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Sample records for association determines parathyroid

  1. Association of parathyroid carcinoma and thyroid disorders: A clinical review.

    PubMed

    Campennì, Alfredo; Giovinazzo, Salvatore; Pignata, Salvatore Antonio; Di Mauro, Francesca; Santoro, Domenico; Curtò, Lorenzo; Trimarchi, Francesco; Ruggeri, Rosaria Maddalena; Baldari, Sergio

    2017-04-01

    Parathyroid carcinoma is a rare malignancy, which usually occurs as a sporadic disease, and less frequently in the setting of genetic syndromes. Despite the association of parathyroid and thyroid disorders being quite common, the coexistence of parathyroid carcinoma and thyroid disease is rare. We reviewed the pertinent literature. The terms "parathyroid carcinoma" and "thyroid disease, hyperthyroidism, thyrotoxicosis, hypothyroidism, thyroid nodule(s), Graves' disease, autonomously functioning thyroid nodules" were used both separately and in reciprocal conjunction to search MEDLINE for articles published from January 2007 to March 2016. The search was prompted by the observation of a never reported association of autonomously functioning thyroid nodules and parathyroid carcinoma. Two hundred and twenty-one parathyroid carcinoma patients have been described during the last 10 years. Neck ultrasonography and parathyroid scintigraphy are the most common instrumental studies used in detecting parathyroid lesions. Serum parathyroid hormone and calcium levels are high in the majority of parathyroid carcinoma patients. Only 21 patients with parathyroid carcinoma and thyroid disorders were found. Our patient is the first casual association between parathyroid carcinoma and autonomously functioning thyroid nodules reported in literature and diagnosed using parathyroid and thyroid scintigraphies. Parathyroid carcinoma is a very rare endocrine tumor and association with thyroid disease is not frequent. Parathyroid carcinoma pre-operative diagnosis is often difficult also because available literature data are not homogenous and there is not a common operative guideline. Our case confirms the role of parathyroid scintigraphy, encouraging the association with thyroid scintigraphy, especially in the presence of (multi)-nodular goiter in order to address the most appropriate surgical management.

  2. Genetic Variants Associated with Circulating Parathyroid Hormone.

    PubMed

    Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

    2016-12-07

    Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10(-53)), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10(-17)), rs219779 adjacent to CLDN14 (P=3.5 × 10(-16)), rs4443100 near RTDR1 (P=8.7 × 10(-9)), and rs73186030 near CASR (P=4.8 × 10(-8)). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

  3. Parathyroid hyperplasia

    MedlinePlus

    Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic kidney disease - parathyroid hyperplasia; ...

  4. Parathyroid adenoma

    MedlinePlus

    Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... Parathyroid adenomas are the most common cause of hyperparathyroidism (overactive parathyroid glands), which leads to an increased ...

  5. DETERMINANTS OF PLASMA PARATHYROID HORMONE LEVELS IN YOUNG WOMEN

    PubMed Central

    Paik, Julie M.; Curhan, Gary C.; Forman, John P.; Taylor, Eric N.

    2011-01-01

    Purpose While the effects of calcium, phosphorus intake, and vitamin D on parathyroid hormone (PTH) have been well studied, less is known about other factors that impact PTH. Our goal was to delineate associations between demographic, dietary, and plasma factors and PTH. Methods We conducted a cross-sectional study of intact PTH among 1,288 non-black women in the Nurses Health Study II aged 33–53 with BMI < 30kg/m2 and eGFR ≥60 ml/min/1.73m2. Results Median PTH was 30.7pg/ml. After adjusting for 25-hydroxyvitamin D and other factors, PTH was 4.1pg/ml lower (95% CI −7.7 to −0.5) in women who smoked 1–14 cigarettes/day and 6.4pg/ml lower (95% CI −11.2 to −1.7) in women who smoked >15 cigarettes/day compared to non-smokers. After multivariate adjustment, women whose BMI was 27–29 kg/m2 had PTH levels 2.0pg/ml higher (95% CI 0.2–3.9) compared to BMI of 21–22 kg/m2, and women in the highest quartile of plasma phosphorus had PTH levels 4.1pg/ml lower (95% CI −5.8 to −2.4) than women in the lowest quartile. Higher vitamin A intake was independently associated with lower PTH whereas lower calcium intake, lower plasma calcium, lower plasma 25-hydroxyvitamin D, and winter blood draw were associated with higher PTH. Intakes of phosphorus, animal protein, magnesium, alcohol, and caffeine were not associated with PTH. Conclusions Factors not classically associated with calcium-phosphorus metabolism impact PTH. Additional research is needed to elucidate the mechanisms whereby smoking, vitamin A, and phosphorus affect PTH and to examine how body size and season may affect PTH independent of 25(OH)D. PMID:20631996

  6. Parathyroid adenoma associated with neurofibromatosis: Correlative scintigraphic and magnetic resonance imaging

    SciTech Connect

    Vogelzang, P.J.; Oates, E.; Bankoff, M.S.

    1989-03-01

    Correlative imaging by dual-isotope thallium/technetium subtraction scintigraphy, computed tomography, and magnetic resonance imaging demonstrated a pathologically proven parathyroid adenoma in a 62-year-old man with known neurofibromatosis, who presented with hypercalcemia and an elevated parathormone level. The association between neurofibromatosis and primary hyperparathyroidism is discussed.

  7. The association of adiposity with parathyroid hormone in healthy older adults

    PubMed Central

    Pitroda, Arpita Patel; Dawson-Hughes, Bess

    2010-01-01

    Elevated parathyroid hormone (PTH) is a risk factor for increased morbidity and mortality. PTH levels increase with adiposity in older adults but the basis for this association is unclear. The objective of this study was to examine the association of percent body fat (%Fat) with serum PTH in 307 older men and women and to determine the extent to which it may be explained by vitamin D status, bone turnover, calcium metabolism, and glucose homeostasis. The data are from the baseline visit of a clinical trial of calcium and vitamin D to prevent bone loss. %Fat was measured by dual-energy X-ray absorptiometry and fasting blood and urine samples were collected. Serum PTH levels increased by about 0.4 pmol/l per 10 unit increase in percent body fat (P = 0.003). The variables that we examined, including plasma 25-hydroxyvitamin D and serum osteocalcin, calcium, phosphorus, and insulin explained only a small proportion of this association (18%). Further work is needed to identify the mediators of the higher PTH levels in subjects with greater adiposity. This is important in view of worldwide increases in overweight and obesity and the potential contribution of elevated PTH to morbidity and mortality. PMID:19711204

  8. Dynein light chain binding to a 3′-untranslated sequence mediates parathyroid hormone mRNA association with microtubules

    PubMed Central

    Epstein, Eyal; Sela-Brown, Alin; Ringel, Israel; Kilav, Rachel; King, Stephen M.; Benashski, Sharon E.; Yisraeli, Joel K.; Silver, Justin; Naveh-Many, Tally

    2000-01-01

    The 3′-untranslated region (UTR) of mRNAs binds proteins that determine mRNA stability and localization. The 3′-UTR of parathyroid hormone (PTH) mRNA specifically binds cytoplasmic proteins. We screened an expression library for proteins that bind the PTH mRNA 3′-UTR, and the sequence of 1 clone was identical to that of the dynein light chain LC8, a component of the dynein complexes that translocate cytoplasmic components along microtubules. Recombinant LC8 binds PTH mRNA 3′-UTR, as shown by RNA electrophoretic mobility shift assay. We showed that PTH mRNA colocalizes with microtubules in the parathyroid gland, as well as with a purified microtubule preparation from calf brain, and that this association was mediated by LC8. To our knowledge, this is the first report of a dynein complex protein binding an mRNA. The dynein complex may be the motor that is responsible for transporting mRNAs to specific locations in the cytoplasm and for the consequent is asymmetric distribution of translated proteins in the cell. PMID:10683380

  9. Parathyroid cancer

    MedlinePlus

    ... due to parathyroid cancer: A drug called gallium nitrate, which lowers the calcium level in the blood ... Hypercalcemia Multiple endocrine neoplasia (MEN) I Parathyroid gland removal Review Date 2/11/2016 Updated by: Todd ...

  10. Thymus-Associated Parathyroid Hormone Has Two Cellular Origins with Distinct Endocrine and Immunological Functions

    PubMed Central

    Liu, Zhijie; Farley, Alison; Chen, Lizhen; Kirby, Beth J.; Kovacs, Christopher S.; Blackburn, C. Clare; Manley, Nancy R.

    2010-01-01

    In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2 −/− mutants. However, the developmental ontogeny and cellular identity of these “thymic” PTH–expressing cells is unknown. We found that the lethality of aparathyroid Gcm2 −/− mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2 −/− mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant

  11. Primary hyperparathyroidism due to an intrathyroidal parathyroid adenoma associated with chronic lymphocytic thyroiditis.

    PubMed

    Cating-Cabral, Monica Therese; Cabungcal, Arsenio Claro; Villafuerte, Cesar Vincent; Añel-Quimpo, Joselynna

    2012-06-08

    This is a case of a 44-year-old woman with an anterior neck mass and hypothyroidism who presented with an incidental finding of an elevated serum calcium level and was found to have primary hyperparathyroidism and osteoporosis. During surgical exploration no parathyroid adenoma was found, although a nodule was palpated within the right thyroid lobe. Examination of the excised right thyroid lobe revealed an intrathyroidal parathyroid adenoma and chronic lymphocytic thyroiditis. After surgery, she did not develop severe hypocalcaemia and this was attributed to preoperative treatment with pamidronate. In the months following surgery, parathyroid hormone remained undetectable.

  12. Parathyroid cancer

    PubMed Central

    McClenaghan, Fiona

    2015-01-01

    Parathyroid carcinoma is an exceedingly rare endocrine malignancy first described in 1933. It accounts for between 0.5% and 5% of all cases of primary hyperparathyroidism. Parathyroid carcinoma is unusual among endocrine malignancies, being more hormonally active than its benign counterpart. Parathyroid carcinoma poses a diagnostic challenge both clinically and histologically due to the lack of features which can definitively distinguish malignant from benign disease early in its clinical course. Here, we describe the clinical features of the disease, and present the current opinion on optimal management. Further, we analyse the most recent histological advances made to aid in the diagnosis and management of this rare, but potentially devastating, disease. PMID:26312219

  13. Parathyroid biopsy

    MedlinePlus

    ... parathyroid disorders. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck ... of Surgery, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA. Review provided by VeriMed ...

  14. Dynamic Na+-H+ exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains.

    PubMed

    Ardura, Juan A; Wang, Bin; Watkins, Simon C; Vilardaga, Jean-Pierre; Friedman, Peter A

    2011-10-07

    Na/H exchanger regulatory factor-1 (NHERF1) is a cytoplasmic PDZ (postsynaptic density 95/disc large/zona occludens) protein that assembles macromolecular complexes and determines the localization, trafficking, and signaling of select G protein-coupled receptors and other membrane-delimited proteins. The parathyroid hormone receptor (PTHR), which regulates mineral ion homeostasis and bone turnover, is a G protein-coupled receptor harboring a PDZ-binding motif that enables association with NHERF1 and tethering to the actin cytoskeleton. NHERF1 interactions with the PTHR modify its trafficking and signaling. Here, we characterized by live cell imaging the mechanism whereby NHERF1 coordinates the interactions of multiple proteins, as well as the fate of NHERF1 itself upon receptor activation. Upon PTHR stimulation, NHERF1 rapidly dissociates from the receptor and induces receptor aggregation in long lasting clusters that are enriched with the actin-binding protein ezrin and with clathrin. After NHERF1 dissociates from the PTHR, ezrin then directly interacts with the PTHR to stabilize the PTHR at the cell membrane. Recruitment of β-arrestins to the PTHR is delayed until NHERF1 dissociates from the receptor, which is then trafficked to clathrin for internalization. The ability of NHERF to interact dynamically with the PTHR and cognate adapter proteins regulates receptor trafficking and signaling in a spatially and temporally coordinated manner.

  15. Induction of tolerance to parental parathyroid grafts using allogeneic thymus tissue in patients with DiGeorge anomaly.

    PubMed

    Chinn, Ivan K; Markert, M Louise

    2011-06-01

    DiGeorge anomaly can affect both thymic and parathyroid function. Although athymia is corrected by allogeneic thymus transplantation, treatment options for hypoparathyroidism have been unsatisfactory. Parathyroid transplantation offers the potential for definitive cure but remains challenging because of graft rejection. Some allogeneic parathyroid grafts have functioned in adult recipients in the context of immunosuppression for renal transplantation. Other efforts have attempted to reduce the allogenicity of the parathyroid grafts through manipulation of the parathyroid tissues before transplantation (by using encapsulation or special culture techniques). Recently, we demonstrated the efficacy of parental parathyroid transplantation when combined with allogeneic thymus transplantation in an infant with complete DiGeorge anomaly. The recipient developed tolerance toward the parathyroid donor. The parathyroid graft has functioned for 5 years after transplantation without the need for continued immunosuppression or calcium supplementation. We observed that matching of the allogeneic thymus graft to the parathyroid donor HLA class II alleles that are unshared with the recipient appears to be associated with the induction of tolerance toward the parathyroid graft. Further work is needed to determine the optimal means for using combined allogeneic thymus and parental parathyroid transplantation to correct hypoparathyroidism in patients with both complete and partial DiGeorge anomaly.

  16. Serum vitamin D, intact parathyroid hormone, and Fetuin A concentrations were associated with geriatric sarcopenia and cardiac hypertrophy

    PubMed Central

    Chang, Wei-Ting; Wu, Chih-Hsing; Hsu, Ling-Wei; Chen, Po-Wei; Yu, Jia-Rong; Chang, Chin-Sung; Tsai, Wei-Chuan; Liu, Ping-Yen

    2017-01-01

    With aging, intact parathyroid hormone (iPTH) increases. It plays a crucial role in left ventricular hypertrophy (LVH). Also, 25-hydroxy vitamin D (Vit-D) and iPTH have been observed to be determinants of muscle wasting known as sarcopenia. Fetuin A (FetA), a systemic calcification inhibitor, involves in the development of diastolic heart failure. Hence, we hypothesized that the interplay among FetA, Vit-D and iPTH may contribute to sarcopenic LVH among the elders. We analyzed a database from the Tianliao Old People study with 541 elders (≥65 years) in a Taiwan’s suburban community. After excluding patients with renal function impairment, 120/449 (26.7%) patients were diagnosed with sarcopenia. Sarcopenic patients had lower serum Vit-D levels but higher FetA as well as iPTH. Notably, sarcopenic patients with LVH had significantly lower FetA and higher iPTH levels. In multivariate logistic regression analysis, only the increase in iPTH was independently associated with sarcopenic LVH (Odds ratio: 1.05; confidence interval: 1.03–1.08, p = 0.005). Using iPTH >52.3 ng/l as a cutoff point, the sensitivity and specificity was 66% and 84%, respectively. In conclusion, FetA, Vit-D, and iPTH levels were all associated with sarcopenia in this geriatric population. Among them, iPTH specifically indicates patients with sarcopenic LVH. PMID:28112206

  17. Urolithiasis and primary parathyroid adenoma: report of one case.

    PubMed

    Lee, Jing-Sheng; Lau, Beng-Huat; Yeh, Ming-Lun; Lee, Chin-Cheng

    2003-01-01

    A 12-year-old girl was admitted to ward because of persistent left flank pain, vomiting, and hematuria. A stone was located at the ureteropelvic junction of the left kidney, as determined by means of abdominal sonography. Metabolic investigation for a renal stone revealed that she had hypercalcemia, hypophosphatemia, and hypercalciuria. Hyperparathyroidism was diagnosed based on the hypercalcemia and inappropriately elevated serum parathyroid hormone level. A parathyroid adenoma was successfully diagnosed by using thallium/technetium subtraction parathyroid scanning. Extracorporeal shock wave lithotripsy was performed to treat the renal stone, and the parathyroid adenoma was successfully removed. The patient's postoperative course was uneventful. This case is presented because urolithiasis and hyperparathyroidism are rare in children. Metabolic evaluation is mandatory in children with a renal stone. Further investigation for the hyperparathyroidism should be performed if hypercalcemia associated with hypercalciuria is documented.

  18. Association between long-term efficacy of cinacalcet and parathyroid gland volume in haemodialysis patients with secondary hyperparathyroidism

    PubMed Central

    Tanaka, Motoko; Nakanishi, Shohei; Komaba, Hirotaka; Itoh, Kazuko; Matsushita, Kazutaka; Fukagawa, Masafumi

    2008-01-01

    Purpose. Secondary hyperparathyroidism with nodular hyperplasia is resistant to medical therapies. Cinacalcet is an effective treatment for severe secondary hyperparathyroidism. This multicentre retrospective study was designed to determine the long-term efficacy of cinacalcet in patients with nodular hyperplasia, the advanced type of parathyroid hyperplasia. Subjects and methods. The study subjects were 20 haemodialysis patients with secondary hyperparathyroidism. Patients with ultrasonographically confirmed large parathyroid glands (volume >0.5 cm3) were considered to have nodular hyperplasia (n = 8). Cinacalcet was started at the dose of 25 mg/day and titrated up to 100 mg/day to achieve the target intact-parathyroid hormone (iPTH) level of <250 pg/ml. Serum iPTH, corrected calcium, serum phosphorus, calcium × phosphorus product were measured and compared over the 48-week period of treatment with cinacalcet in all 20 patients and over 120 weeks in 6 of the patients (2 with nodular hyperplasia and 4 with non-nodular hyperplasia). We also examined the achievement rate of K/DOQI guideline treatment targets. The dosages of vitamin D preparation, sevelamer hydrochloride and calcium- containing phosphate binder were adjusted for the above target values. Results. iPTH levels were significantly lower at 48 weeks in both groups. However, corrected calcium levels, serum phosphorus levels and calcium phosphorus products were within the target values in the non-nodular hyperplasia group (n = 12), while the target value could not be achieved in the nodular hyperplasia group. In the long-term follow-up group, the levels of iPTH, corrected calcium, serum phosphorus and calcium × phosphorus products were significantly higher in nodular hyperplasia than in non-nodular hyperplasia. Conclusion. Our study suggests that cinacalcet lacks long-term efficacy in nodular hyperplasia, especially for controlling serum calcium and phosphorus levels. PMID:25983974

  19. Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients

    PubMed Central

    Jeong, Sohyun; Oh, Jung Mi

    2017-01-01

    Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (<150 pg/mL) and 41 patients had high iPTH (≥150 pg/mL). Total RNA was extracted from whole blood samples. Total RNA from 15 patients (7 and 8 patients in the low and high iPTH groups, respectively) underwent miRNA microarray analysis, and three differentially upregulated (>2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development. PMID:28152049

  20. Richter's Syndrome with Hypercalcemia Induced by Tumor-Associated Production of Parathyroid Hormone-Related Peptide

    PubMed Central

    Watanabe, Naoki; Yasuda, Hajime; Morishita, Soji; Aota, Yasuo; Tomomatsu, Junichi; Tanaka, Masaru; Ohsaka, Akimichi; Komatsu, Norio

    2017-01-01

    Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method. The presented case did not have hypercalcemia when initially diagnosed as small lymphocytic lymphoma (SLL), and as reported earlier, the development of hypercalcemia may be an indication of the transformation to Richter's syndrome in patients with CLL/SLL. PMID:28203174

  1. Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans.

    PubMed

    Cañadillas, Sagrario; Canalejo, Antonio; Santamaría, Rafael; Rodríguez, Maria E; Estepa, Jose C; Martín-Malo, Alejandro; Bravo, Juan; Ramos, Blanca; Aguilera-Tejero, Escolastico; Rodríguez, Mariano; Almadén, Yolanda

    2005-07-01

    In uremic patients, severe parathyroid hyperplasia is associated with reduced parathyroid calcium-sensing receptor (CaR) expression. Thus, in these patients, a high serum Ca concentration may be required to inhibit parathyroid hormone (PTH) secretion. This study compares the magnitude of reduction in CaR expression and the degree of the abnormality in Ca-regulated PTH release in vitro. A total of 50 glands from 23 hemodialysis patients with refractory hyperparathyroidism were studied. Tissue slices were incubated in vitro to evaluate (1) the PTH secretory output in a normal Ca concentration (1.25 mM) and (2) the PTH secretory response to high (1.5 mM) and low (0.6 mM) Ca concentration. Tissue aliquots were processed for determination of CaRmRNA expression. The results showed that, corrected for DNA, parathyroid tissue with lowest CaR expression secreted more PTH than that with relatively high CaR expression (146 +/- 23 versus 60 +/- 2 pg/microg DNA; P < 0.01). Furthermore, glands with low CaR expression demonstrated a blunted PTH secretory response to both the inhibitory effect of high Ca and the stimulatory effect of low Ca. The study also showed that the larger the gland, the lower the CaRmRNA expression. Thus, large parathyroid glands produce a large amount of PTH not only as a result of the increased gland size but also because the parathyroid tissue secretory output is increased. These abnormalities in PTH regulation are related to low CaR expression.

  2. The anatomic basis of parathyroid surgery.

    PubMed

    Wang, C

    1976-03-01

    A study of 645 normal adult parathyroid glands in 160 cadavers revealed that there is a definite pattern of anatomic distribution on the basis of the embryologic development of the parathyroid, thyroid, and thymic glands. The sites of predilection of the upper gland (Parathyroid IV) are, in order of frequency, the cricothyroid junction; the dorsum of the upper pole of the thyroid; and the retropharyngeal space. Those of the lower gland (Parathyroid III) are at the lower pole of the thyroid and the thymic tongue; rarely in the upper, the lateral neck, or the mediastinum. An understanding of the developmental relationship of the parathyroid glands to the thyroid and the thymus is fundamental in the delineation of the embryologic origin of the parathyroid glands. The parathyroid gland, located within the surgical capsule of the thyroid (subcapsular), when diseased, remains in place locally. A gland outside of the capsule (extracapsular) is often displaced into the posterior or anterior mediastinum. A collective assessment of the size, weight, color, shape, and consistency of the parathyroid gland is mandatory in the determination of its normalcy. Frozen section examination for stromal and intracellular fatty content is an added assurance of normalcy. That parathyroid glands sink in saline solution, and fat globules float, may aid in differentiating the two types of tissue. Supernumerary, fused, and intrathyroidal parathyroids, albeit rare, are of surgical importance.

  3. Does Levothyroxine Administration Impact Parathyroid Localization?

    PubMed Central

    Ayers, Rachell R.; Tobin, Kirby; Sippel, Rebecca S.; Balentine, Courtney; Elfenbein, Dawn; Chen, Herbert; Schneider, David F.

    2016-01-01

    Background Proper localization is crucial in performing minimally invasive parathyroidectomy for primary hyperparathyroidism (PHPT). Ultrasonography (US) and Tc-99m sestamibi (MIBI) scintigraphy are common methods used for localization. As the appearance and activity of the thyroid gland may impact parathyroid localization, the purpose of this study was to determine how exogenous use of the thyroid hormone, levothyroxine (LT), affects parathyroid localization. Methods Adult patients with non-familial PHPT who underwent initial parathyroidectomy from 2000 to 2014 were retrospectively identified. Levothyroxine (+LT) and non-levothyroxine (-LT) patients were matched 1:3 based on age, gender, goiter status, and preoperative parathyroid hormone levels. Subgroup analysis was performed on patients previously treated with radioactive iodine and patients undergoing single adenoma resection. Results Of the 1,737 patients that met inclusion criteria, 286 were on LT at the time of their parathyroid localization scan. Use of LT not did impact the percentage of correct MIBI localization scans when compared to −LT patients (p=0.83). Interestingly, use of LT significantly hindered localization by US in comparison to the −LT group (48.4 vs 62.2%, p<0.01). When examining only patients where a single upper gland was removed, the +LT group was less likely to have a correct US compared to the −LT group (50 vs. 72.8%, p<0.01). However, there was no difference in US accuracy for patients who only had a single lower gland removed (p=0.51). Conclusions Exogenous levothyroxine is associated with impaired parathyroid localization with US but not MIBI. Surgeons should be aware of localization efficiency for this subset of patients in the era of personalized medicine and cost effectiveness. PMID:25917998

  4. Parathyroid hormone - Secretion and metabolism in vivo.

    NASA Technical Reports Server (NTRS)

    Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

    1971-01-01

    Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

  5. Receptors for parathyroid hormone and parathyroid hormone-related peptide: from molecular cloning to definition of diseases.

    PubMed

    Jüppner, H; Schipani, E

    1996-07-01

    The parathyroid hormone/parathyroid hormone-related peptide receptor belongs to a distinct family of G protein-coupled receptors, the members of which usually signal through at least two second messenger systems, adenylate cyclase and phospholipase C. The parathyroid hormone/ parathyroid hormone-related peptide receptor is most abundantly expressed in bone, kidney and growth-plate chondrocytes, and, at lower levels, in a variety of fetal and adult tissues. To search for human diseases that are caused by parathyroid hormone/parathyroid hormone-related peptide receptor defects, genomic DNA of patients with pseudohypoparathyroidism type Ib and of patients with Jansen's metaphyseal chondrodysplasia was screened for mutations in all coding exons of the receptor gene. Inactivating parathyroid hormone/parathyroid hormone-related peptide receptor mutations were excluded in patients with pseudohypoparathyroidism type Ib. However, a receptor mutation that causes agonist-independent, constitutive cAMP accumulation was identified in a patient with Jansen's metaphyseal chondrodysplasia, a rare form of short-limbed dwarfism associated with hypercalcemia despite normal or low concentrations of parathyroid hormone and parathyroid hormone-related peptide. These findings allow the conclusion to be drawn that parathyroid hormone/parathyroid hormone-related peptide receptors mediate the endocrine actions of parathyroid hormone, which are required for the control of calcium homeostasis and the autocrine-paracrine actions of parathyroid hormone-related peptide, which are required for normal growth-plate development.

