates and, especially, mitochondria-rich Oxyphil Cells exhibited reduced staining or none at all for bcl-2. Bax was found to be weakly reactive or negative in normal thyrocytes and was not up-regulated in bcl-2-deficient epithelial Cells. In contrast, expression of Fas was markedly increased both in typical thyrocytes and in Oxyphil Cells within areas of lymphocytic infiltration. In conclusion, focal lack of bcl-2 expression together with up-regulation of Fas is a constant feature of Hashimoto thyroiditis. The reaction pattern of Oxyphil Cells is identical to that of affected typical thyrocytes without proliferation of mitochondria. Loss of bcl-2 with up-regulation of Fas is therefore likely to precede oncocytic change. Whether these alterations are involved in the process of oncocytic transformation remains to be clarified, however.
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immunohistochemical detection of human mtdna polymerase gamma and of human mitochondrial transcription factor a in cytochrome c oxidase deficient Oxyphil Cells of hyperfunctional parathyroids
Virchows Archiv, 1998Co-Authors: J Mullerhocker, S Schafer, William C Copeland, R Wiesner, Peter SeibelAbstract:Immunohistochemical studies were performed in 18 hyperfunctional parathyroids with Oxyphil cell aggregates for the detection of cytochrome-c-oxidase (complex IV of the respiratory chain), mitochondrial DNA polymerase gamma and human mitochondrial transcription factor A (h-mtTFA). Seventy-three Oxyphil areas exhibiting a defect of cytochrome-c-oxidase were found. The defect involved both the mitochondrially coded subunits II/III and the nuclear derived subunits Vab. There was no loss of mtDNA polymerase gamma or of h-mtTFA in these foci, corresponding to a high content of mtDNA revealed by in situ hybridization. Isolated defects of h-mtTFA were also not found. In contrast, isolated defects of mtDNA polymerase gamma were present in 22 Oxyphil foci. These results show that defects of cytochrome-c-oxidase in Oxyphil Cells are not due to altered expression of h-mtTFA or DNA polymerase gamma, indicating that other nuclear factors involved in the generation of the respiratory chain may be impaired. The low incidence of defects of mtDNA polymerase gamma and the absence of alterations of h-mtTFA and cytochrome-c-oxidase in these foci suggest that defects of mtDNA polymerase gamma are of minor pathogenetic significance.
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hashimoto thyroiditis is associated with defects of cytochrome c oxidase in Oxyphil askanazy Cells and with the common deletion 4 977 of mitochondrial dna
Ultrastructural Pathology, 1998Co-Authors: J Mullerhocker, U Jacob, Peter SeibelAbstract:The activity of cytochrome-c oxidase, the terminal enzyme of the respiratory chain (complex IV), was studied at the ultrastructural level in a case of Hashimoto thyroiditis. Cytochrome-c oxidase showed a heterogeneous reaction pattern in Oxyphil Cells, with scattered foci of Oxyphil Cells lacking cytochrome-c oxidase staining. In most of the Cells the defect involved all the mitochondria, but there were also Oxyphil Cells with a heterogeneous mitochondrial population characterized by an intracellular coexistence of mitochondria with either intact cytochrome-c oxidase or lacking activity. Immunocytochemistry further disclosed loss of mitochondrially and nuclearly encoded subunits of the enzyme. Molecular genetic analysis of mitochondrial DNA (mtDNA) revealed the presence of the 4977 base pair deletion ("common deletion") of mtDNA (8,482-13,459) in the affected areas but not in normal thyroid tissue of the patient. The amount of deleted mtDNA varied between 2 and 8% of total mtDNA. The results demonstrate that Oxyphil cell change in Hashimoto thyroiditis is associated with functional and molecular genetic defects of the respiratory chain.