  6. Minimally invasive parathyroid surgery

    PubMed Central

    Noureldine, Salem I.; Gooi, Zhen

    2015-01-01

    Traditionally, bilateral cervical exploration for localization of all four parathyroid glands and removal of any that are grossly enlarged has been the standard surgical treatment for primary hyperparathyroidism (PHPT). With the advances in preoperative localization studies and greater public demand for less invasive procedures, novel targeted, minimally invasive techniques to the parathyroid glands have been described and practiced over the past 2 decades. Minimally invasive parathyroidectomy (MIP) can be done either through the standard Kocher incision, a smaller midline incision, with video assistance (purely endoscopic and video-assisted techniques), or through an ectopically placed, extracervical, incision. In current practice, once PHPT is diagnosed, preoperative evaluation using high-resolution radiographic imaging to localize the offending parathyroid gland is essential if MIP is to be considered. The imaging study results suggest where the surgeon should begin the focused procedure and serve as a road map to allow tailoring of an efficient, imaging-guided dissection while eliminating the unnecessary dissection of multiple glands or a bilateral exploration. Intraoperative parathyroid hormone (IOPTH) levels may be measured during the procedure, or a gamma probe used during radioguided parathyroidectomy, to ascertain that the correct gland has been excised and that no other hyperfunctional tissue is present. MIP has many advantages over the traditional bilateral, four-gland exploration. MIP can be performed using local anesthesia, requires less operative time, results in fewer complications, and offers an improved cosmetic result and greater patient satisfaction. Additional advantages of MIP are earlier hospital discharge and decreased overall associated costs. This article aims to address the considerations for accomplishing MIP, including the role of preoperative imaging studies, intraoperative adjuncts, and surgical techniques. PMID:26425454

  7. Nonfunctioning parathyroid carcinoma

    SciTech Connect

    Klink, B.K.; Karulf, R.E.; Maimon, W.N.; Peoples, J.B. )

    1991-07-01

    Parathyroid carcinoma is a rare clinical entity accounting for only 4 per cent of all cases of parathyroid neoplasia. Nonfunctioning parathyroid carcinoma is even rarer. Previously, virtually all patients with these lesions were treated for a nonspecific neck mass. However, in the present case, a preoperative diagnosis of nonfunctioning parathyroid carcinoma was made based on the technetium pertechnetate/thallium 201 subtraction scan. The authors report on the 14th case of nonfunctioning parathyroid carcinoma, a review of the literature, and guidelines for the preoperative and operative evaluation of neck masses suspected to be parathyroid carcinoma.22 references.

  8. Parathyroids and ultimobranchial bodies in monotremes.

    PubMed

    Haynes, J I

    1999-02-01

    Only scant information is available in the scientific literature on the parathyroids and ultimobranchial bodies in the primitive mammals, the echidna (Tachyglossus aculeatus) and platypus (Ornithorhynchus anatinus). The major aim of this paper is to describe the morphology of the monotreme parathyroid gland and to compare it with parathyroids in mammals and reptiles. The gross anatomy and light microscopic structure of the ultimobranchial body, thymus, and thyroid are also given. Animals were dissected and routine light and electron microscopic techniques used to examine the microscopic morphology. The locations of parathyroid hormone, calcitonin and calcitonin gene-related peptide in tissue sections were identified by immunostaining. Monotremes have one pair of parathyroid glands located in the thorax and they are often associated with thymic tissue but never with the thyroid which is also present in the mediastinum. Ultimobranchial bodies are ventrolateral to the commencement of the trachea. Thymic lobules with Hassall's corpuscles are scattered in the fibrofatty tissue of the mediastinum and the ventral surface of the pericardium. Histologically, principal cells, water-clear cells, and non-secretory cells were identified in the parathyroid glands. Principal cells showed polarity and had microlamellar projections that formed intercellular canaliculi. Non-secretory cells had features similar to those of thymic epithelial reticular cells. Immunostaining of parathyroid hormone showed a diffuse distribution in parathyroid principal cells and none in ultimobranchial bodies. Identification of the ultimobranchial bodies was confirmed by immunostaining. The monotreme parathyroid gland, ultimobranchial bodies and thyroid show reptilian as well as mammalian features.

  9. Association of 25-hydroxyvitamin D and parathyroid hormone with the metabolic syndrome in black South African women.

    PubMed

    Sotunde, Olusola Funmilayo; Kruger, Herculina Salome; Wright, Hattie H; Havemann-Nel, Lize; Mels, Carina M C; Ravyse, Chrisna; Pieters, Marlien

    2017-04-01

    The relationship between 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and metabolic traits appear to differ among ethnicities and may be influenced by obesity. The aim of the study was to examine the association of serum 25(OH)D or PTH with metabolic syndrome (MetS) while controlling for adiposity in black women. Using a cross-sectional study design, 209 urban black women aged ≥ 43 years from the North West Province, South Africa, were included. Multiple regression models were used to explore the relationship between 25(OH)D or PTH and body composition. To explore the association between 25(OH)D or PTH and MetS, a separate variable was created including at least 3 of the MetS criteria, but excluding elevated waist circumference as a diagnostic criterion in a logistic regression model. The majority of the women (69.9%) were overweight or obese and 65.5% of the women had excessive adiposity using the age-specific cut-off points for body fat percentage. All body composition variables were positively associated with PTH, whereas body mass index and waist circumference, but not body fat percentage, had negative associations with 25(OH)D also after adjusting for confounders. Before and after adjusting for age, body fat, habitual physical activity, tobacco use, season of data collection, and estimated glomerular filtration rate, neither 25(OH)D nor PTH showed significant associations with MetS. Although PTH was positively associated and 25(OH)D was negatively associated with adiposity in black women, there was no association between either 25(OH)D or PTH and MetS in this study population, nor did adiposity influence these relationships.

  10. Association of Relatively Low Serum Parathyroid Hormone with Malnutrition-Inflammation Complex and Survival in Maintenance Hemodialysis Patients

    PubMed Central

    Dukkipati, Ramanath; Kovesdy, Csaba P.; Kim, Youngmee; Colman, Sara; Budoff, Matthew J; Nissenson, Allen R.; Sprague, Stuart M.; Kopple, Joel D; Kalantar-Zadeh, Kamyar

    2011-01-01

    Background Low serum parathyroid hormone (PTH) has been implicated as a primary biochemical marker of adynamic bone disease in individuals with chronic kidney disease (CKD) who undergo maintenance hemodialysis (MHD) treatment. We hypothesized that the malnutrition-inflammation complex is associated with low PTH levels in these patients and confounds the PTH-survival association. Methods We examined 748 stable MHD outpatients in Southern California and followed them for up to 5 years (10/2001-12/2006). Results In 748 MHD patients, serum PTH <150 pg/ml was more prevalent among non-Blacks and diabetics. There was no association between serum PTH and coronary artery calcification score, bone mineral density or dietary protein or calorie intake. Low serum PTH was associated with markers of protein-energy wasting and inflammation, and this association confounded the relationship between serum PTH and alkaline phosphatase. Although 5-year crude mortality rates were similar across PTH increments, after adjustment for the case-mix and surrogates of malnutrition and inflammation, a moderately low serum PTH in 100 to 150 pg/ml range was associated with the greatest survival compared to other serum PTH levels, i.e., a death hazard ratio of 0.52 (95% confidence interval: 0.29-0.92, p<0.001) compared to PTH of 300 to 600 pg/ml (reference). Conclusions Low serum PTH may be another facet of the malnutrition-inflammation complex in CKD, and after controlling for this confounder, a moderately low PTH in 100 to 150 pg/ml range appears associated with the greatest survival. Limitations of observational studies should be considered. PMID:20199875

  11. A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement

    PubMed Central

    2012-01-01

    Background Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. Case presentation We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. Conclusion This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia. PMID:22840059

  12. Parathyroid glands (image)

    MedlinePlus

    The 4 parathyroid glands are located near or attached to the back side of the thyroid gland and produce pararthyroid hormone (PTH). Parathyroid hormone regulates calcium, phosphorus, and magnesium balance within ...

  13. Association between Parathyroid Hormone, 25 (OH) Vitamin D, and Chronic Kidney Disease: A Population-Based Study

    PubMed Central

    Wang, Wei-Hao; Chen, Li-Wei; Sun, Chiao-Yin; Hsu, Heng-Rong; Chien, Rong-Nang

    2017-01-01

    Identification of the accurate risk factor for CKD remains mandatory to combat the high prevalence of diseases. Growing evidence suggests the association of serum vitamin D with diverse health conditions. However, the relationship between vitamin D, intact parathyroid hormone (PTH), and calcium-phosphate metabolism and development of CKD remains controversial. We conduct this cross-sectional observational study to investigate the association between serum 25 (OH) vitamin D, intact PTH, and calcium and phosphate levels with eGFR and albuminuria, as a surrogate marker of CKD, in a community population. A total of 4080 participants were recruited. The mean age was 58.4 ± 13.3 years and 1480 (36.3%) were men. The mean eGFR was 94.1 ± 26.3 mL/min/1.73 m2. The prevalence of CKD was 19.8%. Serum 25 (OH) vitamin D and log intact PTH levels were inversely correlated with eGFR but positively correlated with log albuminuria. Logistic regression analysis identified the log intact PTH as an independent factor associated with eGFR ≤ 60 mL/min/1.73 m2 and proteinuria. This association was consistent when serum intact PTH was analyzed as continuous as well as categorical variables (as hyperparathyroidism). The relationship remains significant using resampling subset analysis with comparable baseline characteristics and adjustment for 25 (OH) vitamin D, calcium, and phosphate levels. This finding warranted further research to clarify the causal relationship of PTH/25 (OH) vitamin D with the risk of CKD in the general population. PMID:28367447

  14. Pregnancy-associated plasma protein-A modulates the anabolic effects of parathyroid hormone in mouse bone.

    PubMed

    Clifton, Kari B; Conover, Cheryl A

    2015-12-01

    Intermittent parathyroid hormone (PTH) is a potent anabolic therapy for bone, and several studies have implicated local insulin-like growth factor (IGF) signaling in mediating this effect. The IGF system is complex and includes ligands and receptors, as well as IGF binding proteins (IGFBPs) and IGFBP proteases. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease expressed by osteoblasts in vitro that has been shown to enhance local IGF action through cleavage of inhibitory IGFBP-4. This study was set up to test two specific hypotheses: 1) Intermittent PTH treatment increases the expression of IGF-I, IGFBP-4 and PAPP-A in bone in vivo, thereby increasing local IGF activity. 2) In the absence of PAPP-A, local IGF activity and the anabolic effects of PTH on bone are reduced. Wild-type (WT) and PAPP-A knock-out (KO) mice were treated with 80 μg/kg human PTH 1-34 or vehicle by subcutaneous injection five days per week for six weeks. IGF-I, IGFBP-4 and PAPP-A mRNA expression in bone were significantly increased in response to PTH treatment. PTH treatment of WT mice, but not PAPP-A KO mice, significantly increased expression of an IGF-responsive gene. Bone mineral density (BMD), as measured by DEXA, was significantly decreased in femurs of PAPP-A KO compared to WT mice with PTH treatment. Volumetric BMD, as measured by pQCT, was significantly decreased in femoral midshaft (primarily cortical bone), but not metaphysis (primarily trabecular bone), of PAPP-A KO compared to WT mice with PTH treatment. These data suggest that stimulation of PAPP-A expression by intermittent PTH treatment contributes to PTH bone anabolism in mice.

  15. Tuberous sclerosis and parathyroid adenoma.

    PubMed Central

    Mortensen, L S; Rungby, J

    1991-01-01

    Very little is known about the pathogenesis of tuberous sclerosis. Over the past 10 years, however, increasing numbers of reports on adenomatous diseases in association with tuberous sclerosis have been published. A case of hypercalcaemia and parathyroid adenoma in association with tuberous sclerosis is presented, of which there has been one such report published previously. This association might be another manifestation of this complex disease: it is therefore recommended that plasma calcium concentrations should be measured in such patients. PMID:1752991

  16. Parathyroid incidentalomas detected during thyroid ultrasonography and effect of chronic thyroiditis on false positive parathyroid lesions.

    PubMed

    Ozdemir, Didem; Arpaci, Dilek; Ucler, Rifki; Cuhaci, Neslihan; Ersoy, Reyhan; Cakir, Bekir

    2012-12-01

    We aimed to determine the prevalence of parathyroid incidentalomas in patients referred for thyroid ultrasonography (US) and investigate the role of chronic thyroiditis on false positive lesions. Patients suspected to have parathyroid lesions during thyroid US were recorded prospectively between August 2009 and January 2010. Patients referred for parathyroid US and patients with known high serum calcium or parathyroid hormone (PTH) levels were excluded. Suspected parathyroid lesions were defined as hypoechoic, homogeneous, solid lesions with regular margins located outside the thyroid lobe, most commonly inferior to the thyroid gland. Thyroid US was performed in 6,528 patients. There were 78 patients (1.19 %) (73 female and 5 male) with suspected parathyroid lesion. The diagnosis of a true parathyroid adenoma was confirmed in 6 (7.69 %) patients. In patients with true adenoma, mean serum calcium, phosphorus, and PTH levels were 10.57 ± 0.48 mg/dl, 3.03 ± 0.52 mg/dl, and 182.91 ± 46.62 pg/ml, respectively. Among 72 patients with false positive parathyroid lesion, antithyroid peroxidase antibody was positive in 50 (69.4 %), antithyroglobulin antibody was positive in 46 (63.9 %), and one of these antibodies were positive in 59 (81.9 %) patients. Also, 46 (63.9 %) of these patients had thyroid dysfunctions (43 hypothyroidism and 3 hyperthyroidism) and 59 (81.9 %) had chronic thyroiditis ultrasonographically. Parathyroid incidentaloma was detected in 0.09 % of patients referred for thyroid US. The presence of clinically or ultrasonographically chronic thyroiditis might cause inadvertent interpretation of a hypoechoic lesion as a parathyroid pathology during thyroid US.

  17. Contact endoscopy for identifying the parathyroid glands during thyroidectomy.

    PubMed

    Guimarães, A V; Brandão, L G; Dedivitis, R A

    2010-02-01

    Aim of this study was to analyse contact endoscopy as an auxiliary method for identifying parathyroid glands during thyroid surgery and to identify other variables that may interfere with this correlation. Overall, 125 patients underwent thyroid surgery between January 2004 and February 2006. The variables analysed were: the total duration of surgery; time taken to locate and identify parathyroid glands; improvement in identifying these; numbers of parathyroid glands located by the surgeon and confirmed by contact endoscopy; histopathological diagnosis; presence of thyroiditis; thyroid weight; number of parathyroid glands left in thyroid specimens; and number of parathyroid gland autotransplantations. A total of 331 parathyroid glands were observed by the surgeon. However, 282 glands were identified by contact endoscopy. Nine parathyroid glands (7.2%) were observed together with thyroid specimens (Kappa = 0.534). The longer the total duration of surgery (p = 0.03) and time taken to locate and identify (p = 0.00) the parathyroid glands by contact endoscopy, the lower the observed agreement. The second year of performing contact endoscopy led to better agreement between the results (p = 0.02). In conclusion, contact endoscopy is an efficient auxiliary method for identifying parathyroid glands during thyroid surgery. During the period studied, association between total duration of surgery and time taken to locate and identify parathyroid glands was statistically significant.

  18. [Pathology of parathyroid glands: Practical aspects for routine pathological investigations].

    PubMed

    Sheu-Grabellus, S-Y; Schmid, K W

    2015-05-01

    The diagnostic histopathology of parathyroid glands comprises mostly benign diseases associated with primary, secondary and rarely tertiary hyperparathyroidism. Parathyroid adenoma and hyperplasia are the most common diagnoses, whereas parathyroid carcinomas and atypical adenomas are exceptional causes of hyperparathyroidism, the latter being purely a diagnosis by exclusion. This article deals with the major histopathological criteria of the various diagnoses with special emphasis on the clinical manifestation.

  19. Antibodies to parathyroid hormone-related protein lower serum calcium in athymic mouse models of malignancy-associated hypercalcemia due to human tumors.

    PubMed Central

    Kukreja, S C; Shevrin, D H; Wimbiscus, S A; Ebeling, P R; Danks, J A; Rodda, C P; Wood, W I; Martin, T J

    1988-01-01

    A parathyroid hormone-related protein (PTHrP) has recently been isolated from tumors associated with hypercalcemia. In the present study, we tested the effects of neutralizing antisera to the PTHrP on serum calcium and urine cAMP in two animal models of malignancy-associated hypercalcemia. The animal models consisted of (a) a human squamous cell lung cancer and (b) a human laryngeal cancer, both serially carried in athymic mice. The antisera specifically reduced the elevated serum calcium and urinary cAMP levels in the tumor-bearing animals. We conclude that PTHrP plays a major role in the pathogenesis of malignancy-associated hypercalcemia. PMID:2846659

  20. Parathyroid Hormone Levels and Cognition

    NASA Technical Reports Server (NTRS)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  1. About the Parathyroid Glands

    MedlinePlus

    ... the kidneys, increasing your chances of having a kidney stone. In fact, everyone with a fracture that isn’ ... of major trauma and everyone who has a kidney stone should have blood calcium and parathyroid hormone measured. ...

  2. Aluminum, parathyroid hormone, and osteomalacia

    SciTech Connect

    Burnatowska-Hledin, M.A.; Kaiser, L.; Mayor, G.H.

    1983-01-01

    Aluminum exposure in man is unavoidable. The occurrence of dialysis dementia, vitamin D-resistant osteomalacia, and hypochromic microcytic anemia in dialysis patients underscores the potential for aluminum toxicity. Although exposure via dialysate and hyperalimentation leads to significant tissue aluminum accumulation, the ubiquitous occurrence of aluminum and the severe pathology associated with large aluminum burdens suggest that smaller exposures via the gastrointestinal tract and lungs could represent an important, though largely unrecognized, public health problem. It is clear that some aluminum absorption occurs with the ingestion of small amounts of aluminum in the diet and medicines, and even greater aluminum absorption is seen in individuals consuming large amounts of aluminum present in antacids. Aluminum absorption is enhanced in the presence of elevated circulating parathyroid hormone. In addition, elevated PTH leads to the preferential deposition of aluminum in brain and bone. Consequently, PTH is likely to be involved in the pathogenesis of toxicities in those organs. PTH excess also seems to lead to the deposition of aluminum in the parathyroid gland. The in vitro demonstration that aluminum inhibits parathyroid hormone release is consistent with the findings of a euparathyroid state in dialysis patients with aluminum related vitamin D-resistant osteomalacia. Nevertheless, it seems likely that hyperparathyroidism is at least initially involved in the pathogenesis of aluminum neurotoxicity and osteomalacia; the increases in tissue aluminum stores are followed by suppression of parathyroid hormone release, which is required for the evolution of osteomalacia. Impaired renal function is not a prerequisite for increased tissue aluminum burdens, nor for aluminum-related organ toxicity. Consequently, it is likely that these diseases will be observed in populations other than those with chronic renal disease.

  3. Ectopic parathyroid glands and their anatomical, clinical and surgical implications.

    PubMed

    Noussios, G; Anagnostis, P; Natsis, K

    2012-11-01

    Ectopic parathyroid glands result from aberrant migration during early stages of development and lack of successful identification may lead to lack of success in parathyroid surgery. They constitute a common etiology of persistent or recurrent hyperparathyroidism, when they are missed at initial diagnosis. Their prevalence is about 2-43% in anatomical series and up to 16% and 14% in patients with primary and secondary hyperparathyroidism, respectively. Ectopic inferior parathyroids are most frequently found in the anterior mediastinum, in association with the thymus or the thyroid gland, while the most common position for ectopic superior parathyroids is the tracheoesophageal groove and retroesophageal region. Neck ultrasound and 99mTc Sestamibi scan are first-line imaging modalities, although with low sensitivity and specificity. However, their combination with modern techniques, such as single photon emission computed tomography (SPECT) alone or in combination with CT (SPECT/CT) increases their diagnostic accuracy. Fine needle-aspiration cytology of a lesion suspicious for parathyroid tissue and measurement of parathyroid hormone (PTH) in the aspired material further assist to the successful preoperative localization of ectopic glands. Common sites for surgical investigation are the upper thyroid pole and the upper vascular thyroid stalk behind the hypopharynx and cervical esophagus for the superior parathyroids, and the carotid artery bifurcation and the thymic tongue, for the inferior parathyroids. Radioguided minimally invasive parathyroidectomy after successful localization, assisted by rapid PTH measurement postoperatively, significantly improves surgical outcomes in patients with ectopic parathyroid adenomas.

  4. Coexisiting adenoma and granuloma involving the right inferior parathyroid gland with adjacent ectopic thymic tissue

    PubMed Central

    Gupta, Mayank; Kandasamy, Subramaniam

    2014-01-01

    Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. PMID:24957592

  5. Undescended parathyroid adenoma

    PubMed Central

    Maawy, Ali A; Oh, Deborah K; Bouvet, Michael

    2015-01-01

    Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels. PMID:25737222

  6. [Inflammation of the parathyroid glands].

    PubMed

    Ting, S; Synoracki, S; Sheu, S-Y; Schmid, K W

    2016-05-01

    Inflammation of the parathyroid glands is rare when compared to other endocrine organs. This leads to the use of descriptive terms as well as the lack of a generally accepted classification for inflammatory disorders of the parathyroid glands. This review article proposes that parathyroid inflammation be subdivided morphologically into (a) non-specific lymphocytic infiltration, which is more an expression of damage to small vessels, due to e. g. severe systemic inflammation or myocardial infarction, (b) autoimmunogenic lymphocytic parathyroiditis, (c) nonimmunogenic inflammation caused by granulomatous diseases or infections and (d) invasive sclerosing (peri) parathyroiditis. As only parathyroid glands removed due to hyperparathyroidism and normal parathyroid glands incidentally removed during thyroid surgery are seen almost exclusively in routine histopathology, virtually no information about the morphological correlate of hypoparathyroidism is available.

  7. Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD

    PubMed Central

    Miller, Gerald; Davis, James; Shatzen, Edward; Colloton, Matthew; Martin, David

    2012-01-01

    Background. Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar®/Mimpara®); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT. Methods. We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT. Results. Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet-mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium. Conclusions. The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH. PMID:22036941

  8. Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy

    SciTech Connect

    Mangin, M.; Webb, A.C.; Dreyer, B.E.; Posillico, J.T.; Ikeda, K.; Weir, E.C.; Stewart, A.F.; Bander, N.H.; Milstone, L.; Barton, D.E.

    1988-01-01

    Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome that appears to be mediated in many instances by a parathyroid hormone-like peptide. Poly(A)/sup +/ RNA from a human renal carcinoma associated with this syndrome was enriched by preparative electrophoresis and used to construct an enriched cDNA library in phage lambdagt10. The library was screened with a codon-preference oligonucleotide synthesized on the basis of a partial N-terminal amino acid sequence from a human tumor-derived peptide, and a 2.0 kilo-base cDNA was identified. The cDNA encodes a 177 amino acid protein consisting of a 36 amino acid leader sequence and a 141 amino acid mature peptide. The first 13 amino acids of the deduced sequence of the mature peptide display strong homology to human PTH, with complete divergence thereafter. RNA blot-hybridization analysis revealed multiple transcripts in mRNA from tumors associated with the humor syndrome and also in mRNA from normal human keratinocytes. Southern blot analysis of genomic DNA from humans and rodents revealed a simple pattern compatible with a single-copy gene. The gene has been mapped to chromosome 12.

  9. ON THE RELATION OF TETANY TO THE PARATHYROID GLANDS AND TO CALCIUM METABOLISM

    PubMed Central

    MacCallum, W. G.; Voegtlin, Carl

    1909-01-01

    1. Tetany occurs spontaneously in many forms and may also be produced by the destruction of the parathyroid glands. Recent researches tend to demonstrate an intimate relation between the various forms of tetany and relative or absolute insufficiency of the parathyroid gland. 2. The parathyroid glands are independent organs with definite specific function. Whether or not this function is intimately related to that of other organs of internal secretion is not as yet proven. 3. The number and distribution of the parathyroid glands varies. Failure to produce tetany experimentally is probably due to the fact that some parathyroid tissue remains after an apparently complete extirpation. When extirpation is complete tetany appears, even in herbivora. Only a very small amount of parathyroid tissue is required to prevent this. 4. The effect of the extirpation of the parathyroid glands may be annulled by the reintroduction of an extract of these glands even from an animal of widely different character. The active principle is associated with a nucleo-proteid in the extract and may be separated with this nucleo-proteid from the remaining inert albuminous substances. Its effect in counteracting tetany appears some hours after injection and lasts several days. 5. The parathyroid glands contain no considerable amount of iodine. The parathyroid extract is not an iodine containing compound. 6. In tetany there is apparently some disturbance of the composition of the circulating fluids ordinarily prevented by the secretion of the parathyroid, which disarranges the balance of the mineral constituents of the tissues. Possibly this consists in the appearance of an injurious substance of an acid nature for such tetany may he relieved by extensive bleeding with replacement of the blood by salt solution. No actual poisonous material has, however, been demonstrated by the transference of the blood of a tetanic animal to the veins of a normal one. 7. Numerous researches have shown the

  10. Prospective associations of vitamin D status with β-cell function, insulin sensitivity, and glycemia: the impact of parathyroid hormone status.

    PubMed

    Kramer, Caroline K; Swaminathan, Balakumar; Hanley, Anthony J; Connelly, Philip W; Sermer, Mathew; Zinman, Bernard; Retnakaran, Ravi

    2014-11-01

    Previous studies have yielded conflicting findings on the relationship between low vitamin D (25-OH-D) and impaired glucose homeostasis. In this context, we hypothesized that combined assessment of 25-OH-D with its regulator parathyroid hormone (PTH) may be required for optimal evaluation of the impact of vitamin D status on glucose metabolism. Thus, we evaluated the prospective associations of 25-OH-D and PTH at 3 months postpartum with β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]), insulin sensitivity (Matsuda index), and glycemia at 12 months postpartum in 494 women undergoing serial metabolic characterization. Notably, 32% of those with prediabetes/diabetes mellitus at 12 months postpartum had both vitamin D deficiency and PTH in the highest tertile at 3 months postpartum. On multiple-adjusted linear regression analyses, vitamin D deficiency/insufficiency with PTH in the highest tertile at 3 months independently predicted poorer β-cell function (P = 0.03) and insulin sensitivity (P = 0.01) and increased fasting (P = 0.03) and 2-h glucose (P = 0.002) at 12 months postpartum. In contrast, vitamin D deficiency/insufficiency with lower PTH did not predict these outcomes. In conclusion, only vitamin D deficiency/insufficiency with increased PTH is an independent predictor of β-cell dysfunction, insulin resistance, and glycemia, highlighting the need for consideration of the PTH/25-OH-D axis when studying the impact of vitamin D status on glucose homeostasis.

  11. Role of parathyroid hormone-related protein in the pro-inflammatory and pro-fibrogenic response associated with acute pancreatitis.

    PubMed

    Bhatia, Vandanajay; Kim, Sung O K; Aronson, Judith F; Chao, Celia; Hellmich, Mark R; Falzon, Miriam

    2012-04-10

    Pancreatitis is a common and potentially lethal necro-inflammatory disease with both acute and chronic manifestations. Current evidence suggests that the accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic disease, which is associated with an increased risk of pancreatic cancer. While parathyroid hormone-related protein (PTHrP) exerts multiple effects in normal physiology and disease states, its function in pancreatitis has not been previously addressed. Here we show that PTHrP levels are transiently elevated in a mouse model of cerulein-induced AP. Treatment with alcohol, a risk factor for both AP and chronic pancreatitis (CP), also increases PTHrP levels. These effects of cerulein and ethanol are evident in isolated primary acinar and stellate cells, as well as in the immortalized acinar and stellate cell lines AR42J and irPSCc3, respectively. Ethanol sensitizes acinar and stellate cells to the PTHrP-modulating effects of cerulein. Treatment of acinar cells with PTHrP (1-36) increases expression of the inflammatory mediators interleukin-6 (IL-6) and intracellular adhesion protein (ICAM-1), suggesting a potential autocrine loop. PTHrP also increases apoptosis in AR42J cells. Stellate cells mediate the fibrogenic response associated with pancreatitis; PTHrP (1-36) increases procollagen I and fibronectin mRNA levels in both primary and immortalized stellate cells. The effects of cerulein and ethanol on levels of IL-6 and procollagen I are suppressed by the PTH1R antagonist, PTHrP (7-34). Together these studies identify PTHrP as a potential mediator of the inflammatory and fibrogenic responses associated with alcoholic pancreatitis.

  12. The history of parathyroid endocrinology

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Sahay, Rakesh; Sawhney, Kanishka

    2013-01-01

    The parathyroid glands are now recognized as being essential for life. Their structure and function is well delineated, and their disease and dysfunction, well characterized. Diagnosis and management of parathyroid disease has improved in the past few decades. The path of parathyroid science, however, has been far from smooth. This paper describes the early history of parathyroid endocrinology. In doing so, it focuses on major events and discoveries, which improved the understanding and practice of our specialty. Contribution in anatomy, physiology, pathology, medicine, surgery and biochemistry are reviewed. PMID:23776911

  13. Diffuse PTH expression in parathyroid tumors argues against important functional tumor subclones

    PubMed Central

    Juhlin, C Christofer; Kiss, Nimrod B; Larsson, Catharina; Nilsson, Inga-Lena; Höög, Anders

    2016-01-01

    Abstract Objective Primary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium–PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as the regulatory factors including phosphate, vitamin D, and fibroblast growth factor 23. Design A total of 154 parathyroid tumors were analyzed by PTH immunohistochemistry and chromogenic in situ hybridization of PTH mRNA. A subset of samples (n = 34) was analyzed using quantitative real-time PCR. Results Low tumor PTH mRNA level was significantly associated with low tumor PTH immunoreactivity (P = 0.026), but the two did not correlate with regard to histological distribution within individual tumors. Tumors displaying reduced PTH mRNA levels as compared with normal rim were significantly larger (P = 0.013) and showed higher expression of the calcium-sensing receptor (CASR) (P = 0.046). Weaker tumor PTH mRNA level was significantly associated with higher concentration of circulating 25-hydroxyvitamin D (P = 0.005). No significant correlation was seen between PTH immunoreactivity and patient biochemistry. Tumor weight was strongly associated with circulatory concentrations of calcium and PTH. Conclusions No areas with apparently higher PTH expression were identified, perhaps suggesting that hyper functioning parathyroid tumor subclones should be rare. Circulating 25-hydroxyvitamin D levels may influence tumor PTH expression in vivo. If PTH immunoreactivity reflects the tumor calcium–PTH set point, our data imply that the main determinant of disease severity should be tumor weight. PMID:26865585

  14. Intrathyroidal parathyroid adenoma: preoperative identification and localization by parathyroid imaging

    SciTech Connect

    Al-Suhaili, A.R.; Lynn, J.; Lavender, J.P.

    1988-07-01

    The authors report, probably for the first time, a successful pre-operative localization of 7 mm intrathyroidal parathyroid adenoma which was successfully removed by using parathyroid imaging using a dual tracer (T1-201 and Tc-99m) and subtraction technique.

  15. Negative Association between Serum Parathyroid Hormone Levels and Urinary Perchlorate, Nitrate, and Thiocyanate Concentrations in U.S. Adults: The National Health and Nutrition Examination Survey 2005–2006

    PubMed Central

    Ko, Wen-Ching; Liu, Chien-Liang; Lee, Jie-Jen; Liu, Tsang-Pai; Yang, Po-Sheng; Hsu, Yi-Chiung; Cheng, Shih-Ping

    2014-01-01

    Objectives Perchlorate, nitrate, and thiocyanate are well-known inhibitors of the sodium-iodide symporter and may disrupt thyroid function. This exploratory study investigated the association among urinary perchlorate, nitrate, and thiocyanate concentrations and parathyroid hormone (PTH) levels in the general U.S. population. Methods We analyzed data on 4265 adults (aged 20 years and older) from the National Health and Nutrition Examination Survey in 2005 through 2006 to evaluate the relationship among urinary perchlorate, nitrate, and thiocyanate concentration and PTH levels and the presence of hyperparathyroidism cross-sectionally. Results The geometric means and 95% confidence interval (95% CI) concentrations of urinary perchlorate, nitrate, and thiocyanate were 3.38 (3.15–3.62), 40363 (37512–43431), and 1129 (1029–1239) ng/mL, respectively. After adjusting for confounding variables and sample weights, creatinine-corrected urinary perchlorate was negatively associated with serum PTH levels in women (P = 0.001), and creatinine-corrected urinary nitrate and thiocyanate were negatively associated with serum PTH levels in both sex groups (P = 0.001 and P<0.001 for men, P = 0.018 and P<0.001 for women, respectively). Similar results were obtained from sensitivity analyses performed for exposure variables unadjusted for creatinine with urinary creatinine added as a separate covariate. There was a negative relationship between hyperparathyroidism and urinary nitrate and thiocyanate [odds ratio (95% CI) = 0.77 (0.60–0.98) and 0.69 (0.61–0.79), respectively]. Conclusions A higher urinary concentration of perchlorate, nitrate, and thiocyanate is associated with lower serum PTH levels. Future studies are needed to determine the pathophysiological background of the observation. PMID:25514572

  16. Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In spite of a high prevalence of vitamin D inadequacy in pregnant women and neonates, relationships among vitamin D status [25(OH)D], parathyroid hormone (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral content (WBBMC) in the newborn are poorly characterized. The purpose...

  17. Reoperative parathyroid surgery.

    PubMed

    Grant, C S; Charboneau, J W; James, E M; Reading, C C

    1988-05-27

    Reoperation for persistent or recurrent primary hyperparathyroidism immediately connotes a complex clinical management problem. Successful cure of hypercalcemia is less frequent whereas complications are more common compared to initial explorations. Of 212 patients operated on at the Mayo Clinic from 1978 through 1986, 189 (89%) were cured. Sporadic disease, multiple endocrine neoplasia, and familial hyperparathyroidism were found in 183 (87%), 20 (9%), and 9 (4%) patients, respectively. Prior to the most recent reoperation, these patients had undergone from one to five operations. Preoperative localization examinations were performed in 192 patients (91%). Cervical high-resolution, real-time ultrasonography, computed tomography, and thallium-technetium scintigraphy had sensitivity rates of 87%, 56%, and 71%, respectively. When the tumor was localized preoperatively, the operative time and cost were significantly reduced compared to nonlocalized tumors. Cervical reexploration only was required in 154 (72%), combined cervical and mediastinal exploration occurred in 46 (22%), and mediastinal exploration only was performed in 12 (6%). There was no perioperative mortality; permanent hypoparathyroidism developed in 33 patients (16%), and six patients (2.9%) suffered permanent unilateral vocal cord paralysis. Anatomically, the most frequent site to find a missed parathyroid adenoma was in the normal location. The large majority of these glands were removed through a cervical incision although, on occasion, they were retracted from the anterior superior mediastinum or the low tracheoesophageal space. These data confirm that reoperative parathyroid surgery can be performed safely, with a rather high degree of success, but too-frequently results in a lifetime morbidity of hypoparathyroidism.

  18. A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients

    PubMed Central

    Villa-Bellosta, Ricardo; Rodriguez-Osorio, Laura; Mas, Sebastian; Abadi, Younes; Rubert, Mercedes; de la Piedra, Concepción; Gracia-Iguacel, Carolina; Mahillo, Ignacio; Ortiz, Alberto; Egido, Jesús; González-Parra, Emilio

    2017-01-01

    Background The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. Methods We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Results Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101–300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996–0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0–100 pg/ml and 101–300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515–11.27)(p = 0.006). Conclusions In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice. PMID:28339474

  19. Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas

    PubMed Central

    Newey, Paul J.; Nesbit, M. Andrew; Rimmer, Andrew J.; Attar, Moustafa; Head, Rosie T.; Christie, Paul T.; Gorvin, Caroline M.; Stechman, Michael; Gregory, Lorna; Mihai, Radu; Sadler, Greg; McVean, Gil; Buck, David

    2012-01-01

    Context: Genetic abnormalities, such as those of multiple endocrine neoplasia type 1 (MEN1) and Cyclin D1 (CCND1) genes, occur in <50% of nonhereditary (sporadic) parathyroid adenomas. Objective: To identify genetic abnormalities in nonhereditary parathyroid adenomas by whole-exome sequence analysis. Design: Whole-exome sequence analysis was performed on parathyroid adenomas and leukocyte DNA samples from 16 postmenopausal women without a family history of parathyroid tumors or MEN1 and in whom primary hyperparathyroidism due to single-gland disease was cured by surgery. Somatic variants confirmed in this discovery set were assessed in 24 other parathyroid adenomas. Results: Over 90% of targeted exons were captured and represented by more than 10 base reads. Analysis identified 212 somatic variants (median eight per tumor; range, 2–110), with the majority being heterozygous nonsynonymous single-nucleotide variants that predicted missense amino acid substitutions. Somatic MEN1 mutations occurred in six of 16 (∼35%) parathyroid adenomas, in association with loss of heterozygosity on chromosome 11. However, no other gene was mutated in more than one tumor. Mutations in several genes that may represent low-frequency driver mutations were identified, including a protection of telomeres 1 (POT1) mutation that resulted in exon skipping and disruption to the single-stranded DNA-binding domain, which may contribute to increased genomic instability and the observed high mutation rate in one tumor. Conclusions: Parathyroid adenomas typically harbor few somatic variants, consistent with their low proliferation rates. MEN1 mutation represents the major driver in sporadic parathyroid tumorigenesis although multiple low-frequency driver mutations likely account for tumors not harboring somatic MEN1 mutations. PMID:22855342

  20. Parathyroid hormone (PTH) blood test

    MedlinePlus

    ... in the blood Radiation to the parathyroid glands Sarcoidosis Excess vitamin D intake Other conditions for which ... I Multiple endocrine neoplasia (MEN) II Osteomalacia Rickets Sarcoidosis Review Date 10/28/2015 Updated by: Brent ...

  1. Optical Characterization of Parathyroid Tissues.

    PubMed

    Brandao, M P; Iwakura, R; Honorato-Sobrinho, A A; Haleplian, K; Ito, A S; de Freitas, L C Conti; Bachmann, L

    2016-07-05

    The parathyroid glands are small and often similar to lymph nodes, fat, and thyroid tissue. These glands are difficult to identify during surgery and a biopsy of the parathyroid for identification can lead to damage of the gland. The use of static and time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and nondestructive method to assist medical evaluation of parathyroid tissues. In this study, we investigated 10 human parathyroid samples by absorbance, fluorescence, excitation, and time-resolved fluorescence measurements. Moreover, we compared the results of time-resolved fluorescence measurements with 59 samples of thyroid tissues. The fluorescence lifetimes with emission at 340 nm were 1.09 ± 0.10 and 4.46 ± 0.06 ns for healthy tissue, 1.01 ± 0.25 and 4.39 ± 0.36 ns for benign lesions, and 0.67 ± 0.36 and 3.92 ± 0.72 ns for malignant lesions. The lifetimes for benign and malignant lesions were significantly different, as attested by the analysis of variance with confidence levels higher than 87%. For each class of samples (healthy, benign, and malignant) we perceived statistical differences between the thyroid and parathyroid tissue, independently. After further investigations, fluorescence methods could become a tool to identify normal and pathological parathyroid tissues and distinguish thyroid from parathyroid tissues.

  2. Epigenetic Alterations in Parathyroid Cancers

    PubMed Central

    Verdelli, Chiara; Corbetta, Sabrina

    2017-01-01

    Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile. PMID:28157158

  3. Epigenetic Alterations in Parathyroid Cancers.

    PubMed

    Verdelli, Chiara; Corbetta, Sabrina

    2017-02-01

    Parathyroid cancers (PCas) are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH); consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile.

  4. Parathyroid Disorders - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Parathyroid Disorders URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Parathyroid Disorders - Multiple Languages To use the sharing features ...

  5. Parathyroid hormone-related protein blood test

    MedlinePlus

    ... gov/ency/article/003691.htm Parathyroid hormone-related protein blood test To use the sharing features on ... page, please enable JavaScript. The parathyroid hormone-related protein (PTH-RP) test measures the level of a ...

  6. Octreotide Uptake in Parathyroid Adenoma

    PubMed Central

    Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime

    2012-01-01

    The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397

  7. Pathology of the parathyroid glands in hyperparathyroidism.

    PubMed

    Baloch, Zubair W; LiVolsi, Virginia A

    2013-08-01

    This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

  8. Retropharyngeal thymus and parathyroid gland: a case report.

    PubMed

    Schramm, Jordan C; Perry, Deborah A; Sewell, Ryan K

    2014-01-01

    Cervical ectopic thymus occurs when thymic tissue arrests during its embryologic descent through the neck to the upper mediastinum. Most often it presents as an asymptomatic neck mass. Rarely does it present with airway compromise, particularly in neonates. A neonate presented with a retropharyngeal mass causing dynamic upper airway obstruction, mimicking a venolymphatic malformation. Ultimately this proved to be aberrant ectopic thymus with an associated parathyroid gland. While there have been isolated reports of thymus or parathyroid in the retropharyngeal space, none of the prior reports found both within the same patient.

  9. Parathyroid-specific interaction of the calcium-sensing receptor and G alpha q.

    PubMed

    Pi, Min; Chen, Ling; Huang, MinZhao; Luo, Qiang; Quarles, L Darryl

    2008-12-01

    The calcium-sensing receptor regulates various parathyroid gland functions, including hormone secretion, gene transcription, and chief cell hyperplasia through G alpha q- and G alpha i-dependent signaling pathways. To determine the specific function of G alpha q in these processes, we generated transgenic mice using the human parathyroid hormone promoter to drive overexpression of a dominant negative G alpha q loop minigene to selectively disrupt G alpha q function in the parathyroid gland. The G alpha q loop mRNA was highly expressed in the parathyroid gland but not in other tissues of these transgenic mice. Gross appearance, body weight, bone mineral density, and survival of the transgenic mice were indistinguishable from those of their wild-type littermates. Adult transgenic mice, however, exhibited an increase in parathyroid hormone mRNA and in its basal serum level as well as in gland size. The response of the parathyroid gland to hypocalcemia was found to be reduced in sensitivity in the transgenic mice when compared to their wild-type controls. Abnormalities of the parathyroid gland function in these transgenic mice were similar to those of heterozygous G alpha q(+/-) and calcium sensing receptor(+/-) mice. These studies demonstrate the feasibility of selectively targeting the parathyroid gland to investigate signaling mechanisms downstream of the calcium receptor.

  10. The parathyroid gland in health and disease.

    PubMed Central

    Ghandur-Mnaymneh, L.; Cassady, J.; Hajianpour, M. A.; Paz, J.; Reiss, E.

    1986-01-01

    The authors studied the parathyroid glands from 100 previously healthy subjects who died suddenly and were admitted to the Dade County Medical Examiner's (ME) morgue and from 66 inpatients who died at Jackson Memorial Hospital (JMH). Parathyroid glands in patients with diseases (JMH series) were heavier than those in healthy persons (ME series), and both groups of glands were significantly heavier than those previously reported. Mean glandular weight in white subjects was 42.6 +/- 20.3 mg, with a range of 22-103 mg. The 95% upper limit of gland weight for healthy white subjects was 73.1 mg and for black subjects, 91.6 mg. The size and weight exhibited a skewed distribution. Gland weight varied with age, increasing to a maximum in the 41-60 year old age group in all subsets except white women, in whom it continued to increase till after age 70. There was slight correlation (r2 = 0.15) of gland weight with body weight within series and race groups; parenchymal content of the glands was not constant but correlated positively with glandular weight. Glands from both series had a comparable fat content. Fat was unevenly distributed throughout the gland, and its amount was highly variable, ranging between 0 and 90%, with a mean of 26% for white subjects and 24% for black subjects in both series. Therefore, percentage fat may not be used as an index of hyperplasia. Healthy back subjects had heavier glands than healthy white subjects, unaccounted for by differences in body weights; this difference was not statistically significant in subjects with disease. Within the black race, glands were not significantly heavier in disease than in health, and in the few cases with serum calcium determinations, the gland weight did not vary inversely with serum calcium levels as in white subjects, suggesting a basic difference in parathyroid calcium metabolism between the two races. PMID:3789088

  11. The relationship between total mass and blood supply of parathyroid glands and their secretion of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.

    PubMed

    Ahmadi, Farrokhlagha; Aghajanzadeh, Pegah; Yazdi, Hadi Rokni; Maziar, Sima; Gatmiri, Sayad Mansour

    2016-03-01

    Characteristics of parathyroid glands usually determined by ultrasonography such as its total weight or volume might be a good indicator for the induction or suppression of parathyroid hormone (PTH) secretion from these glands. In the present study, we investigated the relationship between the volume and blood supply grade of the parathyroid glands, and its PTH secretion. Study subjects included 52 consecutive patients with the secondary hyperparathyroidism undergoing maintenance hemodialysis therapy referred to dialysis wards of the Imam Khomeini and Amiralam University Hospitals in Tehran. Serum intact PTH (i-PTH) was measured by an ELISA assay. The parathyroid glands characteristics were identified by ultrasonography that was performed simultaneously with blood collection. Parathyroid blood flows were evaluated by power-Doppler color imaging. There was no significant correlation between the total mass of the glands and serum concentration of i-PTH. No significant correlations were also observed between both total central and peripheral parathyroid glands blood flow and serum i-PTH level. Dialysis duration and serum alkaline phosphatase were significantly correlated in a positive manner with i-PTH level. Furthermore, serum level of i-PTH was not correlated with the total signals of glands blood flow in a multivariable linear regression analysis. Serum secreted i-PTH level might not be predictable by a total mass of parathyroid glands as well as their blood supply.

  12. Expression of parathyroid-specific genes in vascular endothelial progenitors of normal and tumoral parathyroid glands.

    PubMed

    Corbetta, Sabrina; Belicchi, Marzia; Pisati, Federica; Meregalli, Mirella; Eller-Vainicher, Cristina; Vicentini, Leonardo; Beck-Peccoz, Paolo; Spada, Anna; Torrente, Yvan

    2009-09-01

    Parathyroid tissue is able to spontaneously induce angiogenesis, proliferate, and secrete parathyroid hormone when autotransplanted in patients undergoing total parathyroidectomy. Angiogenesis is also involved in parathyroid tumorigenesis. Here we investigated the anatomical and molecular relationship between endothelial and parathyroid cells within human parathyroid glands. Immunohistochemistry for CD34 antigen identified two subpopulations in normal and tumoral parathyroid glands: one constituted by cells lining small vessels that displayed endothelial antigens (factor VIII, isolectin, laminin, CD146) and the other constituted of single cells scattered throughout the parenchyma that did not express endothelial markers. These parathyroid-derived CD34(+) cells were negative for the hematopoietic and mesenchymal markers CD45, Thy-1/CD90, CD105, and CD117/c-kit; however, a subset of CD34(+) cells co-expressed the parathyroid specific genes glial cell missing B, parathyroid hormone, and calcium sensing receptor. When cultured, these cells released significant amount of parathyroid hormone. Parathyroid-derived CD34(+) cells, but not CD34(-) cells, proliferated slowly and differentiated into mature endothelial cells. CD34(+) cells from parathyroid tumors differed from those derived from normal parathyroid glands as: 1) they were more abundant and mainly scattered throughout the parenchyma; 2) they rarely co-expressed CD146; and 3) a fraction co-expressed nestin. In conclusion, we identified cells expressing endothelial and parathyroid markers in human adult parathyroid glands. These parathyroid/endothelial cells were more abundant and less committed in parathyroid tumors compared with normal glands, showing features of endothelial progenitors, which suggests that they might be involved in parathyroid tumorigenesis.

  13. Parathyroid score can predict the duration of required calcium supplementation after total thyroidectomy

    PubMed Central

    Kim, Soo Young; Lee, Yong Sang; Kim, Seok-Mo; Chang, Hang-Seok; Park, Cheong Soo

    2017-01-01

    Background Postoperative hypoparathyroidism is the most common complication after total thyroidectomy, owing to unintentional injury or decreased blood flow to the parathyroid glands. Prediction of postoperative hypoparathyroidism would be helpful for surgeons to manage postoperative hypocalcemia. In this study, we scored the discoloration of the parathyroid glands using a new parathyroid scoring system and evaluated the correlation between the parathyroid score and duration of required calcium supplementation after total thyroidectomy. Methods A total of 316 patients undergoing total thyroidectomy between November 2009 and April 2010 were enrolled in this retrospective study. Parathyroid scoring was performed by one experienced surgeon. The status of each of the 4 parathyroid glands was classified as normal color (3 points), slightly discolored (2 points), dark discoloration (1 point), or loss of the gland (0 points), resulting in possible total scores of 0–12. Serum parathyroid hormone (PTH), serum calcium, and ionized calcium concentrations were measured at 2 hours, 2 weeks, 3 months, 6 months, and 1 year after surgery. Patients were also divided into three groups based on the duration of required calcium supplementation: no required supplementation (n = 260, 82.3%), required supplementation for <6 months (n = 38, 12%), and required supplementation for ≥6 months (n = 18, 5.75%). Results Parathyroid scores were positively correlated with ionized PTH concentrations at 2 hours (r = 0.053, p < 0.001), 2 weeks (r = 0.056, p < 0.001), 3 months (r = 0.032, p<0.001), 6 months (r = 0.072, p < 0.001), and 1 year (r = 0.071, p < 0.001) after thyroidectomy. Parathyroid scores were significantly and inversely associated with the duration of required calcium supplementation (p = 0.001). Conclusions Parathyroid scores at the end of surgery might be helpful for predicting the degree of postoperative hypocalcemia after total thyroidetomy. PMID:28350886

  14. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro.

    PubMed

    Horiuchi, N; Caulfield, M P; Fisher, J E; Goldman, M E; McKee, R L; Reagan, J E; Levy, J J; Nutt, R F; Rodan, S B; Schofield, T L

    1987-12-11

    One mechanism considered responsible for the hypercalcemia that frequently accompanies malignancy is secretion by the tumor of a circulating factor that alters calcium metabolism. The structure of a tumor-secreted peptide was recently determined and found to be partially homologous to parathyroid hormone (PTH). The amino-terminal 1-34 region of the factor was synthesized and evaluated biologically. In vivo it produced hypercalcemia, acted on bone and kidney, and stimulated 1,25-dihydroxy-vitamin D3 formation. In vitro it interacted with PTH receptors and, in some systems, was more potent than PTH. These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia.