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defects of the respiratory chain in Oxyphil and chief Cells of the normal parathyroid and in hyperfunction
Human Pathology, 1996Co-Authors: J Mullerhocker, Peter Seibel, D Aust, J Napiwotzky, Ch Munscher, Th A Link, Sebastian Schneeweiss, Bernhard KadenbachAbstract:Abstract Immunohistochemical detection of complex III (ubiquinone-cytochrome-c-oxidore-ductase) and complex IV (cytochrome-c-oxidase) of the respiratory chain was performed in parathyroids of 164 humans with normal renal function (group I) and in 55 patients with chronic renal insufficiency (group II) obtained at autopsy. In group I, 33 of the 164 cases showed defects of the respiratory chain (20%). Eighty-five percent of the defects occurred in advanced age (>50 years). In group II, 39 of 55 cases (70%) had defects, and about 70% of the defects occurred after age 50. In both groups, more than 80% of the defects were localized in Oxyphil cell nodules. However, not every Oxyphil nodule was involved. In group I, selective defects of complex IV predominated and were found in 47 of 86 defects (55%). Combined defects of complexes III and IV were present in 25 of 86 defects (29%). In contrast, in group II combined defects predominated and were found in 45% (107 of 240 defects), whereas single defects of complex IV existed in 38% (93 of 240 defects). The frequency of selective defects of complex III was about 16% to 17% in both groups. In situ hybridization and PCR studies for the detection of the common deletion (4.977 base pairs) and of various point mutations of mitochondrial of (m)DNA revealed no consistent molecular genetic abnormalities. A point mutation in the tRNA Leu(UUR) at nucleotide (nt) 3.260 was found in only one probe. The results show that defects of the respiratory chain occur already in normal parathyroids, most probably during cell aging, especially in Oxyphil Cells and at a higher rate in hyperfunction. The high predominance of respiratory chain defects in Oxyphil Cells and their random distribution favors mutations of mtDNA as a possible cause of Oxyphilic cell transformation and of the respiratory chain defects. However, the mutations of mtDNA in the parathyroids are apparently different from those in other ageing tissues.
Cynthia S Ritter - One of the best experts on this subject based on the ideXlab platform.
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paricalcitol and cinacalcet have disparate actions on parathyroid Oxyphil cell content in patients with chronic kidney disease
Kidney International, 2017Co-Authors: Cynthia S Ritter, Alex J Brown, Brent W. Miller, Daniel W Coyne, Diptesh Gupta, Sijie Zheng, Eduardo SlatopolskyAbstract:The parathyroid Oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil Cells have significantly more calcium-sensing receptors than chief Cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an Oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the Oxyphil cell content in patients with CKD to further investigate the genesis of these Cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid Oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-Oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.
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differential gene expression by Oxyphil and chief Cells of human parathyroid glands
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Cynthia S Ritter, Brent W. Miller, Bruce H Haughey, Alex J BrownAbstract:Context: Parathyroid Oxyphil Cells, whose function is unknown, are thought to be derived from chief Cells. Oxyphil Cells increase in number in parathyroid glands of patients with chronic kidney disease (CKD) and are even more abundant in patients receiving treatment for hyperparathyroidism with calcitriol and/or the calcimimetic cinacalcet. Objective: We examined Oxyphil and chief Cells of parathyroid glands of CKD patients for differential expression of genes important to parathyroid function. Design/Setting/Participants: Parathyroid tissue from CKD patients with refractory hyperparathyroidism was immunostained for gene expression studies. Main Outcome Measure: Immunostaining for PTH, PTHrP, calcium-sensing receptor, glial Cells missing 2, vitamin D receptor, 25-hydroxyvitamin D-1α-hydroxylase, and cytochrome c was quantified and expression reported for Oxyphil and chief Cells. Results: Expression of all proteins analyzed, except for the vitamin D receptor, was higher in Oxyphil Cells than in chief Cells...
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distribution and regulation of the 25 hydroxyvitamin d3 1α hydroxylase in human parathyroid glands
The Journal of Steroid Biochemistry and Molecular Biology, 2012Co-Authors: Cynthia S Ritter, Bruce H Haughey, Harvey J Armbrecht, Alex J BrownAbstract:Abstract Parathyroid glands express the 25-hydroxyvitamin D3 1α-hydroxylase (1αOHase). 1,25-dihydroxyvitamin D3 (calcitriol) synthesized by extrarenal tissues generally does not enter the circulation, but plays an autocrine/paracrine role specific to the cell type, and is regulated by the needs of that particular cell. While the role of calcitriol produced in the parathyroid glands presumably is to suppress PTH and cell growth, its regulation in this cell type has not been defined. In the present study, we found that regulation of the human parathyroid 1αOHase differs from the renal enzyme in that it is induced by FGF-23 and extracellular calcium. Hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. We found that the 1αOHase is expressed at much higher levels in Oxyphil Cells than in chief Cells in these patients. Recent findings indicate that Oxyphil cell content is increased by treatment with calcium receptor activators (calcimimetics). Here, we demonstrate that the calcimimetic cinacalcet increases the expression of 1αOHase in human parathyroid cultures. Additionally, we found that the 1αOHase in human parathyroid cultures is functionally active, as evidenced by the ability of the enzyme to 1-hydroxylate 25(OH)D3 in parathyroid monolayers. Calcium, as well as cinacalcet, also induced expression of the degradation enzyme 24-hydroxylase, indicating the presence of a negative feedback system in the parathyroid Cells. Therefore, local production of 1αOHase suggests an autocrine/paracrine role in regulating parathyroid function and may mediate, in part, the suppression of PTH by calcium and FGF-23.