  15. Spontaneous proliferative and neoplastic lesions in thyroid and parathyroid glands of nondomestic felids.

    PubMed

    Pope, Jenny P; Steeil, James; Ramsay, Edward C; Reel, Danielle; Newman, Shelley J

    2017-01-01

    Based on microscopic and immunohistochemical characterization, we documented spontaneous proliferative and neoplastic lesions in the thyroid and parathyroid glands of nondomestic felids. Ten animals (4 leopards, 3 tigers, and 3 cougars), all with a previous diagnosis of thyroid neoplasia were identified from the University of Tennessee College of Veterinary Medicine database. The mean age of affected animals was 15.9 y. Twelve neoplasms were identified; 2 animals had 2 concurrent neoplasms. After immunohistochemical characterization using a panel of chromogranin A, thyroglobulin, and calcitonin, 7 of the former thyroid neoplasms were diagnosed as thyroid adenomas, 1 was diagnosed as a thyroid carcinoma, and 4 were diagnosed as parathyroid adenomas. No thyroid medullary neoplasms (C-cell tumors) were diagnosed in the current study. Most of the diagnosed neoplasms were benign (11 of 12), and metastasis was not documented in the single carcinoma. Only 2 animals were suspected to have functional neoplasms (1 thyroid adenoma and 1 parathyroid adenoma), based on associated tissue lesions or serum biochemistry. Other documented lesions in the thyroid and parathyroid glands included thyroid nodular hyperplasia ( n = 7), parathyroid hyperplasia associated with chronic renal disease ( n = 2), a thyroid abscess, and a branchial cyst. Parathyroid adenomas were more commonly diagnosed than expected in comparison with domestic cats. We demonstrated that an immunohistochemistry panel for thyroglobulin, calcitonin, and chromogranin A can be used to differentiate neoplasms of thyroid from parathyroid origin in nondomestic felids.

  16. Intrathyroidal parathyroid hyperplasia in tertiary hyperparathyroidism

    PubMed Central

    Kim, Byung Seup; Ryu, Han Suk; Kang, Kyung Ho; Park, Sung Jun

    2013-01-01

    We report herein a case of intrathyroidal parathyroid hyperplasia in a patient with tertiary hyperparathyroidism. The patient was recommended for parathyroidectomy due to sustained hypercalcemia after kidney transplantation. Preoperative radiologic evaluations showed a benign-looking thyroid mass and three enlarged parathyroid glands. Intraoperative intact parathyroid hormone (iPTH) level and frozen biopsy results indicated a missed parathyroid gland after immediate subtotal parathyroidectomy. Then, a secondary partial resection of thyroid including the thyroid nodule was performed. An excised intrathyroid nodule was diagnosed to be parathyroid hyperplasia by frozen biopsy, and intraoperative iPTH level abruptly decreased. A benign-looking thyroidal mass in patients with secondary or tertiary hyperparathyroidism should be carefully evaluated considering the possibility of an intrathyroidal parathyroid hyperplasia. PMID:24964443

  17. Original Research: Atorvastatin prevents rat cardiomyocyte hypertrophy induced by parathyroid hormone 1-34 associated with the Ras-ERK signaling.

    PubMed

    Liu, Xiaogang; Zou, Chunbo; Yu, Chengyuan; Xie, Rujuan; Sui, Manshu; Mu, Suhong; Li, Li; Zhao, Shilei

    2016-10-01

    We investigated the effects of atorvastatin (Ator) on cardiomyocyte hypertrophy (CMH) induced by rat parathyroid hormone 1-34 (PTH1-34) and Ras-extracellular signal regulated protein kinases 1/2 (ERK1/2) signaling. Rat cardiomyocytes were randomly divided into seven groups: normal controls (NC), PTH1-34 (10(-7) mol/L), Ator (10(-5) mol/L), farnesyl transferase inhibitors-276 (FTI-276, 4 × 10(-5) mol/L), PTH1-34 + Ator, PTH1-34 + FTI-276 and PTH1-34 + Ator + mevalonic acid (MVA, 10(-4) mol/L). After treatment, the hypertrophic responses of cardiomyocytes were assessed by measuring cell diameter, detecting protein synthesis, and single-cell protein content. The concentrations of hypertrophic markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured by ELISA. Protein expressions of ERK1/2, p-ERK1/2 and Ras were detected by western blotting. The results showed that compared with the PTH1-34 group, cellular diameter, 3H-leucine incorporation, single-cell protein content, ANP and BNP concentration decreased by 12.07 µm, 1622 cpm/well, 84.34 pg, 7.13 ng/L and 20.04 µg/L, respectively, and the expressions of Ras and p-ERK1/2 were downregulated in PTH1-34 + Ator group (P < 0.05). Compared to the PTH1-34 + Ator group, the corresponding hypertrophic responses and hypertrophic markers increased by 4.95 µm, 750 cpm/well, 49.08 pg, 3.12 ng/L and 9.35 µg/L, respectively, and the expressions of Ras and p-ERK1/2 were upregulated in the PTH1-34 + Ator + MVA group (P < 0.05). In conclusion, Ator prevents neonatal rat CMH induced by PTH1-34 and Ras-ERK signaling may be involved in this process.

  18. Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary Hyperparathyroidism.

    PubMed

    Shilo, Vitali; Mor-Yosef Levi, Irit; Abel, Roy; Mihailović, Aleksandra; Wasserman, Gilad; Naveh-Many, Tally; Ben-Dov, Iddo Z

    2017-03-15

    Secondary hyperparathyroidism commonly complicates CKD and associates with morbidity and mortality. We profiled microRNA (miRNA) in parathyroid glands from experimental hyperparathyroidism models and patients receiving dialysis and studied the function of specific miRNAs. miRNA deep-sequencing showed that human and rodent parathyroids share similar profiles. Parathyroids from uremic and normal rats segregated on the basis of their miRNA expression profiles, and a similar finding was observed in humans. We identified parathyroid miRNAs that were dysregulated in experimental hyperparathyroidism, including miR-29, miR-21, miR-148, miR-30, and miR-141 (upregulated); and miR-10, miR-125, and miR-25 (downregulated). Inhibition of the abundant let-7 family increased parathyroid hormone (PTH) secretion in normal and uremic rats, as well as in mouse parathyroid organ cultures. Conversely, inhibition of the upregulated miR-148 family prevented the increase in serum PTH level in uremic rats and decreased levels of secreted PTH in parathyroid cultures. The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism indicates their importance for parathyroid function and the development of hyperparathyroidism. Specifically, let-7 and miR-148 antagonism modified PTH secretion in vivo and in vitro, implying roles for these specific miRNAs. These findings may be utilized for therapeutic interventions aimed at altering PTH expression in diseases such as osteoporosis and secondary hyperparathyroidism.

  19. Activator Protein 2α Mediates Parathyroid TGF-α Self-Induction in Secondary Hyperparathyroidism

    PubMed Central

    Arcidiacono, Maria Vittoria; Cozzolino, Mario; Spiegel, Noah; Tokumoto, Masanori; Yang, Jing; Lu, Yan; Sato, Tetsuhiko; Lomonte, Carlo; Basile, Carlo; Slatopolsky, Eduardo; Dusso, Adriana S.

    2008-01-01

    In secondary hyperparathyroidism, enhanced expression of TGF-α in the parathyroid leads to its own upregulation, generating a feed-forward loop for TGF-α activation of its receptor, EGFR receptor (EGFR), which promotes parathyroid hyperplasia. These studies examined the role of activator protein 2α (AP2), an inducer of TGF-α gene transcription, in the upregulation of parathyroid TGF-α in secondary hyperparathyroidism. In rat and human secondary hyperparathyroidism, parathyroid AP2 expression strongly correlated with TGF-α levels and with the rate of parathyroid growth, as expected. Furthermore, the increases in rat parathyroid content of AP2 and its binding to a consensus AP2 DNA sequence preceded the increase in TGF-α induced by high dietary phosphate. More significant, in A431 cells, which provide a model of enhanced TGF-α and TGF-α self-induction, mutating the core AP2 site of the human TGF-α promoter markedly impaired promoter activity induced by endogenous or exogenous TGF-α. Important for therapy, in five-sixths nephrectomized rats fed high-phosphate diets, inhibition of parathyroid TGF-α self-induction using erlotinib, a highly specific inhibitor of TGF-α/EGFR-driven signals, reduced AP2 expression dosage dependently. This suggests that the increases in parathyroid AP2 occur downstream of EGFR activation by TGF-α and are required for TGF-α self-induction. Indeed, in A431 cells, erlotinib inhibition of TGF-α self-induction caused parallel reductions in AP2 expression and nuclear localization, as well as TGF-α mRNA and protein levels. In summary, increased AP2 expression and transcriptional activity at the TGF-α promoter determine the severity of the hyperplasia driven by parathyroid TGF-α self-upregulation in secondary hyperparathyroidism. PMID:18579641

  20. An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma

    PubMed Central

    Mishra, Ankur; Newman, David

    2014-01-01

    Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology. PMID:24959180

  1. Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis

    PubMed Central

    2013-01-01

    Background Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies. Methods We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels. Results A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89). Conclusions Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates. PMID:23594621

  2. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  3. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  4. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  5. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Parathyroid hormone test system. 862.1545 Section... Systems § 862.1545 Parathyroid hormone test system. (a) Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma....

  6. Evidence-Based Workflows for Thyroid and Parathyroid Surgery

    PubMed Central

    Meltzer, Charles; Budayr, Amer; Chavez, Annette; Dlott, Richard; Greif, William; Gurushanthaiah, Deepak; Klonecke, Andrew; Lando, Matthew; Leary, Joyce; Nayak, Sundeep; Niederkohr, Ryan; Park, Judith; Savitz, Alison; Schwartz, Henry

    2016-01-01

    A need exists to reduce care variations by standardizing the practice of thyroid and parathyroid surgery. During the course of a year, a task force developed algorithms representing decision points and workflows based on American Thyroid Association guidelines and three internal studies of surgical practices in the Northern and Southern California Regions of Kaiser Permanente conducted in collaboration with Health Information Technology Transformation & Analytics (HITTA). PMID:27479948

  7. Absence of RET proto-oncogene abnormalities in sporadic parathyroid tumors

    SciTech Connect

    Pausova, Z.; Janicic, N.; Konrad, E.

    1994-09-01

    Parathyroid tumors can occur either sporadically or as a part of inherited cancer syndromes such as multiple endocrine neoplasia (MEN) type 2A. Recently, development of this syndrome has been shown to be related to specific mutations in the RET proto-oncogene, a putative receptor tyrosine kinase. Activation of this proto-oncogene has been demonstrated not only in tumors of the MEN 2A syndrome, but also in other neoplasia of neuroectoderm origin, namely papillary thyroid carcinoma where a rearrangement of the RET proto-oncogene has been found. In the present study, a role of the RET proto-oncogene in the development of sporadic parathyroid tumors was investigated by analyzing DNA samples obtained from 13 parathyroid adenomas and 6 parathyroid hyperplasias. Southern blot, using BamHI restricted DNA, did not reveal any gross alteration of the gene. Polymerase chain reaction (PCR) was then employed to amplify DNA fragments corresponding to exons 10 and 11 in which all MEN 2A mutations have been identified. Amplified DNA fragments were all of expected size (exon 10, 182 bp; exon 11, 233 bp). Since a single point mutation at codon 634 has been found to be associated in close to 90% of cases with development of parathyroid tumors in patients with the MEN 2A syndrome, exon 11, containing this codon, was further examined by direct sequence analysis. Sequences obtained from all tumors tested, however, did not differ from the wild type sequence. Therefore, the mutation of the RET proto-oncogene commonly associated with parathyroid neoplasias in MEN 2A is uncommon in sporadic parathyroid tumors. This suggests that the pathogenesis of parathyroid tumors occurring sporadically may be different from those occurring in patients with the MEN 2A syndrome.

  8. Parathyroid autotransplantation in rats having hypoparathyroidism

    PubMed Central

    Erikoglu, Mehmet; Colak, Bayram; Toy, Hatice; Gurbilek, Mehmet

    2015-01-01

    Re-implantation techniques of extracted parathyroid tissue were developed in order to prevent temporary hypocalcemia. During thyroid surgery; inadvertently removed or devascularized parathyroid gland is usually implanted in the sternocleidomastoid muscle. In this experimental study using rats with hypoparathyroidism, our aim was to investigate whether the excised parathyroid tissue could be seeded in the liver and in the peritoneum, instead of the SCM muscle. In our study, four different groups, each consisting of 10 Wistar albino rats were used (Control group, sternocleidomastoid muscle group, liver group, peritoneum group). Parathyroidectomy was performed and the parathyroid tissue was seeded into the sternocloid mastoid muscle, liver and peritoneum. After 14 days, the rats were sacrificed and levels of calcium, magnesium, phosphorus, alkaline phosphatase and parathyroid hormone were measured in rats’ blood samples. The autotransplanted parathyroid tissue was then excised and examined. In all groups, parathyroid tissues were analyzed histopathologically according to calcification, necrosis, tissue loss, foreign body reaction, inflammation and fibrosis. Regarding Ca, Mg, PO4, ALP; There were no difference between the groups. When we compared control group with the other groups; a difference was observed in the levels of PTH (P<0.05). In pathological examination; regarding tissue loss; there was a difference between liver and peritoneum groups (P<0.05). In our study, we expected better result in plantings inside liver and peritone compared to SKM. However, there were no difference between the groups. PMID:26629152

  9. WR-2721 inhibits parathyroid adenylate cyclase

    SciTech Connect

    Weaver, M.E.; Morrissey, J.; McConkey, C. Jr.; Goldfarb, S.; Slatopolsky, E.; Martin, K.J.

    1987-02-01

    WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) is a chemoprotective and radioprotective agent that has been shown to lower serum calcium in dogs and in humans. This is secondary both to impaired release of CaS from bone and diminished secretion of parathyroid hormone (PTH) from parathyroid glands. Because cAMP plays a role in the regulation of PTH secretion and WR-2721 has been shown to lower cAMP levels in radiated mouse spleen, the authors investigated the effects of WR-2721 on cAMP production in dispersed bovine parathyroid cells. Additional, they studied the adenylate cyclase in plasma membranes from normal bovine parathyroid glands after exposure to WR-2721. With parathyroid cells incubated at 0.5 mM CaS , addition of Wr-2721 in concentrations ranging from 0.02 to 2.0 mM resulted in a progressive decrease in intracellular cAMP measured by radioimmunoassay. In plasma membranes of bovine parathyroid cells a dose-dependent decrease in adenylate cyclase activity was noted. Inhibition of the cyclase was seen over a wide range of MgS concentrations. WR-2721 inhibited both basal and NaF, Gpp(NH)(, forskolin, and pertussin toxin-stimulated adenylate cyclase. These data suggest that WR-2721 inhibits the activity of parathyroid adenylate cyclase.

  10. Enhanced identification and functional protective role of carbon nanoparticles on parathyroid in thyroid cancer surgery

    PubMed Central

    Shi, Chenlei; Tian, Bo; Li, Shengze; Shi, Tiefeng; Qin, Huadong; Liu, Shaoyan

    2016-01-01

    Abstract The aim of this study was to determine the effects of nanocarbon particles in combination with meticulous capsular dissection on enhancing the identification and protecting the function of parathyroid glands in thyroid cancer surgery. The data of 97 patients with papillary thyroid tumors diagnosed and treated at the Second Affiliated Hospital, Harbin Medical University between January 2014 and February 2015 were reviewed. Data regarding the sex, age, calcium and parathyroid hormone (PTH) levels, tumor size, multifocality, T stage, and extrathyroid invasion were collected. The incidence of surgeries in which the parathyroid glands were cut mistakenly, the concentration of serum calcium and parathyroid hormone before surgery (baseline) and after surgery on days 1, 3, and 7, and 1 and 6 months in the patients of the two groups (the nanocarbon and control groups) were analyzed. Fifty-two patients underwent meticulous capsular dissection combined with nanocarbon treatment (nanocarbon group), and 45 underwent meticulous capsular dissection alone (control group). The nanocarbon group showed a significantly higher total and average number of revealed parathyroid glands (average number is the mean for different individuals have different number) and a lower incidence of the parathyroid glands being mistakenly cut, in addition to a lower level of hypoparathyroidism than control group following surgery (P < 0.05). Serum calcium and PTH levels were significantly lower in patients from both groups after surgery on days 1, 3, and 7 and after 1 month, compared with the preoperative levels (P < 0.05). Compared with the control group, the serum calcium and PTH levels were significantly higher in the nanocarbon group after surgery on days 1, 3, 7, than in the control group. Treatment with nanocarbon in combination with meticulous capsular dissection can significantly facilitate the identification of the parathyroid in thyroid cancer surgery, reduce the risk of

  11. Haemangioma of the parathyroid gland. Does it really exist?

    PubMed

    Svec, Alexandr; Bury, Yvonne

    2010-09-01

    We are reporting a case of a capillary haemangioma-like proliferation arising within a parathyroid gland adenoma, associated with primary hyperparathyroidism. The vessel proliferation bearing a close resemblance to a capillary haemangioma consisted of tightly packed capillaries, endothelial buds and occasional small caliber muscle-containing vessels. The observation expands the spectrum of tumour-associated vascular proliferations by adding an exuberant haemangioma-like pattern to its extreme end. These are a heterogeneous group of lesions reportedly induced by aberrant production of angiogenic factors. We investigated expression of VEGF, pKDR, FGF2, HIF1alpha and HIF2alpha and only VEGF gave a strong positive reaction in the adenoma cells entrapped in the vascular meshwork. Although this does not constitute a proof that aberrant VEGF production was a causative agent, unexpected supportive evidence for its pathogenic role emerged from a failure to detect chromogranin A. Chromogranin A is a precursor of several regulatory proteins, including vasostatin I, a multilevel suppressor of VEGF. The production of vasostatin I may have been reduced in a chromogranin A-negative adenoma which could lead to a loss of its opposing effect on VEGF-regulated processes. The only two other published cases of haemangioma of the parathyroid gland were reported in patients diagnosed with primary parathyroid hyperplasia with hyperparathyroidism, a pathophysiologic condition similar to our case. Therefore we raise the question whether these tumours could also represent a reactive phenomenon.

  12. Parathyroid cysts: the Latin-American experience

    PubMed Central

    Aristizábal, Natalia; Aguilar, Carolina; Palacios, Karen; Pérez, Juan Camilo; Vélez-Hoyos, Alejandro; Duque, Carlos Simon; Sanabria, Alvaro

    2016-01-01

    Background Parathyroid cyst is an infrequent and unsuspected disease. There are more than 300 hundred cases reported in the world literature, a few of them are from Latin America. The experience of our centers and a review of the cases are presented. Methods Case report of a series of patients with parathyroid cyst from our institutions according to the CARE guidelines (Case Reports). A search of Medline, Embase, BIREME (Biblioteca Regional de Medicina) LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), Google Scholar and Scielo (Scientific Electronic Library on Line) databases and telephonic or email communications with other experts from Latin-America was performed . Results Six patients with parathyroid cyst were found in our centers in Colombia. Most of them were managed with aspiration of the cyst. Two of them required surgery. Only one case was functional. Twelve reports from Latin America were found for a total of 18 cases in our region adding ours. Conclusions Parathyroid cysts are uncommonly reported in Latin America. Most of them are diagnosed postoperatively. Suspicion for parathyroid cyst should be raised when a crystal clear fluid is aspirated from a cyst. The confirmation of the diagnosis may be easily done if parathyroid hormone (PTH) level is measured in the cyst fluid. PMID:28149800

  13. Parathyroid ultrasonography: the evolving role of the radiologist

    PubMed Central

    Sung, Jin Yong

    2015-01-01

    Previously, radiologists played a limited role in the treatment of parathyroid disease, primary focusing on the preoperative localization of parathyroid lesions responsible for hyperparathyroidism. But, the widespread use of high-resolution ultrasound has lead to the increasing detection of parathyroid incidentalomas (PTIs). Consequently, radiologists may be required to differentiate PTIs from thyroid lesions, which is most reliably accomplished through the fine needle aspiration-parathyroid hormone analysis. Various nonsurgical treatment modalities for hyperfunctioning parathyroid lesions have been developed with some efficacy. Especially for symptomatic nonfunctioning parathyroid cysts, simple aspiration is a first-line procedure for diagnosis and treatment, while ethanol ablation is a subsequent treatment modality for recurrent cases. PMID:25971897

  14. Parathyroid hormone and bone healing.

    PubMed

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-07-01

    Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

  15. REFERENCE RANGE FOR SERUM PARATHYROID HORMONE

    PubMed Central

    Aloia, John F.; Feuerman, Martin; Yeh, James K.

    2006-01-01

    Objective To determine whether the reference range for parathyroid hormone (PTH) should be lowered (from 65 pg/mL to a proposed value of 46 pg/mL) with use of the Allegro radioimmunometric assay. Methods We examined the reference range for PTH, adjusted for serum 25-hydroxyvitamin D (25-OHD), in 503 healthy African American and white women, who were 20 to 80 years old. We also analyzed other factors that are thought to influence PTH levels. Results Univariate predictors of PTH were identified, and a multivariate model was developed with use of the variables and PTH. Serum PTH was significantly higher in black study subjects than in white study subjects (P<0.02). Increasing PTH was also significantly correlated with increasing body mass index, age, and serum creatinine and with decreasing dietary calcium intake and serum 25-OHD levels. A stepwise multiple linear regression analysis yielded the following predictors of PTH: body mass index (R2 = 9.4%), age (R2 = 1.0%), and serum 25-OHD (R2 = 0.8%). In our study population, many PTH values were above the proposed new upper limit of 46 pg/mL. Conclusion The upper limit of the reference range for serum PTH should not be changed. Factors to be considered in analysis of serum PTH values in the upper reference range in patients with normocalcemia include obesity, race, 25-OHD levels, advanced age, serum creatinine, and dietary calcium intake. PMID:16690460

  16. Factors associated with latent fingerprint exclusion determinations.

    PubMed

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2017-02-22

    Exclusion is the determination by a latent print examiner that two friction ridge impressions did not originate from the same source. The concept and terminology of exclusion vary among agencies. Much of the literature on latent print examination focuses on individualization, and much less attention has been paid to exclusion. This experimental study assesses the associations between a variety of factors and exclusion determinations. Although erroneous exclusions are more likely to occur on some images and for some examiners, they were widely distributed among images and examiners. Measurable factors found to be associated with exclusion rates include the quality of the latent, value determinations, analysis minutia count, comparison difficulty, and the presence of cores or deltas. An understanding of these associations will help explain the circumstances under which errors are more likely to occur and when determinations are less likely to be reproduced by other examiners; the results should also lead to improved effectiveness and efficiency of training and casework quality assurance. This research is intended to assist examiners in improving the examination process and provide information to the broader community regarding the accuracy, reliability, and implications of exclusion decisions.

  17. FGF23 and the parathyroid glands.

    PubMed

    Silver, Justin; Naveh-Many, Tally

    2010-11-01

    Fibroblast growth factor 23 (FGF23) is a phosphatonin that is secreted by osteocytes and osteoblasts in response to hyperphosphatemia and 1,25-dihydroxyvitamin D (1,25D). It acts on its receptor complex, Klotho-FGFR1c (fibroblast growth factor receptor 1 c-splicing form), in the distal convoluted tubule to repress renal phosphorus reabsorption in the proximal tubule and suppress the renal synthesis of 1,25D. Klotho-FGFR1c is also expressed in the parathyroid glands. FGF23 acts on the receptor complex in the parathyroid glands to decrease parathyroid hormone (PTH) gene expression and PTH secretion through activation of the MAPK pathway. In chronic kidney disease (CKD), both FGF23 and PTH are increased, implying resistance of the parathyroid glands to FGF23. There is a decrease in the Klotho-FGFR1c complex in the parathyroid glands in both experimental CKD and in patients with end-stage renal disease. In addition, in advanced experimental CKD, FGF23 has a decreased ability to inhibit PTH expression.

  18. MRI of mediastinal parathyroid cystic adenoma causing hyperparathyroidism

    SciTech Connect

    Soler, R.; Bargiela, A.; Cordido, F.; Aguilera, C.; Argueeso, R.; Cao, I.

    1996-01-01

    Primary hyperparathyroidism is a common disorder that results from an increased secretion of parathyroid hormone, most often due to a solitary and solid parathyroid adenoma usually found in the inferior group of parathyroid glands. Parathyroid gland is ectopic in approximately 10 to 20% of the cases, and the retrosternal and prevascular mediastinum is the most common location. Most mediastinal parathyroid adenomas are solid and <3 cm, but mediastinal parathyroid cysts are very uncommon and rarely cause hyperparathyroidism. We know of 18 cases of mediastinal parathyroid cysts that have been previously reported and only four of them presented with hyperparathyroidism. We report an unusual case of hyperparathyroidism due to a large cystic parathyroid adenoma located in the anterior mediastinum diagnosed by MRI. 2 refs., 1 fig.

  19. Parathyroid Hormone, Calcitonin, and Vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T.

    1972-01-01

    Analyses of secretion of parathyroid hormone during tests of stimulation and suppression of hormone-secretory activity using infusions of EDTA and calcium, respectively, have established that, in contrast to previous views, secretion of the hormone is not autonomous in many patients that have adenomatous hyperparathyroidism, but is responsive to changes in blood-calcium concentration. These findings have led to a new understanding of the pathophysiology of hormone production in hyperparathy-roidism. A related application of the diagnostic use of the radioimmunoassay is the preoperative localization of parathyroid tumors and the distinction between adenomas and chief-cell hyperplasia. Work involving catheterization and radioimmunoassay of blood samples obtained from the subclavin and innominate veins and the venae cavae, led to localization in a high percentage of patients. However, this procedure has been adopted recently to detect hormone concentration in the small veins directly draining the parathyroid glands.

  20. Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis

    PubMed Central

    Kamali, D; Sharpe, A; Nagarajan, S; Elsaify, W

    2016-01-01

    Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having ‘something stuck in my throat’. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy. PMID:27055408

  1. Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid cells

    SciTech Connect

    Mizobuchi, Masahide; Ogata, Hiroaki Hatamura, Ikuji; Saji, Fumie; Koiwa, Fumihiko; Kinugasa, Eriko; Koshikawa, Shozo; Akizawa, Tadao

    2007-10-12

    Calcimimetic compounds inhibit not only parathyroid hormone (PTH) synthesis and secretion, but also parathyroid cell proliferation. The aim of this investigation is to examine the effect of the calcimimetic compound NPS R-568 (R-568) on parathyroid cell death in uremic rats. Hyperplastic parathyroid glands were obtained from uremic rats (subtotal nephrectomy and high-phosphorus diet), and incubated in the media only or the media which contained high concentration of R-568 (10{sup -4} M), or 10% cyclodextrin, for 6 h. R-568 treatment significantly suppressed medium PTH concentration compared with that of the other two groups. R-568 treatment not only increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay-positive cells, but also induced the morphologic changes of cell death determined by light or electron microscopy. These results suggest that CaR activation by R-568 accelerates parathyroid cell death, probably through an apoptotic mechanism in uremic rats in vitro.

  2. Protean Presentations of Parathyroid Adenoma in Childhood

    PubMed Central

    Dey, Subrata; Beawarwala, Aziz; Gupta, Saikat

    2017-01-01

    Parathyroid adenoma is a rare disease which is known to present with protean manifestations, leading to misdiagnosis in the initial stage of the disease. It is known to pose a diagnostic dilemma to the clinician, in which a high index of suspicion alone often leads to a proper diagnosis and timely management. We encountered two such cases who presented to us with varied presentation, in which nuclear scintigraphy along with intraoperative parathyroid hormone assay played a major role in diagnosis and management. PMID:28082776

  3. Imaging of the parathyroid glands in primary hyperparathyroidism.

    PubMed

    Minisola, Salvatore; Cipriani, Cristiana; Diacinti, Daniele; Tartaglia, Francesco; Scillitani, Alfredo; Pepe, Jessica; Scott-Coombes, David

    2016-01-01

    Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases worldwide. Surgery is the only potentially curable option for patients with this disorder, even though in asymptomatic patients 50 years of age or older without end organ complications, a conservative treatment may be a possible alternative. Bilateral neck exploration under general anaesthesia has been the standard for the definitive treatment. However, significant improvements in preoperative imaging, together with the implementation of rapid parathyroid hormone determination, have determined an increased implementation of focused, minimally invasive surgical approach. Surgeons prefer to have a localization study before an operation (both in the classical scenario and in the minimally invasive procedure). They are not satisfied by having been referred a patient with just a biochemical diagnosis of PHPT. Imaging studies must not be utilized to make the diagnosis of PHPT. They should be obtained to both assist in determining disease etiology and to guide operative procedures together with the nuclear medicine doctor and, most importantly, with the surgeon. On the contrary, apart from minimally invasive procedures in which localization procedures are an obligate choice, some surgeons believe that literature on parathyroidectomy over the past two decades reveals a bias towards localization. Therefore, surgical expertise is more important than the search for abnormal parathyroid glands.

  4. Ultrasonographic evaluation of parathyroid hyperplasia in multiple endocrine neoplasia type 1: Positive correlation between parathyroid volume and circulating parathyroid hormone concentration.

    PubMed

    Tamiya, Hiroyuki; Miyakawa, Megumi; Takeshita, Akira; Miura, Daishu; Takeuchi, Yasuhiro

    2015-09-01

    There are few reports on parathyroid ultrasonography of multiple endocrine neoplasia type 1 (MEN1). This study investigated the ultrasonographic features of parathyroid glands in 10 patients with MEN1 who underwent preoperative neck ultrasonography and parathyroidectomy between 2006 and 2010 at Toranomon Hospital. We retrospectively analyzed clinical features, laboratory and ultrasonographic data, and pathological diagnosis. A total of 38 parathyroid glands were surgically removed (three to five glands from each patient). All removed parathyroids were pathologically diagnosed as hyperplasia. Seven cases (70.0 %) had adenomatous thyroid nodules. Twenty-five enlarged parathyroid glands (65.8 %) were detected by preoperative ultrasonography with a detection rate of 81.8 % (9/11) and 59.3 % (16/27) for patients without and with adenomatous nodules, respectively. Total parathyroid gland weight and potentially predictable total parathyroid volume by preoperative ultrasonography were significantly correlated with preoperative serum intact parathyroid hormone (iPTH) concentration (R = 0.97, P < 0.001 and R = 0.96, P < 0.001, respectively). The equation used for prediction of the total volume by ultrasonography was 15 × iPTH (pg/ml) - 1,000 and that for total weight was 20 × iPTH (pg/ml) - 1,400. Although adenomatous nodules often coexisted with MEN1 and made identification of enlarged parathyroid glands by ultrasonography difficult, the positive correlation between the predictable parathyroid volume by ultrasonography and serum iPTH suggests that their measurement is useful in the preoperative detection and localization of enlarged parathyroid glands in patients with MEN1. Furthermore, the presence of parathyroid glands that should be resected can be predicted before surgery using the equation proposed here.

  5. In experimental chronic kidney disease or cancer, parathyroid hormone is a novel mediator of cachexia.

    PubMed

    Wyatt, Christina M; Mitch, William E

    2016-05-01

    Hyperparathyroidism plays a central role in the disordered bone mineral metabolism of chronic kidney disease, and has been associated with increased cardiovascular morbidity and mortality in that setting. A recent study suggests a novel role for parathyroid hormone and its receptor in muscle wasting and cachexia occurring in advanced chronic kidney disease.

  6. Absence of RET proto-oncogene point mutations in sporadic hyperplastic and neoplastic lesions of the parathyroid gland.

    PubMed Central

    Padberg, B. C.; Schröder, S.; Jochum, W.; Kastendieck, H.; Roth, J.; Heitz, P. U.; Komminoth, P.

    1995-01-01

    We investigated the possible role of RET proto-oncogene mutations in the development of sporadic hyperplastic, benign, and malignant parathyroid lesions. DNA extracted from paraffin-embedded specimens of forty parathyroid lesions was screened for RET proto-oncogene point mutations in exons 10, 11, and 16 by nonisotopic polymerase chain reaction-based single-strand conformation polymorphism and heteroduplex gel electrophoresis. The nucleotide sequence of samples with aberrant band patterns was identified by nonisotopic direct sequencing of polymerase chain reaction-amplified DNA. Parathyroids of seven patients with multiple endocrine neoplasia type 2A (MEN 2A) and MEN 2B served as positive controls. None of the eight hyperplastic lesions, three cases of parathyromatosis, ten parathyroid adenomas, eleven carcinomas or one normal parathyroid gland contained mutations in each of the three RET exons tested. Six MEN-2A-associated hyperplastic glands exhibited identical band shifts in the polymerase chain reaction single-strand conformation polymorphism analysis of exon 11, which corresponded to a Cys 634-->Arg substitution in the nucleotide sequence analysis (TGC-->CGC), whereas in the MEN 2B parathyroid specimen a point mutation was found at codon 918 of exon 16 (ATG-->ACG), causing a Met 918-->Thr substitution. Our data indicate that RET mutations of the MEN 2 loci in exons 10, 11, and 16 are not involved in the development of sporadically occurring benign or malignant parathyroid lesions. Furthermore, our results are in accordance with the observation that MEN 2A patients with Cys 634-->Arg (germline) mutations have a higher risk of developing parathyroid disease than those with other mutations at codon 634. Images Figure 1 Figure 2 PMID:7495285

  7. EGFR Activation Increases Parathyroid Hyperplasia and Calcitriol Resistance in Kidney Disease

    PubMed Central

    Arcidiacono, Maria Vittoria; Sato, Tetsuhiko; Alvarez-Hernandez, Daniel; Yang, Jing; Tokumoto, Masanori; Gonzalez-Suarez, Ignacio; Lu, Yan; Tominaga, Yoshihiro; Cannata-Andia, Jorge; Slatopolsky, Eduardo; Dusso, Adriana S.

    2008-01-01

    Calcitriol, acting through vitamin D receptors (VDR) in the parathyroid, suppresses parathyroid hormone synthesis and cell proliferation. In secondary hyperparathyroidism (SH), VDR content is reduced as hyperplasia becomes more severe, limiting the efficacy of calcitriol. In a rat model of SH, activation of the EGF receptor (EGFR) by TGF-α is required for the development of parathyroid hyperplasia, but the relationship between EGFR activation and reduced VDR content is unknown. With the use of the same rat model, it was found that pharmacologic inhibition of EGFR activation with erlotinib prevented the upregulation of parathyroid TGF-α, the progression of growth, and the reduction of VDR. Increased TGF-α/EGFR activation induced the synthesis of liver-enriched inhibitory protein, a potent mitogen and the dominant negative isoform of the transcription factor CCAAT enhancer binding protein-β, in human hyperplastic parathyroid glands and in the human epidermoid carcinoma cell line A431, which mimics hyperplastic parathyroid cells. Increases in liver-enriched inhibitory protein directly correlated with proliferating activity and, in A431 cells, reduced VDR expression by antagonizing CCAAT enhancer binding protein-β transactivation of the VDR gene. Similarly, in nodular hyperplasia, which is the most severe form of SH and the most resistant to calcitriol therapy, higher TGF-α activation of the EGFR was associated with an 80% reduction in VDR mRNA levels. Thus, in SH, EGFR activation is the cause of both hyperplastic growth and VDR reduction and therefore influences the efficacy of therapy with calcitriol. PMID:18216322

  8. Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism

    PubMed Central

    Ribeiro, Cláudia; Penido, Maria Goretti Moreira Guimarães; Guimarães, Milena Maria Moreira; Tavares, Marcelo de Sousa; Souza, Bruno das Neves; Leite, Anderson Ferreira; de Deus, Leonardo Martins Caldeira; Machado, Lucas José de Campos

    2016-01-01

    AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure. METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics (etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory (calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables. RESULTS Fifty-three patients (66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product (P = 0.03 and P = 0.006, respectively). They also had lower mortality (32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events (27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg2/dL2 [RR 1.48 (1.06, 2.08), P = 0.03], presence of vascular calcification [1.33 (1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25 (1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality. CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure. PMID:27648407

  9. Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors.

    PubMed

    Mingione, Alessandra; Verdelli, Chiara; Terranegra, Annalisa; Soldati, Laura; Corbetta, Sabrina

    2015-01-01

    Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors.

  10. Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration

    PubMed Central

    Rodríguez-Ortiz, Maria E.; Canalejo, Antonio; Herencia, Carmen; Martínez-Moreno, Julio M.; Peralta-Ramírez, Alan; Perez-Martinez, Pablo; Navarro-González, Juan F.; Rodríguez, Mariano; Peter, Mirjam; Gundlach, Kristina; Steppan, Sonja; Passlick-Deetjen, Jutta; Muñoz-Castañeda, Juan R.; Almaden, Yolanda

    2014-01-01

    Background The interest on magnesium (Mg) has grown since clinical studies have shown the efficacy of Mg-containing phosphate binders. However, some concern has arisen for the potential effect of increased serum Mg on parathyroid hormone (PTH) secretion. Our objective was to evaluate the direct effect of Mg in the regulation of the parathyroid function; specifically, PTH secretion and the expression of parathyroid cell receptors: CaR, the vitamin D receptor (VDR) and FGFR1/Klotho. Methods The work was performed in vitro by incubating intact rat parathyroid glands in different calcium (Ca) and Mg concentrations. Results Increasing Mg concentrations from 0.5 to 2 mM produced a left shift of PTH–Ca curves. With Mg 5 mM, the secretory response was practically abolished. Mg was able to reduce PTH only if parathyroid glands were exposed to moderately low Ca concentrations; with normal–high Ca concentrations, the effect of Mg on PTH inhibition was minor or absent. After 6-h incubation at a Ca concentration of 1.0 mM, the expression of parathyroid CaR, VDR, FGFR1 and Klotho (at mRNA and protein levels) was increased with a Mg concentration of 2.0 when compared with 0.5 mM. Conclusions Mg reduces PTH secretion mainly when a moderate low calcium concentration is present; Mg also modulates parathyroid glands function through upregulation of the key cellular receptors CaR, VDR and FGF23/Klotho system. PMID:24103811

  11. THE ANTAGONISM BETWEEN THYROID AND PARATHYROID GLANDS

    PubMed Central

    Uhlenhuth, Eduard

    1918-01-01

    From the facts stated in this paper it is evident that the thymus gland of mammals contains a substance which is capable of producing tetany when fed to the larvæ of certain species of salamanders (Ambystoma opacum and Ambystoma maculatum). As long as the larvæ have not developed their own thymus glands, they are able, by means of some mechanism, to counterbalance the tetanic action of the thymus substance introduced in their food. When, however, the secretion from their own thymus glands is added to the thymus material introduced with the food, this mechanism of preventing tetany becomes inadequate and tetany ensues. In the larva of a third species of salamander, Ambystoma tigrinum, this mechanism will prevent tetany even when the larvæ are fed on thymus. In mammals the parathyroids are known to prevent tetany and are supposed either to absorb the tetany-producing substance and thus prevent its action or to change it into another non-toxic substance. It is at least probable that in the amphibians the parathyroids play the same rôle. Larvæ of anuran amphibians, which develop their parathyroids soon after hatching, never show tetanic convulsions if they are fed on thymus, but in certain species of salamanders, whose parathyroids develop only during metamorphosis, the larvæ invariably have tetanic convulsions upon thymus feeding, while the metamorphosed animals never show tetany. But in addition to the parathyroids the salamanders must possess still another mechanism which during the larval period inhibits the production of tetany by the animal's own thymus glands. In the larvæ of Ambystoma opacum and Ambystoma maculatum this mechanism is sufficient only to prevent tetany from the animal's own thymus, while in the larvæ of Ambystoma tigrinum it is capable of preventing tetany even when the larvæ are fed with thymus. If the thymus is the organ by whose action tetany is produced, we can understand why tetany in human beings occurs far more frequently in

  12. Clinicopathological phenotype of parathyroid carcinoma: therapeutic and prognostic aftermaths.

    PubMed

    Diaconescu, M R; Glod, M; Costea, I; Grigorovici, M; Diaconescu, S

    2015-01-01

    Parathyroid carcinomas (PC) are rare and "devastating"€ causes of hyperparathyroidism (HP), frequently discovered fortuitously,with not always doubtless pathological confirmation, and dissociate post-therapeutic outcomes and prognosis even after well-performed surgery. We herein report four PT neoplasms,three of them proving to be authentic PCs, and one an atypical parathyroid adenoma. There were three females and one male, aged 32-49 (mean 44) years. In three circumstances PC was associated with primary HP and in one case the tumor had developed on a CKD-BMD (renal HP) background. All patients presented marked clinical and biochemical phenomena related to hypercalcemia with greater intensity of renal, bone, neuromuscular and psychological signs and symptoms to which in one observation specific uremic manifestations were added. Preoperative and intraoperative diagnosis was suspected only in two cases (one of them being in fact an atypical PT adenoma), but in the other two it was established by paraffin section on histological evidence of definitive stigma of malignancy. Our little experience underlines the wide and protean range of the origins, clinical aspects, course and prognosis of PC, which adds to the difficulties of pre- and intraoperative diagnosis. Awareness of this lesion must be permanent to detect its presence in any unusual eventuality, imposing a radical en bloc resection at the initial operation, assuring the best chance of cure.

  13. A case report of mediastinal ectopic parathyroid adenoma presented as parathyroid crisis localized by SPECT/CT

    PubMed Central

    Zhou, Weibin; Chen, Min

    2016-01-01

    Abstract Introduction: Parathyroid crisis due to ectopic parathyroid adenomas can pose diagnostic and management challenges, since it is quite rare in clinical practice. Clinical Findings/Patient Concerns: A 67-year-old Chinese male presented as a parathyroid crisis due to an ectopic mediastinal parathyroid adenoma with his serum calcium and PTH markedly increased in short time. An ultrasonography and computed tomography (CT) scan of the neck did not reveal any parathyroid adenoma. Thoracic CT detected a contrast-enhanced mass in the mediastinum. Although the ectopic location is difficult to appreciate on anterior planar technetium-99m-sestamibi scintigraphy views but has been accurately localized with single photon-emission computed tomography/computed tomography. After fluid resuscitation, loop diuretic, and calcitonin treatment, a thoracoscope surgery was performed. The histopathology of the mediastinal nodule was consistent with a parathyroid adenoma. Hypocalcemia due to hungry bone syndrome occurred after surgery and was resolved quickly with large-dose calcium and calcitriol supplementation. He is asymptomatic and has normal serum calcium and PTH levels on regular follow-up. Diagnoses: The ultrasonography, CT, sestamibi, and single photon-emission computed tomography/computed tomography provide limited sensitivity in the detecting ectopic parathyroid adenomas alone. The combination of these techniques has incremental value in localizing ectopic parathyroid adenomas over either technique alone. Conclusion: Any parathyroid crisis without parathyroid adenoma in the neck should alert physicians to search for ectopic locations through combination of imaging techniques. PMID:27741147

  14. Cervical SPECT Camera for Parathyroid Imaging

    SciTech Connect

    None, None

    2012-08-31

    Primary hyperparathyroidism characterized by one or more enlarged parathyroid glands has become one of the most common endocrine diseases in the world affecting about 1 per 1000 in the United States. Standard treatment is highly invasive exploratory neck surgery called Parathyroidectomy. The surgery has a notable mortality rate because of the close proximity to vital structures. The move to minimally invasive parathyroidectomy is hampered by the lack of high resolution pre-surgical imaging techniques that can accurately localize the parathyroid with respect to surrounding structures. We propose to develop a dedicated ultra-high resolution (~ 1 mm) and high sensitivity (10x conventional camera) cervical scintigraphic imaging device. It will be based on a multiple pinhole-camera SPECT system comprising a novel solid state CZT detector that offers the required performance. The overall system will be configured to fit around the neck and comfortably image a patient.

  15. Proliferative Lesions of Parathyroid Glands: An Update for Practicing Pathologists.

    PubMed

    Shakeel, Shaheera; Mubarak, Muhammed

    2016-01-01

    Pathological lesions of parathyroid glands encompass a wide range of lesions ranging from developmental anomalies to inflammatory disorders to neoplastic processes. Proliferative lesions of parathyroid glands represent the commonest causes of hyperparathyroidism in clinical practice. However, the parathyroid specimens represent only a tiny fraction of the workload received in a non-specialist histopathology laboratory. As a result, the familiarity of the pathologists with the spectrum of parathyroid lesions is generally limited. An accurate diagnosis of the parathyroid lesions is challenging and a daunting task for both the clinicians and the pathologists. The traditional morphological approaches have limitations. Ancillary techniques of immunohistochemistry and molecular biology are being increasingly employed to resolve the diagnostic dilemmas. This review briefly describes the proliferative pathological lesions affecting the parathyroid glands and provides some useful tips on accurately diagnosing these lesions.

  16. [Regulation of bone mineralization by parathyroid hormone].

    PubMed

    Shimizu, Masaru; Tamura, Tatsuya

    2004-06-01

    In randomized clinical trials, parathyroid hormone (PTH) showed potent anabolic effects on the lumbar spine and decreased the risk of incident vertebral fractures dramatically. Although the anabolic effect of PTH on cortical bone in the femoral neck is still unclear, it should be demonstrated in further clinical studies. Concurrent or sequential therapies of PTH and anti-resorptive agents will be one of the major issues of treatment for osteoporosis in the future.

  17. Parathyroid hormone, calcium, and sodium bridging between osteoporosis and hypertension in postmenopausal Korean women.

    PubMed

    Park, Jee Soo; Choi, Soo Beom; Rhee, Yumie; Chung, Jai Won; Choi, Eui-Young; Kim, Deok Won

    2015-05-01

    The coexistence of osteoporosis and hypertension, which are considered distinct diseases, has been widely reported. In addition, daily intake of calcium and sodium, as well as parathyroid hormone levels (PTH), is known to be associated with osteoporosis and hypertension. This study aimed to determine the association of low calcium intake, high sodium intake, and PTH levels with osteoporosis and hypertension in postmenopausal Korean women. Data for postmenopausal Korean women aged 50 years or older were obtained from the Korea National Health and Nutrition Examination Survey 2008-2011. Osteoporosis was diagnosed using dual energy X-ray absorptiometry, while hypertension was diagnosed using blood pressure data. The odds ratios for osteoporosis and hypertension were calculated using logistic regression analysis for quartiles of the daily calcium intake, daily sodium intake, and PTH levels. Women with hypertension had a high coexistence of osteoporosis (43.6 vs. 36.5 %; P = 0.022), and vice versa (21.1 vs. 16.6 %; P = 0.022). PTH was significantly associated with osteoporosis and hypertension, and a high intake of calcium was strongly correlated with a low incidence of osteoporosis. This is the first study to report the characteristics of postmenopausal Korean women who have high dietary sodium intake and low dietary calcium intake, in association with the incidence of osteoporosis and hypertension. Osteoporosis and hypertension were strongly associated with each other, and PTH appears to be a key mediator of both diseases, suggesting a possible pathogenic link.

  18. Seminoma and parathyroid adenoma in a snow leopard (Panthera unica).

    PubMed

    Doster, A R; Armstrong, D L; Bargar, T W

    1989-05-01

    A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline.

  19. Multimodality imaging of the thyroid and parathyroid glands

    SciTech Connect

    Sandler, M.P.; Patton, J.A.

    1987-01-01

    Nuclear imaging of the thyroid and parathyroid glands has evolved from early radionuclide rectilinear thyroid scanning to the recently developed dual isotope subtraction technique for detecting parathyroid lesions. At the same time, x-ray fluorescent scanning, ultrasound, x-ray computed tomography, and magnetic resonance imaging have improved identification of these endocrine organs. The appropriate use and relative role of these imaging modalities in the investigation of patients with thyroid and parathyroid diseases is discussed.

  20. Identification of parathyroid glands: anatomical study and surgical implications.

    PubMed

    Melo, Catarina; Pinheiro, Susana; Carvalho, Lina; Bernardes, António

    2015-03-01

    While performing thyroid surgery, the unintentional lesion of parathyroid glands and laryngeal nerves results in a profound alteration in patient's quality of life. To minimize thyroid surgery morbidity, the surgeon must have an in-depth knowledge of the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck. This work intended to simulate total thyroidectomies using cadaver parts and isolate fragments that may correspond to parathyroid glands. The thyroid glands and "eventual" parathyroid glands were then submitted to histological study. Ninety-two cadaver parts were used for macroscopic dissection. A total of 242 fragments were isolated, 154 of which were confirmed through histological study to be parathyroid glands. In 36 cases, all "eventual" parathyroid glands isolated during dissection were confirmed through histological verification. In 40 cases, some glands were confirmed. In 16 cases, none of the "eventual" parathyroid glands was confirmed. The 92 thyroid glands isolated during dissection were also submitted to histological study. In 21 thyroid glands, 16 parathyroid glands were identified in the histological cuts: 8 sub-capsular, 8 extra-capsular, 6 intra-thyroidal. There was no statistical difference between the dimensions of the parathyroid glands. Parathyroid gland identification and preservation are sometimes a challenge during thyroid surgery, difficulty that has been demonstrated during dissection of cadaver parts.

  1. FGF23 fails to inhibit uremic parathyroid glands.

    PubMed

    Canalejo, Rocío; Canalejo, Antonio; Martinez-Moreno, Julio Manuel; Rodriguez-Ortiz, M Encarnacion; Estepa, Jose C; Mendoza, Francisco Javier; Munoz-Castaneda, Juan Rafael; Shalhoub, Victoria; Almaden, Yolanda; Rodriguez, Mariano

    2010-07-01

    Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D(3). FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal-regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signal-regulated kinase 1/2-mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition.

  2. Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor

    SciTech Connect

    McKinstry, William J.; Polekhina, Galina; Diefenbach-Jagger, Hannelore; Ho, Patricia W.M.; Sato, Koh; Onuma, Etsuro; Gillespie, Matthew T.; Martin, T. John; Parker, Michael W.

    2009-08-18

    Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have determined the crystal structure of the complex between PTHrP (residues 1-108) and a neutralizing monoclonal anti-PTHrP antibody that reveals the only point of contact is an {alpha}-helical structure extending from residues 14-29. Another striking feature is that the same residues that interact with the antibody also interact with parathyroid hormone receptor 1, showing that the antibody and the receptor binding site on the hormone closely overlap. The structure explains how the antibody discriminates between the two hormones and provides information that could be used in the development of novel agonists and antagonists of their common receptor.

  3. Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors.

    PubMed

    Mingione, Alessandra; Verdelli, Chiara; Ferrero, Stefano; Vaira, Valentina; Guarnieri, Vito; Scillitani, Alfredo; Vicentini, Leonardo; Balza, Gianni; Beretta, Edoardo; Terranegra, Annalisa; Vezzoli, Giuseppe; Soldati, Laura; Corbetta, Sabrina

    2017-02-01

    Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca(2+)]o). [Ca(2+)]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca(2+)]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.

  4. Parathyroid carcinoma masquerading as morning sickness in pregnancy.

    PubMed

    Panchani, Roopal; Varma, Tarun; Goyal, Ashutosh; Tripathi, Sudhir

    2013-10-01

    Incidence of primary hyperparathyroidism (PHP) in pregnancy is 8/100,000 population/year with less than 200 cases reported. Physiological changes associated with pregnancy make a diagnosis of PHP difficult and 80% are asymptomatic. High index of suspicion is required as physiological hypocalcemia related to hemodilution, increased glomerular filtration rate resulting in maternal hypercalciuria and gestational hypoalbuminemia can mask hypercalcemia of PHP. Maternal and fetal complication rates are high. Early recognition followed by appropriate management and treatment significantly reduces complications. Here, we present a rare case of parathyroid carcinoma in pregnancy and highlight the difficulties in diagnosis given the non-specific symptoms related to hypercalcemia. We have also discussed the management of PHP during the pregnancy. PHP is a preventable cause of fetal and maternal morbidity and mortality.

  5. Influence of parathyroid hormone on bone cell ultrastructure

    SciTech Connect

    Matthews, J.L.; Talmage, R.V.

    1981-05-01

    A study in rats demonstrated that morphologic changes in the bone osteocytes and osteoblasts are produced following parathyroid hormone (PTH) injection into thyroparathyroidectomized animals. It further showed that similar changes occur in normal rats as the result of extended fasting. The most significant morphologic alterations involved surface microvilli and blebs as determined by scanning electron microscopy. Transmission electron microscopy studies showed alterations in the cisternae of the rough endoplasmic reticulum. Additionally, cell shape varied markedly from the control cuboidal morphology. These morphologic changes occurred during peak periods of plasma calcium change and returned to control morphology as plasma calcium levels normalized. The study supports the concept that osteocytes and lining cells on the surface of bone play a role in maintenance of plasma calcium concentrations. (JMT)

  6. Proliferation of endothelial component of parathyroid gland in multiple endocrine neoplasia type 1. Potential relationship with a mitogenic factor.

    PubMed Central

    D'Adda, T.; Amorosi, A.; Bussolati, G.; Brandi, M. L.; Bordi, C.

    1993-01-01

    The basic fibroblast growth factor-like mitogen detected in the plasma of patients with the multiple endocrine neoplasia type 1 (MEN-1) syndrome was found to have a specific mitogenic effect on parathyroid endothelial cells in vitro. To investigate its pathogenic role in humans, the endothelial component of parathyroid glands was evaluated by ultrastructural morphometry in six MEN-1 patients. The results were compared with those found in six patients with uremic hyperparathyroidism (UHPT) and in three subjects with histologically normal glands. Plasma mitogenic activity was found in all MEN-1 patients but not in those with UHPT or in normal subjects. All morphometric parameters investigated (fractional volume and nuclear density of capillary endothelial cells, volume fraction and number per unit area of capillaries) showed 1.5- to 2-fold higher values in patients with MEN-1 than in those with UHPT (P < 0.05). In contrast, no difference was found between MEN-1 cases and normal subjects. Quantitative evaluation of parathyroid pericytes yielded results similar to those of endothelial cells. These data indicate that the proliferation of parathyroid cells in MEN-1 patients is accompanied by parallel increase in the associated endothelial component that does not occur in patients with UHPT and may support the hypothesis of an in vivo role of the MEN-1 mitogen factor on the endothelial component of parathyroid glands in MEN-1 patients. Images Figure 1 PMID:8102033

  7. High-performance liquid chromatographic methods for the analysis of human parathyroid hormone in reference standards, parathyroid tissue and biological fluids.

    PubMed

    Zanelli, J M; Kent, J C; Rafferty, B; Nissenson, R A; Nice, E C; Capp, M W; O'Hare, M J

    1983-08-12

    Reversed-phase high-performance liquid chromatography (RP-HPLC) has been used to fractionate human parathyroid hormone (hPTH) from a variety of natural sources and to compare it with synthetic hPTH and hPTH fragments. Multiple radioimmunoassay systems for amino, mid and carboxyl regions of hPTH were used to monitor various preparations of hPTH previously prepared by conventional methods and ampouled in nanogram amounts for reference standard and reagent purposes. Results confirmed that they were free of detectable cleavage products, but showed that the intact hPTH comprised three or four closely associated components. A similar pattern of heterogeneity was obtained when hPTH was extracted from stored human parathyroid adenomata by a simple rapid HPLC bulk fractionation method. Comparison with synthetic 1-84 hPTH and modification of sample handling to minimize oxidative conditions, indicate that some of these components are probably intermediate oxidation products. A number of less hydrophobic components, with carboxyl region immunoreactivities, were obtained from the individual adenoma samples, human parathyroid cyst fluid, ampouled samples of human adenoma tissue culture medium, and secondary hyperparathyroid plasma ultrafiltrate when they were fractionated by RP-HPLC. The results strongly suggest that the biological degradation of hPTH is more complex than generally believed, and that RP-HPLC offers a new dimension in its analysis.

  8. Oxyphil Cell Parathyroid Adenomas Causing Primary Hyperparathyroidism: a Clinico-Pathological Correlation.

    PubMed

    Howson, Pamela; Kruijff, Schelto; Aniss, Ahmad; Pennington, Thomas; Gill, Anthony J; Dodds, Tristan; Delbridge, Leigh W; Sidhu, Stan B; Sywak, Mark S

    2015-09-01

    Oxyphil cell parathyroid adenomas (OPA) are considered to be an uncommon cause of primary hyperparathyroidism (PHPT), and were historically thought to be clinically silent. It has been our clinical impression that these adenomas present more often than previously thought and may manifest a more severe form of primary hyperparathyroidism than classical adenoma. The aim of this study was to describe the incidence and clinical presentation of OPA. An observational case-control study was undertaken. The study group comprised patients undergoing parathyroidectomy for PHPT where the final pathology confirmed OPA. The controls were made up of an age- and sex-matched group of patients having parathyroidectomy in the same time period where the final pathology confirmed a classical or non-oxyphil adenoma. OPA were defined as parathyroid tumours containing >75% oxyphilic cells. The OPA cases were obtained by reviewing all histopathology slides over an 11-year period (2002-12) where the reports contained the words 'oxyphil' or 'oxyphilic' parathyroid adenomas. These were then reviewed by two independent pathologists to confirm a diagnosis of OPA. The primary outcome measures were preoperative serum calcium and parathyroid hormone (PTH) levels. Secondary outcome measures were symptoms at presentation, accuracy of preoperative localization studies, parathyroid gland weight following surgery, and type of surgery undertaken. In the period 2002-2012, 2739 patients underwent surgery for PHPT. Following pathological review, 91 cases were confirmed as being OPA and formed the study group. A control group (n = 91) from the same period was selected following matching on the basis of age at presentation and sex. OPA were associated with higher preoperative serum calcium (10.84 versus 10.48 mg/dL, p < 0.001) and parathyroid hormone (139 versus 64 ng/L, p < 0.001). At presentation, a lower proportion of OPA cases had asymptomatic disease (15 versus 29%, p = 0.03). There was

  9. Full length parathyroid hormone (1–84) in the treatment of osteoporosis in postmenopausal women

    PubMed Central

    Jódar-Gimeno, Esteban

    2007-01-01

    Objective: To review the pharmacological properties and the available clinical data of full length parathyroid hormone (PTH) in post-menopausal osteoporosis. Sources: A MEDLINE search was completed, together with a review of information obtained from the manufacturer and from the medicine regulatory agencies. Study and data selection: Studies were selected according to relevance and availability. Relevant information (design, objectives, patients’ characteristics, outcomes, adverse events, dosing, etc) was analyzed. Results: Different studies have shown that, when administered intermittently as a subcutaneous injection in the abdomen, PTH increases bone mineral density (BMD) and prevents vertebral fractures. On completion of PTH therapy (up to 24 months), there is evidence that sequential treatment with alendronate is associated with a therapeutic benefit in terms of increase in BMD. Further trials are necessary to determine long-term safety and the role of PTH in combination with other treatments for osteoporosis and the effect of repeated cycles of PTH followed by an anti-catabolic agent. There are currently no completed comparative trials with other osteoporosis treatments. Conclusions: Full length PTH, given intermittently as an abdominal subcutaneous injection, appears to be a safe and efficacious treatment option for high risk osteoporosis. More data are needed to determine its specific role in osteoporosis treatment. PMID:18044089

  10. Huge Parathyroid Adenoma with Dysphagia Presentation; A Case Report from Southern Iran

    PubMed Central

    Ziaeean, Bizhan; Sohrabi-Nazari, Sahar

    2016-01-01

    Parathyroid adenoma is a benign tumor of the parathyroid glands. The cause of most parathyroid adenomas is unknown. Parathyroid adenoma increases the secretion of parathyroid hormone and results in primary hyperparathyroidism. High amounts of parathyroid hormone in the blood cause the imbalance of calcium, which leads to various complications such as kidney stones, depression, lethargy, nausea, vomiting, abdominal pain, myalgia, bone and joint pain, hoarseness, etc. Oropharyngeal dysphagia is defined as having problem in swallowing due to abnormalities in the structure and function of oropharynx and other related organs. The exact prevalence of dysphagia caused by parathyroid adenoma is unknown, but since this complication can lead to increased mortality and morbidity, its diagnosis is important. It is difficult to distinguish parathyroid malignancies from parathyroid adenoma even after surgery. Therefore, the final diagnosis is possible through surgery and histopathological evaluation. Here, a case of parathyroid adenoma with first presentation of generalized weakness and dysphagia has been reported. PMID:27582595

  11. Near-infrared autofluorescence for the detection of parathyroid glands.

    PubMed

    Paras, Constantine; Keller, Matthew; White, Lisa; Phay, John; Mahadevan-Jansen, Anita

    2011-06-01

    A major challenge in endocrine surgery is the intraoperative detection of parathyroid glands during both thyroidectomies and parathyroidectomies. Current localization techniques such as ultrasound and sestamibi scan are mostly preoperative and rely on an abnormal parathyroid for its detection. In this paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real-time, automated in vivo method for the detection of the parathyroid gland. A pilot in vivo study was conducted to assess the ability of NIR fluorescence to identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence measurements at 785 nm excitation were obtained intra-operatively from the different tissues exposed in the neck region in 21 patients undergoing endocrine surgery. The fluorescence intensity of the parathyroid gland was found to be consistently greater than that of the thyroid and all other tissues in the neck of all patients. In particular, parathyroid fluorescence was two to eleven times higher than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm. These results indicate that NIR fluorescence has the potential to be an excellent optical tool to locate parathyroid tissue during surgery.

  12. Near-infrared autofluorescence for the detection of parathyroid glands

    NASA Astrophysics Data System (ADS)

    Paras, Constantine; Keller, Matthew; White, Lisa; Phay, John; Mahadevan-Jansen, Anita

    2011-06-01

    A major challenge in endocrine surgery is the intraoperative detection of parathyroid glands during both thyroidectomies and parathyroidectomies. Current localization techniques such as ultrasound and sestamibi scan are mostly preoperative and rely on an abnormal parathyroid for its detection. In this paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real-time, automated in vivo method for the detection of the parathyroid gland. A pilot in vivo study was conducted to assess the ability of NIR fluorescence to identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence measurements at 785 nm excitation were obtained intra-operatively from the different tissues exposed in the neck region in 21 patients undergoing endocrine surgery. The fluorescence intensity of the parathyroid gland was found to be consistently greater than that of the thyroid and all other tissues in the neck of all patients. In particular, parathyroid fluorescence was two to eleven times higher than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm. These results indicate that NIR fluorescence has the potential to be an excellent optical tool to locate parathyroid tissue during surgery.

  13. Controversies in the management of parathyroid carcinoma: A case series and review of the literature.

    PubMed

    Medas, Fabio; Erdas, Enrico; Loi, Giulia; Podda, Francesco; Pisano, Giuseppe; Nicolosi, Angelo; Calò, Pietro Giorgio

    2016-04-01

    Parathyroid carcinoma is a rare malignancy representing less than 1% of primary hyperparathyroidism cases. Its management is controversial due to lack of large-scale, multicentric studies. We report 8 new cases of parathyroid carcinoma and review the literature. Preoperative diagnosis of carcinoma was possible in 2 (25%) cases. Unclear surgical margins were present in 5 (62.5%) patients; 4 of them underwent subsequent re-exploration and ipsilateral hemithyroidectomy, in one case associated to central lymph node dissection. Recurrent disease is reported in 2 (25%) patients. Considering the high incidence of local recurrence in case of unclear surgical margins, a re-exploration with ipsilateral hemithyroidectomy is indicated in these patients. A neck dissection should be performed only in case of clinically involved lymph nodes, avoiding prophylactic lymphectomy. An aggressive approach is indicated in case of local or distant recurrence to reduce hypercalcemia.

  14. Germline and somatic mutations in cyclin-dependent kinase inhibitor genes CDKN1A, CDKN2B, and CDKN2C in sporadic parathyroid adenomas.

    PubMed

    Costa-Guda, Jessica; Soong, Chen-Pang; Parekh, Vaishali I; Agarwal, Sunita K; Arnold, Andrew

    2013-10-01

    The molecular pathogenesis of sporadic parathyroid adenomas is incompletely understood. The possible role of cyclin-dependent kinase inhibitor (CDKI) genes was raised by recognition of cyclin D1 as a parathyroid oncogene, identification of rare germline mutations in CDKI genes in patients with multiple endocrine neoplasia type 1; that in rodents, mutation in Cdkn1b caused parathyroid tumors; and subsequently through identification of rare predisposing germline sequence variants and somatic mutation of CDKN1B, encoding p27(kip1), in sporadic human parathyroid adenoma. We therefore sought to determine whether mutations/variants in the other six CDKI genes CDKN1A, CDKN1C, CDKN2A, CDKN2B, CDKN2C, and CDKN2D, encoding p21, p57, p14(ARF)/p16, p15, p18, and p19, respectively, contribute to the development of typical parathyroid adenomas. In a series of 85 sporadic parathyroid adenomas, direct DNA sequencing identified alterations in five adenomas (6 %): Two contained distinct heterozygous changes in CDKN1A, one germline and one of undetermined germline status; one had a CDKN2B germline alteration, accompanied by loss of the normal allele in the tumor (LOH); two had variants of CDKN2C, one somatic and one germline with LOH. Abnormalities of three of the mutant proteins were readily demonstrable in vitro. Thus, germline mutations/rare variants in CDKN1A, CDKN2B, and CDKN2C likely contribute to the development of a significant subgroup of common sporadic parathyroid adenomas, and somatic mutation in CDKN2C further suggests a direct role for CDKI alteration in conferring a selective growth advantage to parathyroid cells, providing novel support for the concept that multiple CDKIs can play primary roles in human neoplasia.

  15. Estimation of parenchymal cell content of human parathyroid glands using the image analyzing computer technique.

    PubMed Central

    Grimelius, L.; Akerström, G.; Johansson, H.; Lundqvist, H.

    1978-01-01

    By means of the image analyzing computer technique, a complete determination of the parenchymal tissue distribution in serially sectioned parathyroid glands were accomplished. The technique had good reproducibility. Taking into account the shrinkage of the different tissue components during histotechnical procedures and the tissue densities, it was possible to calculate the parenchymal cell mass of unfixed glands. The cell distribution varied considerably, and in most glands as many as 10 sections at different levels had to be examined to get a reliable ratio between the parenchymal and fat cell tissue. The results seriously question the validity of histopathologic examination of one or a few sections of parathyroid glands in evaluation of the parenchymal cell mass, as well as diagnoses based on examination of partial glandular biopsy specimens. PMID:717545

  16. The history of the parathyroid surgery.

    PubMed

    Toneto, Marcelo Garcia; Prill, Shandi; Debon, Leticia Manoel; Furlan, Fernando Zucuni; Steffen, Nedio

    2016-01-01

    The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment. RESUMO Os autores fizeram uma revisão dos principais aspectos históricos da progressão do conhecimento sobre o tratamento cirúrgico do hiperparatireoidismo. Por meio de revisão bibliográfica, foram analisados artigos selecionados sobre a história da evolução do conhecimento anatômico, fisiológico, patológico e cirúrgico das glândulas paratireoides. Devido às suas características anatômicas peculiares, as paratireoides foram as últimas das glândulas endócrinas a serem descobertas, o que dificultou sobremaneira seu tratamento adequado até as primeiras décadas do Século XX. A evolução tecnológica ocorrida nos últimos 30 anos facilitou sobremaneira a localização das glândulas e a cirurgia do hiperparatireoidismo. Contudo, um cirurgião experiente e dedicado ao tratamento dessa enfermidade ainda é fundamental para a excelência do tratamento.

  17. Compression of the trachea by a mediastinal parathyroid cyst.

    PubMed

    Hauet, E J; Paul, M A; Salu, M K

    1997-09-01

    Parathyroid cysts are a rare cause of space-occupying lesions in the mediastinum. Because symptoms are not specific, the diagnosis is seldom made before operation. Removal was done through a cervical incision without sternal splitting.

  18. [Ectopic parathyroid glands. Imaging methods and surgical access].

    PubMed

    Fialová, M; Adámková, J; Adámek, S; Libánský, P; Kubinyi, J

    2014-08-01

    We discuss the benefits of imaging methods in localizing ectopic parathyroid glands in patients with primary hyperparathyroidism. The ectopic localizations are discussed within the context of the orthotopic norm. In the sample of 123 patients, a 23% rate of ectopic parathyroid glands was detected. Three selected case studies are presented, supporting the benefit of SPECT/CT imaging in terms of surgical access strategy selection.

  19. Persistent renal hyperparathyroidism caused by intrathyroidal parathyroid glands.

    PubMed

    Chen, Chin-Li; Lin, Shih-Hua; Yu, Jyh-Cherng; Shih, Ming-Lang

    2014-09-01

    Renal hyperparathyroidism usually occurs in chronic renal failure patients on regular dialysis. However, renal hyperparathyroidism resulting from intrathyroidal parathyroid glands is an uncommon condition. We herein present the case of a 35-year-old woman who has been on hemodialysis for 20 years. She had renal hyperparathyroidism with generalized weakness and bone pain for 2 years. The patient initially underwent parathyroidectomy at a local institution, during which two large parathyroid glands were resected from the right side (no parathyroid glands were found on the left side); however, the surgical procedure was unsuccessful, and the patient had persistent renal hyperparathyroidism after the operation. She was then transferred to our hospital and ectopic intrathyroidal parathyroid glands were localized by neck ultrasonography and technetium-99m sestamibi scans with single-photon emission computed tomography imaging preoperatively. A left thyroid lobectomy was performed and two intrathyroidal parathyroid glands were found. The patient recovered uneventfully and her symptoms resolved. Therefore, clinicians should be aware of the possibility of renal hyperparathyroidism resulting from intrathyroidal parathyroid glands in cases where the renal hyperparathyroidism persists after parathyroidectomy.

  20. Characterization of a simplified method of cryopreserving human parathyroid tissue.

    PubMed

    Saxe, A W; Gibson, G W; Kay, S

    1990-12-01

    Cryopreservation of human parathyroid tissue plays an important role in managing difficult parathyroid disease. It also can permit investigators to conduct experiments without dependence on the operating room schedule. Availability of cryopreservation has been limited by the perceived need for expensive, complex equipment. We adapted a simple method of freezing cell suspensions to freezing human parathyroid tissue. Vials containing human parathyroid in culture media, dimethylsulfoxide, and patient serum were placed in a plastic rack in a metal pan containing prechilled (4 degrees C) ethanol and placed in a -70 degrees C freezer. We compared viability (trypan blue dye exclusion by collagenase dispersed cells) of tissue frozen in this manner to that of tissue frozen in a programmable liquid nitrogen freezer at 1 degrees C per minute, a cooling rate recommended for human parathyroid tissue. The viability of 30 patients' samples cooled in liquid nitrogen (average length of storage 5 months) was 74% +/- 15% and that of 64 patients' samples cooled in ethanol (average length of storage 26 months) was 71% +/- 15%. Viability of 19 samples of fresh tissue was 79% +/- 10%. Neither method had a statistically significant correlation between length of storage and viability. Successful cryopreservation with simplified technology may expand the availability of parathyroid tissue to meet both clinical and investigative requirements.

  1. Ultrasensitive Impedimetric Biosensor Fabricated by a New Immobilisation Technique for Parathyroid Hormone.

    PubMed

    Özcan, Hakkı Mevlüt; Yildiz, Kübra; Çakar, Cansu; Aydin, Tuba; Asav, Engin; Sağiroğlu, Ayten; Sezgintürk, Mustafa Kemal

    2015-07-01

    This paper presents a novel ultrasensitive and rapid impedimetric biosensor with new immobilisation materials for parathyroid hormone (PTH) with the aim to determine the PTH level in serum for the diagnosis and monitoring of parathyroid diseases such as hyperparathyroidism, adenoma, and thyroid cancer. The interaction between PTH and the biosensor was investigated with an electrochemical method. The biosensor was based on the gold electrode modified by mercaptohexanol (6-MHL). Anti-parathyroid hormone (anti-PTH) was covalently immobilised onto a self-assembled monolayer (SAM) by using epiclorhidrina (EPI) with ethanolamine (EA). The EPI-EA interaction represents the first use of these for the construction of biosensors in published reports. The immobilisation of the anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscopy (SEM) techniques. After the optimisation studies of immobilisation materials such as 6-MHL, EPI, EA and glutaraldehyde, linearity, repeatability and sensitivity of biosensor were evaluated as the performance of biosensor. PTH was detected within a linear range of 0.1-0.6 pg/ml, and the detection limit was 0.1 fg/ml. The specificity of the biosensor was also investigated. Finally, the described biosensor was used to detect the PTH levels in artificial serum samples.

  2. Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey

    PubMed Central

    Farwell, W. R.; Taylor, E. N.

    2013-01-01

    Summary Many determinants of parathyroid hormone (PTH) are unknown. In the National Health and Nutrition Examination Survey (NHANES), numerous factors not classically associated with calcium–phosphorus homeostasis, such as uric acid and smoking, are independently associated with PTH in adults without chronic kidney disease. Associations between serum phosphorus and PTH may vary by race. Introduction Although PTH may be an important biomarker for osteoporosis and cardiovascular disease, many determinants of PTH are unknown. We investigated associations between demographic, dietary, and serum factors and PTH level. Methods We studied 4,026 white, 1,792 black, and 1,834 Mexican-American adult participants without chronic kidney disease from the 2003–2004 and 2005–2006 NHANES. Results The mean serum PTH level was 38.3 pg/ml for whites, 42.6 pg/ml for blacks, and 41.3 pg/ml for Mexican-Americans. After adjusting for diet, body mass index, serum levels of calcium, phosphorus, 25-hydroxyvitamin D, creatinine, and other factors, smokers compared to non-smokers had lower PTH, ranging from −4.2 pg/ml (95% confidence interval (CI) −7.3 to −1.1) in Mexican-Americans to −6.1 pg/ml (95% CI −8.7 to −3.5) in blacks. After multivariate adjustment, PTH was higher in females compared to males, ranging from 1.1 pg/ml (95% CI −1.2 to 3.4) in Mexican-Americans to 4.5 pg/ml (95% CI 1.9 to 7.0) in blacks, and in older (>60 years) compared to younger participants (<30 years), ranging from 3.7 pg/ml (95% CI 1.3 to 6.1) in Mexican-Americans to 8.0 pg/ml (95% CI 5.4 to 10.7) in blacks. Higher uric acid was associated with higher PTH. In whites only, lower serum phosphorus and lower serum retinol were associated with higher PTH. Conclusions Numerous factors not classically associated with calcium–phosphorus homeostasis are independently associated with PTH and should be considered in future studies of PTH and chronic disease. Additional research is needed to elucidate

  3. Localised inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis.

    PubMed

    Gardiner, Jennifer R; Jackson, Abigail L; Gordon, Julie; Lickert, Heiko; Manley, Nancy R; Basson, M Albert

    2012-09-01

    The thymus and parathyroid glands are derived from the third pharyngeal pouch endoderm. The mechanisms that establish distinct molecular domains in the third pouch and control the subsequent separation of these organ primordia from the pharynx are poorly understood. Here, we report that mouse embryos that lack two FGF feedback antagonists, Spry1 and Spry2, display parathyroid and thymus hypoplasia and a failure of these organ primordia to completely separate from the pharynx. We show that FGF ligands and downstream reporter genes are expressed in highly regionalised patterns in the third pouch and that sprouty gene deletion results in upregulated FGF signalling throughout the pouch endoderm. As a consequence, the initiation of markers of parathyroid and thymus fate is altered. In addition, a normal apoptotic programme that is associated with the separation of the primordia from the pharynx is disrupted, resulting in the maintenance of a thymus-pharynx attachment and a subsequent inability of the thymus to migrate to its appropriate position above the heart. We demonstrate that the sprouty genes function in the pharyngeal endoderm itself to control these processes and that the defects in sprouty-deficient mutants are, at least in part, due to hyper-responsiveness to Fgf8. Finally, we provide evidence to suggest that parathyroid hypoplasia in these mutants is due to early gene expression defects in the third pouch, whereas thymus hypoplasia is caused by reduced proliferation of thymic epithelial cells in the thymus primordium.

  4. Triazolopyrimidine (trapidil), a platelet-derived growth factor antagonist, inhibits parathyroid bone disease in an animal model for chronic hyperparathyroidism

    NASA Technical Reports Server (NTRS)

    Lotinun, Sutada; Sibonga, Jean D.; Turner, Russell T.

    2003-01-01

    Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.

  5. Parathyroid-hormone-related protein in sarcoidosis.

    PubMed Central

    Zeimer, H. J.; Greenaway, T. M.; Slavin, J.; Hards, D. K.; Zhou, H.; Doery, J. C.; Hunter, A. N.; Duffield, A.; Martin, T. J.; Grill, V.

    1998-01-01

    Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis. Images Figure 1 PMID:9422518

  6. SIKs control osteocyte responses to parathyroid hormone.

    PubMed

    Wein, Marc N; Liang, Yanke; Goransson, Olga; Sundberg, Thomas B; Wang, Jinhua; Williams, Elizabeth A; O'Meara, Maureen J; Govea, Nicolas; Beqo, Belinda; Nishimori, Shigeki; Nagano, Kenichi; Brooks, Daniel J; Martins, Janaina S; Corbin, Braden; Anselmo, Anthony; Sadreyev, Ruslan; Wu, Joy Y; Sakamoto, Kei; Foretz, Marc; Xavier, Ramnik J; Baron, Roland; Bouxsein, Mary L; Gardella, Thomas J; Divieti-Pajevic, Paola; Gray, Nathanael S; Kronenberg, Henry M

    2016-10-19

    Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.

  7. SIKs control osteocyte responses to parathyroid hormone

    PubMed Central

    Wein, Marc N.; Liang, Yanke; Goransson, Olga; Sundberg, Thomas B.; Wang, Jinhua; Williams, Elizabeth A.; O'Meara, Maureen J.; Govea, Nicolas; Beqo, Belinda; Nishimori, Shigeki; Nagano, Kenichi; Brooks, Daniel J.; Martins, Janaina S.; Corbin, Braden; Anselmo, Anthony; Sadreyev, Ruslan; Wu, Joy Y.; Sakamoto, Kei; Foretz, Marc; Xavier, Ramnik J.; Baron, Roland; Bouxsein, Mary L.; Gardella, Thomas J.; Divieti-Pajevic, Paola; Gray, Nathanael S.; Kronenberg, Henry M.

    2016-01-01

    Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH. PMID:27759007

  8. Correlation between serum parathyroid hormone levels and coronary artery calcification in patients without renal failure

    PubMed Central

    Wu, Gang-Yong; Xu, Bai-Da; Wu, Ting; Wang, Xiao-Ying; Wang, Tian-Xiao; Zhang, Xiao; Wang, Xiao; Xia, Yang; Zong, Gang-Jun

    2016-01-01

    The aim of the present study was to investigate the correlation between serum parathyroid hormone (PTH) levels and coronary artery calcification (CAC) in patients without renal failure, as well as to determine independent risk factors of CAC score (CACS). A total of 157 patients who underwent coronary computed tomography angiographic examination at the 101th Hospital of the People's Liberation Army between December 2013 and February 2015 were retrospectively evaluated. The correlation between PTH levels and CACS was determined using a Pearson correlation analysis. A receiver operating characteristic (ROC) curve was drawn to determine the best cutoff PTH level for prediction of CAC. The independent association between serum PTH levels and CAC was analyzed by using a logistic regression analysis model with the response variable Be binary class. The results revealed that PTH levels in patients in the CAC group were significantly higher than those of patients in the non-calcification group. PTH levels were positively correlated with CACS (r=0.288, P<0.001). The ROC curve suggested that a PTH level of ≥31.05 pg/ml was the best cut-off point for the prediction of CAC, with a sensitivity of 80.88%, specificity of 60.67% and an area under the curve of 0.761. After including predictive factors for CAC (gender, age, smoking status, diabetes, hypertension, hyperlipidemia, body mass index, glomerular filtration rate and calcium, phosphorus, calcium-phosphorus product, magnesium, PTH, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol and C-reactive protein levels), the odds ratio of the serum PTH levels regarding the prediction of CAC was 1.050 (95% confidence interval, 1.027–1.074; P<0.001). In conclusion, the present study suggested that serum PTH levels are correlated with CAC in patients without renal failure and may thus be used as a reliable predictor of CAC. PMID:27882224

  9. Correlation between serum parathyroid hormone levels and coronary artery calcification in patients without renal failure.

    PubMed

    Wu, Gang-Yong; Xu, Bai-Da; Wu, Ting; Wang, Xiao-Ying; Wang, Tian-Xiao; Zhang, Xiao; Wang, Xiao; Xia, Yang; Zong, Gang-Jun

    2016-11-01

    The aim of the present study was to investigate the correlation between serum parathyroid hormone (PTH) levels and coronary artery calcification (CAC) in patients without renal failure, as well as to determine independent risk factors of CAC score (CACS). A total of 157 patients who underwent coronary computed tomography angiographic examination at the 101th Hospital of the People's Liberation Army between December 2013 and February 2015 were retrospectively evaluated. The correlation between PTH levels and CACS was determined using a Pearson correlation analysis. A receiver operating characteristic (ROC) curve was drawn to determine the best cutoff PTH level for prediction of CAC. The independent association between serum PTH levels and CAC was analyzed by using a logistic regression analysis model with the response variable Be binary class. The results revealed that PTH levels in patients in the CAC group were significantly higher than those of patients in the non-calcification group. PTH levels were positively correlated with CACS (r=0.288, P<0.001). The ROC curve suggested that a PTH level of ≥31.05 pg/ml was the best cut-off point for the prediction of CAC, with a sensitivity of 80.88%, specificity of 60.67% and an area under the curve of 0.761. After including predictive factors for CAC (gender, age, smoking status, diabetes, hypertension, hyperlipidemia, body mass index, glomerular filtration rate and calcium, phosphorus, calcium-phosphorus product, magnesium, PTH, total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol and C-reactive protein levels), the odds ratio of the serum PTH levels regarding the prediction of CAC was 1.050 (95% confidence interval, 1.027-1.074; P<0.001). In conclusion, the present study suggested that serum PTH levels are correlated with CAC in patients without renal failure and may thus be used as a reliable predictor of CAC.

  10. Secretion of Parathyroid Hormone in Patients with Medullary Thyroid Carcinoma

    PubMed Central

    Deftos, Leonard J.; Parthemore, Jacqueline G.

    1974-01-01

    The secretion of parathyroid hormone (PTH) and calcitonin (CT) was studied in 30 patients with medullary thyroid carcinoma. Most patients with elevated levels of CT were normocalcemic and also had normal basal levels of PTH. Five of six patients with associated hyperparathyroidism were hypercalcemic and had elevated basal PTH levels. Hormone secretion was also studied during infusions with standard and low doses of calcium. PTH unexpectedly increased during 12 of 18 calcium infusions. Such a paradoxical increase in PTH was seen in those patients with the greatest increase in CT and the least increase in calcium during the calcium infusion. Accordingly, increases in PTH concentration during the calcium infusions could be correlated directly with increases in CT and correlated inversely with increases in calcium. These observations suggest that, in some patients with medullary thyroid carcinoma, a further increase in the abnormally elevated CT levels may stimulate PTH secretion. Therefore, at least in acute studies, there may be a functional, as well as a genetic, relationship between the secretion of these two hormones in patients with this thyroid tumor. PMID:4847251

  11. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    PubMed

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions.

  12. Parathyroid and Calcium Status in Patients with Thalassemia

    PubMed Central

    Goyal, Meenu; Abrol, Pankaj

    2010-01-01

    Thirty patients with thalassemia major receiving repeated blood transfusion were studied to see their serum parathyroid hormone (PTH) and calcium status. Serum PTH, serum and 24 h urinary calcium, and serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were determined. Half of these patients, in addition to transfusion, were also supplemented with vitamin D (60,000 IU for 10d) and calcium (1500 mg/day for 3 months). Serum PTH, and serum and 24 h urinary calcium concentrations of the patients receiving transfusions were found to be significantly reduced while their serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were not significantly altered when compared to the respective mean values for the control group. Vitamin D and calcium supplementation significantly increased their serum PTH and calcium levels. Supplementations also increased urinary excretion of calcium. The results thus suggest that patients with thalassemia have hypoparathyroidism and reduced serum calcium concentrations that in turn were improved with vitamin D and calcium supplementation. PMID:21966110

  13. Serum Parathyroid Hormone Levels Predict Falls in Older Diabetic Adults

    PubMed Central

    Houston, Denise K.; Schwartz, Ann V.; Cauley, Jane A.; Tylavsky, Frances A.; Simonsick, Eleanor M.; Harris, Tamara B.; de Rekeneire, Nathalie; Schwartz, Gary G.; Kritchevsky, Stephen B.

    2008-01-01

    Objectives To examine the association between serum parathyroid hormone (PTH) levels and incident falls in older diabetic adults. Design Longitudinal analysis of incident falls over 1 year in a sub-study of diabetic participants in the Health, Aging and Body Composition study. Setting Pittsburgh, PA, and Memphis, TN. Participants Well-functioning, community-dwelling black and white adults aged 70-79 with diabetes (n = 472). Measurements Measured baseline serum PTH. Self-report of falls over the subsequent 12 months. Baseline physical performance and self-reported demographic, behavioral, and health status measures including kidney function, chronic conditions and medication use. Results 30.3% of participants reported falling over one year of follow-up. The mean ± SD baseline serum PTH was 53.5 ± 30.0 pg/mL in non-fallers and 62.6 ± 46.2 pg/mL in fallers (p = 0.01). For every 1 SD (36 pg/mL) increment in baseline serum PTH, there was approximately a 30% increased likelihood of reporting a fall in the subsequent year after adjusting for age, gender, race, field center, alcohol consumption, BMI, physical activity, and winter/spring season (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.06-1.59). Further adjustment for kidney function, chronic conditions, medication and supplement use, and physical performance attenuated the association slightly (OR (95% CI): 1.26 (1.01-1.58)). A trend remained after additional adjustment for reported falls in the previous year. Conclusion Higher serum PTH was associated with incident falls among older, well-functioning diabetic men and women. Further investigation aimed at understanding the underlying mechanism for the association between serum PTH and falls is needed. PMID:19016936

  14. Cystic parathyroid glands in MEN1: A rare entity?

    PubMed

    Cavalli, Tiziana; Giudici, Francesco; Nesi, Gabriella; Amorosi, Andrea; Santi, Raffaella; Brandi, Maria Luisa; Tonelli, Francesco

    2017-04-01

    Approximately 300 cases of sporadic parathyroid cyst (PCs) have been reported to date. Only two cases have been described in MEN1 so far. Detection by imaging could be challenging, especially in multiglandular primary hyperparathyroidism (HPT) and clinical outcome could be different. During the period 1990-2014, 71 MEN1 patients were operated for primary hyperparathyroidism in our centre. We report three cases of PCs in MEN1 patients affected by HPT, who underwent a total or subtotal parathyroidectomy with transcervical thymectomy. In our series, all three patients had an unsatisfactory postoperative course, at variance with the high percentage (over 90 %) of long-term success in MEN1 patients operated at our centre. One patient affected by cystic degeneration of all the four parathyroid glands reported persistent hypoparathyroidism, despite autografts of parathyroid tissue. For the other two cases, surgery failed to cure hyperparathyroidism, perhaps because of the presence of undetected ectopic parathyroid tissue. In the context of a multiglandular disease such as MEN1 syndrome, PCs seem rare but our experience shows about a 4 % incidence. Furthermore their presence, even in expert hands, could affect the preoperative identification of the parathyroid glands due to the difficult differential diagnosis between PC and other cystic lesions of the neck, and intraoperative detection of the glands as well as the postoperative outcome.

  15. Circulating parathyroid hormone and calcitonin in rats after spaceflight

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

    1992-01-01

    Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

  16. Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Taniguchi, Masatomo; Toyonaga, Jiro; Suehiro, Takaichi; Eriguchi, Rieko; Fujimi, Satoru; Ooboshi, Hiroaki; Kitazono, Takanari; Tsuruya, Kazuhiko

    2015-08-01

    The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland (PTG) volume has been scarcely investigated in patients with moderate to advanced secondary hyperparathyroidism (SHPT). The present study was a prospective observational study to determine the effect of cinacalcet treatment on PTG volume and serum biochemical parameters in 60 patients with renal SHPT, already treated with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical parameters and PTG volumes were performed periodically, which were analyzed by stratification into tertiles across the baseline parathyroid hormone (PTH) level or PTG volume. We also determined the factors that can estimate the changes in PTG volume and the achievement of the target PTH range by multivariable analyses. Two years of cinacalcet treatment significantly decreased the serum levels of PTH, calcium, and phosphate, followed by the improvement of achieving the target ranges for these parameters recommended by the Japanese Society for Dialysis Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and also decreased the serum PTH level independent of the baseline serum PTH level and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2 years. Multivariable analysis showed that patients with nodular PTG at baseline and patients with higher serum calcium and PTH levels at 1 year were likely to exceed the target range of PTH at two years. In conclusion, cinacalcet treatment with intravenous VDRA therapy decreased both PTG volume and serum intact PTH level, irrespective of the pretreatment PTG status and past treatment history.

  17. Effect of reconstruction algorithms on the accuracy of 99mTc sestamibi SPECT/CT parathyroid imaging

    PubMed Central

    Nichols, Kenneth J; Tronco, Gene G; Palestro, Christopher J

    2015-01-01

    The superiority of SPECT/CT over SPECT for 99mTc-sestamibi parathyroid imaging often is assumed to be due to improved lesion localization provided by the anatomic component (computed tomography) of the examination. It also is possible that this superiority may be related to the algorithms used for SPECT data reconstruction. The objective of this investigation was to determine the effect of SPECT reconstruction algorithms on the accuracy of MIBI SPECT/CT parathyroid imaging. We retrospectively analyzed preoperative MIBI SPECT/CT parathyroid imaging studies performed on 106 patients. SPECT data were reconstructed by filtered back projection (FBP) and by iterative reconstruction with corrections for collimator resolution recovery and attenuation (IRC). Two experienced readers independently graded lesion detection certainty on a 5-point scale without knowledge of each other’s readings, reconstruction methods, other test results or final diagnoses. All patients had surgical confirmation of the final diagnosis, including disease limited to the neck, and location and weight of excised lesion(s). There were 135 parathyroid lesions among the 106 patients. For FBP SPECT/CT and IRC SPECT/CT sensitivity was 76% and 90% (p = 0.003), specificity was 87% and 87% (p = 0.90), and accuracy was 83% and 88% (p = 0.04), respectively. Inter-rater agreement was significantly higher for IRC than for FBP (kappa = 0.76, “good agreement”, versus kappa = 0.58, “moderate agreement”, p < 0.0001). We conclude that the improved accuracy of MIBI SPECT/CT compared to MIBI SPECT for preoperative parathyroid lesion localization is due in part to the use of IRC for SPECT data reconstruction. PMID:25973340

  18. Parathyroid hormone in sodium-dependent hypertension

    SciTech Connect

    Doris, P.A.; Harvey, S.; Pang, P.K.T.

    1987-09-14

    Plasma parathyroid hormone (pPTH) levels have been assessed in three separate radioimmunoassay systems in samples from Wistar-Kyoto rats. The animals were subjected to one of three dietary regimens throughout the study period: Group 1 animals consumed normal rat chow and drank tap water; Group 2 animals consumed normal rat chow and tap water was replaced with 0.05% saline solution; Group 3 animals consumed normal rat chow to which 2.5% CaCO/sub 3/ had been added and also drank 0.5% saline solution. Three assay systems were used to measure pPTH levels from trunk blood samples obtained by guillotine decapitation. One assay used an antiserum directed toward the vasoactive N terminal fragment 1-34 and produced pPTH measurements of 0.74 +/- 0.05 ng/ml in Gp 1 animals, 1.04 +/- 0.07 ng/ml in Gp 2 animals and 1.12 +/- 0.08 ng/ml in Gp 3 animals. This pattern was consistent with that obtained by another antiserum which had been raised against the intact 1-84 PTH molecule and produced values of 0.25 +/- 0.03 ng/ml in Gp 1 animals, 0.55 +/- 0.07 ng/ml in Gp 2 animals and 0.74 +/- 0.04 ng/ml in Gp 3 animals. Antiserum raised against the C-terminal did not show any difference in pPTH across groups. The authors conclude that saline consumption may increase some portions of circulating PTH. 26 references, 2 tables.

  19. Anatomy of thyroid and parathyroid glands and neurovascular relations.

    PubMed

    Mohebati, A; Shaha, A R

    2012-01-01

    Historically, thyroid surgery has been fraught with complications. Injury to the recurrent laryngeal nerve, superior laryngeal nerve, or the parathyroid glands may result in profound life-long consequences for the patient. To minimize the morbidity of the operation, a surgeon must have an in-depth understanding of the anatomy of the thyroid and parathyroid glands and be able to apply this information to perform a safe and effective operation. This article will review the pertinent anatomy and embryology of the thyroid and parathyroid glands and the critical structures that lie in their proximity. This information should aid the surgeon in appropriate identification and preservation of the function of these structures and to avoid the pitfalls of the operation.

  20. Parathyroid gland of the freshwater snake Natrix piscator Schneider.

    PubMed

    Singh, R; Kar, I

    1983-07-01

    The structure and function of the parathyroid glands of freshwater snake, Natrix piscator, were studied. N. piscator has two pairs of parathyroid glands which are composed of cell cords of typical endocrine appearance, and follicles are absent. Parathyroidectomy was followed by significant (P less than 0.001) hypocalcemia and hyperphosphatemia throughout the 5th week of experimental period. Following parathyroidectomy, calcium and phosphate concentrations in bone were significantly (P less than 0.05) increased after 5 weeks; however, these values in muscle were not significantly changed. Tetany was also observed in parathyroidectomized snakes. Histological structure and function of the glands do not appear to vary seasonally. Administration of parathyroid gland extract of this ophidian reptile into rats caused significant (P less than 0.05) elevation of serum calcium.

  1. Image diagnosis of parathyroid glands in chronic renal failure

    SciTech Connect

    Takagi, H.; Tominaga, Y.; Uchida, K.; Yamada, N.; Morimoto, T.; Yasue, M.

    1983-07-01

    Twenty-two out of 31 patients with chronic renal failure and secondary hyperparathyroidism who underwent parathyroidectomy before operation underwent non-invasive image diagnosis of parathyroid glands by computed tomography (CT), scintigraphy with /sup 201/TlCl and /sup 99m/TcO/sup 4 +/, and/or ultrasonography. CT visualized 39 of 45 parathyroid glands (86.7%), weighing more than 500 mg. Scintigraphy with a subtraction method using a computer performed the diagnosis in 19 of 27 glands (70.4%). Ultrasonography detected 21 of 27 glands (77.8%). Image diagnosis was also useful in the postoperative follow-up study. The non-invasive image diagnosis of parathyroid glands in patients with chronic renal failure is thus valuable for 1) definite diagnosis of secondary hyperparathyroidism, 2) localization, and 3) diagnosis for effectiveness of conservative treatment.

  2. [Giant parathyroid adenoma causing early recurrence of renal stones].

    PubMed

    Traxer, Olivier; Mouton, Albert; Abbecassis, Rémy; Tassard, Marc; Vigneau, Cécile; Gattegno, Bernard; Thibault, Philippe

    2004-06-01

    Primary hyperparathyroidism (PHPT) is not a rare disease. Renal stones are the most frequent complication of PHPT The authors report the case of a patient with giant parathyroid adenoma responsible for early recurrence of renal stones. Ultrasound examination of the neck, parathyroid MRI and Technetium99m-Sestamibi scintigraphy confirmed the parathyroid adenoma. Surgical exploration allowed resection of a giant adenoma (6.5 x 2.5 x 1.5 cm weighing 17 g). In the light of this case, the authors describe the characteristics of HPT define the place of preoperative imaging and emphasize the need for systematic aetiological work-up looking for HPT in all patients with a first episode of renal stones.

  3. Diagnosis and surgical treatment of mediastinal parathyroid tumors.

    PubMed Central

    Rothmund, M; Diethelm, L; Brünner, H; Kümmerle, F

    1976-01-01

    Experience and problems in the localization, diagnosis and surgical treatment of mediastinal parathyroid tumors are reported. Arteriography, pneumomediastinum and, especially, selective blood withdrawal with assay of parathyroid hormone, have proven valuable to the authors. Scintigram, intravital staining methods and venography are less productive. Retrosternal parathyroid tumors that can be removed from a Kocher incision should not, for practical reasons, be classified with the mediastinal tumors. The authors recommend the one-phase operation. If, after an intensive search of the neck and behind the sternum, no tumor has been found, it is advisable to incise the sternum step by step and revise the anterior mediastinum in the same session. Images Fig. 1a. Fig. 1b. Figs. 2 a and b. Fig. 3. PMID:1247311

  4. A clinical audit of thallium-technetium subtraction parathyroid scans.

    PubMed Central

    Samanta, A.; Wilson, B.; Iqbal, J.; Burden, A. C.; Walls, J.; Cosgriff, P.

    1990-01-01

    Eighty six consecutive thallium-technetium subtraction parathyroid scans performed over a three year period for hypercalcaemia have been evaluated. Twelve had chronic renal failure, 11 had hypercalcaemia due to non-hyperparathyroid causes and in 10 the imaging study was technically inadequate. The remaining 53 technically adequate studies performed for hypercalcaemia clinically thought to be possibly due to hyperparathyroidism have been analysed. Of 20 (38%) positive scans, 13 came to surgery (10 correctly localized parathyroid adenomas, 2 with multiple gland hyperplasia, and 1 papillary carcinoma of the thyroid). Of 33 (62%) negative scans, 9 had surgical exploration on the basis of strong clinical grounds and all had parathyroid adenomas. Multiple biochemical parameters have been assessed in relation to a positive outcome on scan. The adjusted calcium-phosphate product and the ratio of the adjusted calcium-phosphate product to creatinine (Ca x P/Cr) were both significantly lower in the scan positive group (P less than 0.01). The scan positive group had a significantly higher mean level of PTH (P less than 0.001) and lower mean level of phosphate (P less than 0.001). The present experience shows that parathyroid imaging is useful in localizing parathyroid adenomas in 50% of cases (10 out of 19). This figure is at the lower end of the range of previously published results. It is less effective in demonstrating multiple gland hyperplasia. The decision as to whether to undertake surgical exploration when the scan is negative has been based successfully on clinical judgement. We feel that an analysis of this nature is important, as it gives insights into the practical relevance of parathyroid imaging in the context of routine clinical work. PMID:2170959

  5. Pathogenesis of renal calculi in distal renal tubular acidosis. Possible role of parathyroid hormone.

    PubMed

    Lee, D B; Drinkard, J P; Gonick, H C; Coulson, W F; Cracchiolo, A

    1976-01-01

    Elevated circulating levels of immunoreactive parathyroid hormone (PTH), hypercalciuria and renal calculi were found in 3 patients with distal renal tubular acidosis (RTA). Treatment with alkali resulted in a fall of PTH toward normal and a reduction in urinary calcium, but the frequency of urolithiasis was unchanged. In one patient in whom prolonged follow-up was possible, a subtotal parathyroidectomy was performed. This was followed by virtual cessation of stone formation despite persistence of the acidification defect. This study suggests that RTA may be associated with secondary hyperparathyroidism and that the consequent elevation in PTH may play a contributory role in the pathogenesis of renal calculi.

  6. Significance of rebounding parathyroid hormone levels during parathyroidectomy

    PubMed Central

    Schneider, David F.; Ojomo, Kristin A.; Mazeh, Haggi; Oltmann, Sarah C.; Sippel, Rebecca S.; Chen, Herbert

    2013-01-01

    BACKGROUND Using minimally invasive parathyroidectomy (MIP), most surgeons require a 50% decline in intraoperative parathyroid hormone (IoPTH) to determine cure, but the significance of IoPTH kinetics occurring after this drop remains unknown. The aim of this study was to determine the impact of IoPTH levels that first meet criteria for cure, but then increase again, or rebound, between 10 and 15 minutes post-excision. METHODS We conducted a retrospective review of patients undergoing initial parathyroidectomy for primary hyperparathyroidism at our institution from 2001 – 2011. Rebound IoPTH was defined as an increase in PTH ≥ 5 pg/mL after achieving the 50% drop required for cure. Comparisons were evaluated with the student's t-test, Chi-squared test, or Fisher's exact test where appropriate. RESULTS Of the 1,386 patients who met selection criteria, 86 (6.2%) patients exhibited rebound IoPTH. The mean magnitude of rebound was 13.8 ± 3.6 pg/mL. Compared to those not displaying rebound, more patients with rebound IoPTH were treated with open parathyroidectomy rather than MIP (10.8% vs. 4.5%, p<0.01). The recurrence rate among those with rebound IoPTH was more than double that of patients without rebound IoPTH (5.8% vs. 2.2%, p = 0.03). Magnitude of rebound, however, did not correlate with recurrence. The rate of persistent disease was not different between those with and without rebound IoPTH. Rebound was a much better indicator of recurrence than patients whose final IoPTH levels were not within the normal range. CONCLUSIONS Rebound IoPTH is more common in patients who develop recurrent hyperparathyroidism. Therefore, surgeons should closely monitor patients with rebound IoPTH for disease recurrence. PMID:23669749

  7. Vitamin D and Parathyroid Hormone Relationships with Urinary Nitric Oxide Metabolites and Plasma Isoprostanes in African-Americans

    PubMed Central

    Valiña-Tóth, Anna Liza; Lai, Zongshan; Zhang, Shilling; Flack, John M.

    2012-01-01

    Background Vitamin D deficiency and secondary rises in parathyroid hormone (PTH) are highly prevalent in obese African-Americans. Endothelial dysfunction related to oxidative stress is more common in African-Americans compared to whites. Currently, the association of vitamin D (25-hydroxyvitamin D, 25-OH D) and PTH to nitric oxide metabolites (NOx) – nitrate and nitrite – and oxidative stress in African-Americans is unknown. Objective: A cross-sectional design was utilized to determine the association of 25-OH D and PTH with urinary NOx (UNOx) (n = 101) and plasma isoprostanes (n = 125), an oxidative stress marker, in overweight (body mass index of 25–39.9), normotensive African-Americans aged ≥35 years. Measurements: Multivariable linear regression analysis adjusted for age, sex, body mass index, and season was used to determine the relationship of 25-OH D and PTH to UNOx and isoprostanes. General linear models, adjusted for the same covariates, contrasted UNOx across three mutually exclusive vitamin D/PTH groups: (1) normal 25-OH D (51–249 nmol/l) and normal PTH (≤65 pg/ml); (2) low 25-OH D and normal PTH, and (3) low 25-OH D and high PTH. Results 25-OH D was directly associated with UNOx before (p = 0.02) and after (p = 0.03) adjustment for PTH levels. A borderline significant association was observed between PTH and isoprostanes (p = 0.08). UNOx was 424, 290, and 270 μmol/8 h, respectively, across vitamin D/PTH groups 1–3 (p = 0.08). Conclusion 25-OH D was directly associated with NO availability and PTH was positively, though borderline, associated with isoprostanes in overweight, normotensive adult African-Americans. PMID:22969780

  8. Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses.

    PubMed

    Toribio, Ramiro E; Kohn, Catherine W; Sams, Richard A; Capen, Charles C; Rosol, Thomas J

    2003-02-15

    Abnormalities in calcium (Ca(2+)) homeostasis are reported in horses with several pathological conditions; however, there is little information on Ca(2+) regulation in horses. The objectives of the present study were to determine the Ca(2+) set-point in healthy horses, to determine whether the Ca(2+)/parathyroid hormone (PTH) response curves were characterized by hysteresis, and to determine if the order of experimentally induced hypocalcemia or hypercalcemia had an effect on PTH secretion. The Ca(2+) set-point and hysteresis were determined in 12 healthy horses by infusing Na(2)EDTA and calcium gluconate. The Ca(2+) set-point was 1.37 +/- 0.05 mmol/L, which is higher than values reported for humans and dogs (1.0-1.2 mmol/L). Hysteresis was present during hypocalcemia and hypercalcemia. Horses in which hypocalcemia was followed by hypercalcemia secreted more PTH (7440 +/- 740 pmol min/L) than horses in which hypercalcemia was followed by hypocalcemia (5990 +/- 570 pmol min/L). This study has demonstrated that the Ca(2+) set-point in the horse is higher than in other domestic animals and man. We have shown that the Ca(2+)/PTH relationship in horses is sigmoidal and displays hysteresis during both hypocalcemia and hypercalcemia, and that extracellular Ca(2+) concentrations may affect the response of the parathyroid gland to hypocalcemia.

  9. Effect of prostaglandin E1 on certain renal actions of parathyroid hormone

    PubMed Central

    Beck, Nama P.; DeRubertis, Frederick R.; Michelis, Michael F.; Fusco, Robert D.; Field, James B.; Davis, Bernard B.

    1972-01-01

    Parathyroid hormone increased basal adenyl cyclase activity and that increase was inhibited by prostaglandin E1 (PGE1). Tissue cyclic 3′,5′-adenosine monophosphate (cyclic AMP) concentrations were increased by parathyroid hormone and that increase was likewise inhibited by PGE1. Both parathyroid hormone and dibutyryl cyclic AMP increased 32P incorporation into renal cortical phospholipids. PGE1 diminished the effect of parathyroid hormone but not dibutyryl cyclic AMP to influence that parameter. PGE1 likewise modulated the effect of parathyroid hormone but not dibutyryl cyclic AMP to decrease fractional phosphate reabsorption by the renal tubule. It is suggested that PGE1 inhibits the effect of parathyroid hormone by decreasing its effect on adenyl cyclase. Such interaction may be important in modulating the intracellular action of parathyroid hormone on kidney cortex. PMID:4344730

  10. 21 CFR 862.1545 - Parathyroid hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Parathyroid hormone test system. 862.1545 Section 862.1545 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...) resulting from disorders of calcium metabolism. (b) Classification. Class II....

  11. Parathyroid hormone 1-34 and skeletal anabolic action

    PubMed Central

    Sanghani, A.; Coathup, M.; Briggs, T.; Bostrom, M.; Blunn, G.

    2017-01-01

    Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect. Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1. PMID:28062525

  12. Impact of hybrid SPECT/CT imaging on the detection of single parathyroid adenoma

    NASA Astrophysics Data System (ADS)

    Morrison, Antony; Brennan, Patrick C.; Reed, Warren; Pietrzyk, Mariusz; Schembri, Geoff; Bailey, Elizabeth; Roach, Paul; Evanoff, Michael; Kench, Peter L.

    2011-03-01

    Objective: The aim of this investigation is to determine the impact of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) on the detection of parathyroid adenoma. Materials and methods: 16 patients presented with suspected parathyroid adenoma localised within the neck. All patients were injected with Tc-99m sestamibi and were scanned with a GE Infinia Hawkeye SPECT/CT. There were six negative and ten positive confirmed cases. Five expert radiologists specializing in nuclear medicine were asked to report on the 16 planar and SPECT data sets and were then asked to report on the same randomly ordered data sets with the addition of CT. Receiver operating characteristic (ROC) analysis was performed using the Dorfman-Berbaum-Metz multireadermulticase methodology and sensitivity and specificity values were generated. A significance level of p <= 0.05 was set for all comparisons. Results: ROC analysis demonstrated an AUC of 0.64 and 0.69 for SPECT and SPECT/CT respectively (p = 0.31). Mean sensitivity scores increased from 0.64 to 0.80 (p = 0.17) and specificity scores decreased from 0.57 to 0.40 (p = 0.17) with the addition of the CT data. Conclusion: This preliminary investigation suggests that extra CT information may increase lesion detection as well as false positive rates for SPECT-based investigations of a single parathyroid adenoma. However the difference in diagnostic efficacy between the two groups was not found to be statistically significant therefore requiring further investigation. These findings have implications beyond the clinical situation described here.

  13. Parathyroid autotransplantation during total thyroidectomy. Results of a retrospective study.

    PubMed

    Tartaglia, Francesco; Blasi, Sara; Giuliani, Alessandro; Merola, Raffaele; Livadoti, Giada; Krizzuk, Dimitri; Tortorelli, Giovanni; Tromba, Luciana

    2016-04-01

    Authors analyze their experience of parathyroid autotransplantation during total thyroidectomy, with the purpose of seeing whether this practice influenced the rate of postoperative hypocalcemia and/or hypoparathyroidism. We identified three groups of patients: group A, consisting of 57 patients, underwent parathyroid autotransplantation during total thyroidectomy; group B consisting of 87 patients not submitted to intraoperative autotransplantation in whom, as an incidental finding, a parathyroid gland was detected in the surgical specimen; group C consisted of 100 patients who did not undergo autotransplantation and whose surgical specimens were not found to contain parathyroid glands. The three groups were compared for sex and age as well as for a series of clinical and laboratory parameters on the first three postoperative days and at six months after surgery. The rate of permanent hypoparathyroidism was 3.5% in Group A, 3.45% in Group B, and 1% in Group C. Multivariate analysis revealed that all three groups showed postoperative recovery of calcium levels, although the rate and extent of this recovery differed between them. The control group showed a more rapid and more complete recovery of serum calcium values compared with Groups A and B. Calcium recovery in Groups A and B was comparable, in terms of both rate and extent. The same pattern of results emerged for the iPTH values. The analysis of the data showed that there were no significant differences in the analyzed parameters between Groups A and B. This suggests that parathyroid autotransplantation does not influence the rate of postoperative hypocalcemia and/or hypoparathyroidism.

  14. An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In adults, maximal suppression of serum parathyroid hormone (PTH) has commonly been used to determine the sufficiency of serum 25-hydroxyvitamin D [25(OH) D]. In children and adolescents, the relationship between serum 25(OH) D and PTH is less clear, and most studies reporting a relationship are der...

  15. Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To determine the effect of vitamin D (VITD) supplementation on tubular reabsorption of phosphate (TRP), serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), and C telopeptide (CTX) in HIV-infected youth receiving and not receiving tenofovir-containing cART (TDF). Design: Ra...

  16. Evidence of a stabilizing mutation of β-catenin encoded by CTNNB1 exon 3 in a large series of sporadic parathyroid adenomas.

    PubMed

    Starker, Lee F; Fonseca, Annabelle L; Fonseca, Annabelle; Akerström, Göran; Björklund, Peyman; Westin, Gunnar; Carling, Tobias

    2012-12-01

    Aberrant accumulation of β-catenin plays an important role in a variety of human neoplasms. This can be caused by stabilizing mutation of β-catenin (CTNNB1, exon 3) or by mutation or deregulated expression of other components of the WNT/β-catenin signaling pathway. Accumulation of non-phosphorylated active β-catenin has been reported to commonly occur in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT), either due to the aberrantly spliced internally truncated WNT receptor LRP5 (LRP5Δ) or to a stabilizing mutation of β-catenin. The S37A mutation was reported to occur in 7.3 % in a single study of parathyroid adenomas, while in other studies no stabilizing mutations of β-catenin exon 3 were identified. The aim of this study was to determine the mutational frequency of the CTNNB1 gene, specifically exon 3 in a large series of parathyroid adenomas. One hundred and eighty sporadic parathyroid adenomas were examined for mutations in exon 3 of CTNNB1 by direct DNA sequencing, utilizing previously published primer sequences. The mutation S33C (TCT>TGT) was detected by direct-DNA sequencing of PCR fragments in 1 out of 180 sporadic parathyroid adenomas (0.68 %). Like serine 37, mutations of serine 33 have been reported in many neoplasms with resulting β-catenin stabilization, enhanced transcription, and oncogenic activities. Immunohistochemical analysis revealed an overexpression of the β-catenin protein in the lone mutant tumor. Taking also previous studies into account we conclude that activating mutations of the regulatory GSK-3β phosphorylation sites serine 33 and 37, encoded by CTNNB1 exon 3, rarely occur in parathyroid adenomas from patients with pHPT.

  17. The risk of hypocalcemia in patients with parathyroid autotransplantation during thyroidectomy

    PubMed Central

    Oran, Ebru; Yetkin, Gürkan; Mihmanlı, Mehmet; Celayir, Fevzi; Aygün, Nurcihan; Çoruh, Bestegül; Peker, Evren; Uludağ, Mehmet

    2016-01-01

    Objective: Thyroidectomy is the most common cause of hypocalcemia. Preservation of parathyroid glands in situ is essential in preventing this complication. The aims of our study were to review patients who underwent parathyroid gland autotransplantation during thyroidectomy, and to compare hypocalcemia rates in patients with and without autotransplantation. Material and Methods: Parathyroid gland autotransplantation was performed in 43 (7.9%) of 543 patients who underwent thyroidectomy between 2008 and 2012. Results: Forty-four parathyroid glands were autotransplanted in 43 patients, including 36 women and 7 men. The median age was 55 (range: 30 to 68). The most common cause of autotransplantation was vascular comprise of the parathyroid gland. Early postoperative hypocalcemia developed in 37% of patients with autotransplantation, and none developed permanent hypocalcemia. Transient and permanent hypocalcemia rates were 9.6% and 0.4% in patients without autotransplantation, respectively. The risk of transient hypocalcemia was significantly high in patients with parathyroid autotransplantation (p<0.001). There was no difference between the two groups in terms of permanent hypocalcemia (p=0.156). Conclusion: Despite meticulous dissection, parathyroid glands can be devascularized or removed inadvertently during thyroidectomy. Parathyroid autotransplantation is the best method to maintain parathyroid gland function. Although the risk of transient hypocalcemia is increased following parathyroid autotransplantation, long-term results are satisfactory. PMID:26985153

  18. Modification of the analysis of parathyroid hormone-related protein in milk and concentrations of this protein in commercial milk and milk products in Japan.

    PubMed

    Onda, K; Yamaguchi, M; Ohashi, M; Sato, R; Ochiai, H; Iriki, T; Wada, Y

    2010-05-01

    Parathyroid hormone-related protein (PTHrP), which causes hypercalcemia associated with malignant tumors, is known to be present in milk. Gene expression of PTHrP in the mammary gland increases markedly during parturition and with the onset of lactation. Even when circulating PTHrP levels are extremely low or below the detection limit, milk PTHrP levels are remarkably high. Parathyroid hormone-related protein derived from the mammary gland is assumed to play a role in maintaining the maternal calcium homeostasis and calcium transport from blood to milk. In previous studies that determined the PTHrP concentrations in milk, the pretreatments and diluent composition were not standardized. Here, we investigated the effect of various pretreatment procedures and diluent constitutions and the consequent PTHrP concentrations in commercial milk and milk products in Japan. Significant differences were found in PTHrP concentrations in raw milk samples subjected to different combinations of pretreatments (mixing, centrifugation, acidification, and heating) and diluents (0pM standard solution of PTHrP, plasma treated with protease inhibitors, and original diluent). We measured the PTHrP concentrations in normal liquid milk, processed milk, milk drinks, formulated milk powders, and skim milk powder by using the appropriate combination of pretreatment (acidification) and diluent (plasma treated with protease inhibitors). The PTHrP concentration in normal liquid milk, processed milk, and skim milk powder was as high as that in raw milk (>5nM), whereas that in milk drinks differed considerably. The PTHrP concentration in infant formulas (<2nM) was lower than that in the other milk products. These results indicate that a certain amount of PTHrP is ingested when milk and milk products are consumed.

  19. Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women.

    PubMed

    Bolland, Mark J; Grey, Andrew B; Ames, Ruth W; Horne, Anne M; Gamble, Greg D; Reid, Ian R

    2006-03-01

    Previously, we reported that people with elevated parathyroid hormone (PTH) levels due to primary hyperparathyroidism have increased body weight compared to eucalcemic controls. We sought to determine whether the same relationship between PTH and body weight exists in eucalcemic healthy postmenopausal women, and to investigate the relationships between components of body weight, PTH, vitamin D metabolites, and metabolic indices. We performed a cross-sectional analysis of 116 healthy community-dwelling postmenopausal women. Pearson correlation analysis was used to test for univariate linear relationships between variables, and stepwise multiple regression analysis to assess for multivariate relationships. We found that PTH was significantly positively correlated with body weight, regional and total fat mass, and percent body fat, and negatively correlated with activity levels, 25 hydroxyvitamin D (25OHD), dietary calcium intake, and serum phosphate. On multivariate analysis, PTH was positively related to percent body fat (P = 0.020; partial r2 = 0.10) and negatively related to dietary calcium intake (P = 0.041; partial r2 = 0.03) and serum phosphate (P = 0.026; partial r2 = 0.04). Adjusting for vitamin D insufficiency or 25OHD levels did not affect the relationship between PTH and fat mass. For 25OHD, there were significant positive correlations with lumbar spine BMD and serum albumin, and significant negative correlations with PTH, total fat mass, trunk fat, and pelvic fat. On multivariate analysis, 25OHD was positively related to serum albumin (P = 0.008; partial r2 = 0.07) and negatively related to pelvic fat mass (P = 0.014; partial r2 = 0.05). Adjusting for PTH levels did not change the relationship between 25OHD and pelvic fat mass. We conclude that fat mass is a significant independent determinant of serum PTH levels, and that this relationship is independent of the inverse relationship between 25OHD and fat mass. This association between fat mass and PTH

  20. Characterization of the major parathyroid hormone target cell in the endosteal metaphysis of rat long bones

    SciTech Connect

    Rouleau, M.F.; Mitchell, J.; Goltzman, D. )

    1990-10-01

    The majority of in vivo competitive binding of parathyroid hormone (PTH) in the endosteal metaphysis of rat long bones was recently shown to be localized in the intertrabecular tissue to a cell that is distinct from a differentiated osteoblast. In the present report we have further characterized this cell, termed a parathyroid hormone target (PT) cell, by light and electron microscopy using radioautography and histochemical techniques. These studies demonstrate that the PT cell is a mononuclear cell with a large cell body located at times between clusters of differentiated osteoblasts, as well as in other regions of the intertrabecular tissue. Its long cytoplasmic processes extend from the bone matrix through the intertrabecular region toward vascular structures, interdigitating with various cells of the endosteum. A distinctive tubular structure originating in the Golgi system and often associated with long mitochondria and glycogen particles extends throughout the cytoplasmic processes of the PT cell. Based on its capacity to incorporate ({sup 3}H)thymidine, the PT cell appears to divide rather slowly. The identification of occasional hybrid cells with ultrastructural features of both the PT cell and the differentiated osteoblast and the presence of histochemical evidence for alkaline phosphatase activity suggest that the PT cell is of the osteoblast lineage. These studies therefore morphologically define a major osseous target cell for PTH that, although of the osteoblast lineage, is not a differentiated osteoblast and provide in vivo evidence that characteristics of the 'osteoblast phenotype' are not restricted to a sole osseous cell type.

  1. Bisphosphonates, vitamin D, parathyroid hormone, and osteonecrosis of the jaw. Could there be a missing link?

    PubMed Central

    Leizaola-Cardesa, Ignacio-Osoitz; Aguilar-Salvatierra, Antonio; Gonzalez-Jaranay, Maximino; Moreu, Gerardo; Sala-Romero, María-José

    2016-01-01

    It is estimated that over 190 million bisphosphonates have been prescribed worldwide. But this drug can produce adverse effects, of which osteonecrosis of the jaw and severe hypocalcemia are the most serious. It is evident that bisphosphonate administration affects multiple and diverse biochemical mediators related to bone metabolism. This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. The imbalances generated by vitamin D and calcium deficiencies, together with their multiple systemic repercussions, have been widely researched but the outcomes of these imbalances in relation to bisphosphonate administration are not well known, and some research has indicated that they may be associated with osteonecrosis of the jaw (ONJ). The present review set out to explain the functioning of bone metabolism, the importance of different chemical mediators, the imbalances produced by incorrect use of this drug, in order to forewarn against the possible relation of these parameters with ONJ, whose physiopathology remains unknown. Medical and dental clinics should keep detailed anamneses of the use of vitamin D and calcium supplements, as it is of vital importance to maintain their correct levels in blood, given that these are related to ONJ as well as other adverse effects; this procedure is also necessary in order to ensure the correct use of the drug. Key words:Bisphosphonate-related osteonecrosis of the jaw, vitamin D, parathyroid hor PMID:26827062

  2. Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.

    PubMed Central

    Delmez, J A; Tindira, C; Grooms, P; Dusso, A; Windus, D W; Slatopolsky, E

    1989-01-01

    Numerous in vitro studies in experimental animals have demonstrated a direct suppressive effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on parathyroid hormone (PTH) synthesis. We therefore sought to determine whether such an effect could be demonstrated in uremic patients undergoing maneuvers designed to avoid changes in serum calcium concentrations. In addition, the response of the parathyroid gland in patients undergoing hypercalcemic suppression (protocol I) and hypocalcemic stimulation (protocol II) before and after 2 wk of intravenous 1,25(OH)2D was evaluated. In those enlisted in protocol I, PTH values fell from 375 +/- 66 to 294 +/- 50 pg (P less than 0.01) after 1,25(OH)2D administration. During hypercalcemic suppression, the "set point" (PTH max + PTH min/2) for PTH suppression by calcium fell from 5.24 +/- 0.14 to 5.06 +/- 0.15 mg/dl (P less than 0.05) with 1,25(OH)2D. A similar decline in PTH levels after giving intravenous 1,25(OH)2D was noted in protocol II patients. During hypocalcemic stimulation, the parathyroid response was attenuated by 1,25(OH)2D. We conclude that intravenous 1,25(OH)2D directly suppresses PTH secretion in uremic patients. This suppression, in part, appears to be due to increased sensitivity of the gland to ambient calcium levels. PMID:2703535

  3. Recombinant production of TEV cleaved human parathyroid hormone.

    PubMed

    Audu, Christopher O; Cochran, Jared C; Pellegrini, Maria; Mierke, Dale F

    2013-08-01

    The parathyroid hormone, PTH, is responsible for calcium and phosphate ion homeostasis in the body. The first 34 amino acids of the peptide maintain the biological activity of the hormone and is currently marketed for calcium imbalance disorders. Although several methods for the production of recombinant PTH(1-34) have been reported, most involve the use of cleavage conditions that result in a modified peptide or unfavorable side products. Herein, we detail the recombinant production of (15) N-enriched human parathyroid hormone, (15) N PTH(1-34), generated via a plasmid vector that gives reasonable yield, low-cost protease cleavage (leaving the native N-terminal serine in its amino form), and purification by affinity and size exclusion chromatography. We characterize the product by multidimensional, heteronuclear NMR, circular dichroism, and LC/MS.

  4. Pathologic Fractures: A Neglected Clinical Feature of Parathyroid Adenoma

    PubMed Central

    Abshirini, Hassan; Rashidi, Iran; Saki, Nader

    2010-01-01

    The pattern of clinical presentation of primary hyperparathyroidism (pHPT) has changed dramatically from a severe disease to an asymptomatic condition in Western countries. The story is completely different in Eastern countries. Bone and joint related sign and symptoms like bone pain and multiple fractures are common in these patients. Imaging and nuclear medicine studies will be helpful specially in patient who candidate for surgical removal of the abnormal parathyroid gland. Here, we present a 48-year-old man with multiple typical fractures in long bones and a single adenoma in his right inferior parathyroid gland. pHPT is a severe, symptomatic disease with serious complications and high morbidity in Iran. Advanced skeletal disease is the most common pattern of presentation. PMID:21209742

  5. Cancer associated proteins in blood plasma: Determining normal variation.

    PubMed

    Stenemo, Markus; Teleman, Johan; Sjöström, Martin; Grubb, Gabriel; Malmström, Erik; Malmström, Johan; Niméus, Emma

    2016-07-01

    Protein biomarkers have the potential to improve diagnosis, stratification of patients into treatment cohorts, follow disease progression and treatment response. One distinct group of potential biomarkers comprises proteins which have been linked to cancer, known as cancer associated proteins (CAPs). We determined the normal variation of 86 CAPs in 72 individual plasma samples collected from ten individuals using SRM mass spectrometry. Samples were collected weekly during 5 weeks from ten volunteers and over one day at nine fixed time points from three volunteers. We determined the degree of the normal variation depending on interpersonal variation, variation due to time of day, and variation over weeks and observed that the variation dependent on the time of day appeared to be the most important. Subdivision of the proteins resulted in two predominant protein groups containing 21 proteins with relatively high variation in all three factors (day, week and individual), and 22 proteins with relatively low variation in all factors. We present a strategy for prioritizing biomarker candidates for future studies based on stratification over their normal variation and have made all data publicly available. Our findings can be used to improve selection of biomarker candidates in future studies and to determine which proteins are most suitable depending on study design.

  6. Sonography of Normal and Abnormal Thyroid and Parathyroid Glands.

    PubMed

    Andrioli, Massimiliano; Valcavi, Roberto

    2016-01-01

    Ultrasonography (US) represents the most sensitive and efficient method for the evaluation of the thyroid and parathyroid glands. Infectious and autoimmune thyroiditis are common diseases, usually diagnosed and followed up by clinical examination and laboratory analyses. Nevertheless, US plays an important role in confirming diagnoses, predicting outcomes and, in autoimmune hyperthyroidism, in titrating therapy. Conversely, in nodular thyroid disease US is the imaging method of choice for the characterization and surveillance of lesions. It provides consistent clues in predicting the risk of malignancy, thus directing patient referral for fine-needle aspiration (FNA) biopsy. Suspicious US features generally include marked hypoechogenicity, a shape taller than it is wide, ill-defined or irregular borders, microcalcifications and hardness at elastographic evaluation. Finally, the role of US in thyroid cancer is to evaluate extension beyond the thyroid capsule and to assess nodal metastases or tumor recurrence. The main application of US in parathyroid diseases is represented by primary hyperparathyroidism. In this condition, US plays a role after biochemical diagnosis, and it should always be strictly performed for localization purposes. In both thyroidal and parathyroid diseases, US is recommended as a guide in FNA biopsies.

  7. A role for magnesium in neonatal parathyroid gland function

    SciTech Connect

    Loughead, J.L.; Mimouni, F.; Tsang, R.C.; Khoury, J.C. )

    1991-04-01

    Little is known of the factors regulating parathyroid function in the neonatal period. Twenty-seven term infants born after uncomplicated pregnancies, labors, and deliveries were studied to test the hypothesis that in normal newborns the amplitude of parathyroid hormone (PTH) response to decreasing serum ionized calcium (iCa) correlates with serum magnesium (Mg) concentrations. Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age. Repeated measures analysis of covariance showed decreasing serum iCa (p less than 0.01) and increasing serum Mg (p less than 0.01) and PTH (p less than 0.01) over time. The change in PTH over the first 24 hours was directly correlated with cord blood (r = 0.38, p less than 0.05) and 24-hr Mg concentrations (r = 0.53, p less than 0.01). We conclude that the ability of the parathyroid gland to respond to decreasing serum iCa after birth is directly related to Mg status. We speculate that neonatal hypomagnesemia may lead to a blunted PTH secretory response, thus contributing to early neonatal hypocalcemia.

  8. Lithium stimulates the release of human parathyroid hormone in vitro.

    PubMed

    Birnbaum, J; Klandorf, H; Giuliano, A; Van Herle, A

    1988-06-01

    The effect of lithium on PTH release from human parathyroid tissue was studied using a perifusion system and an immunoradiometric assay for intact human PTH. Tissue was obtained from three patients undergoing surgery for thyroid disease, three patients with secondary hyperparathyroidism due to chronic renal insufficiency, and four patients with primary hyperparathyroidism due to a parathyroid adenoma. Addition of lithium in concentrations equivalent to the therapeutic serum levels normally attained in man (1.3 mmol/L) resulted in a significant (P less than 0.05) increase in PTH release under normocalcemic (1.15 mmol/L) conditions from normal and hyperplastic tissues. The magnitude of the lithium-induced response of PTH release ranged from a 1.4- to 5.3-fold increase above basal levels (perifusion with 1.15 mmol/L calcium alone) and was comparable to the response during a low calcium (0.42 mmol/L) perifusion. Although the response to lithium was delayed compared to that of hypocalcemia, PTH returned to basal levels immediately after removal of either stimulator. In contrast, parathyroid adenomas did not respond to either lithium or hypocalcemia in a characteristic manner, but, rather, functioned in an autonomous fashion with repeated pulsatile bursts of PTH release that were not suppressible even under hypercalcemic (1.70 mmol/L) conditions. These in vitro studies suggest that lithium therapy may elevate serum PTH levels in some patients and could, thus, be responsible for hypercalcemia in them.

  9. PSYCHOLOGICAL AND PSYCHOSOCIAL DETERMINANTS OF MUSCULOSKELETAL PAIN AND ASSOCIATED DISABILITY

    PubMed Central

    Vargas-Prada, Sergio; Coggon, David

    2015-01-01

    Although much attention has been given to the physical determinants of common musculoskeletal complaints such as back and arm pain, research points to a stronger influence of psychological factors. Multiple studies have implicated poor mental health and somatisation (a tendency to worry about common somatic symptoms) in the incidence and chronicity of musculoskeletal pain and associated disability. Also important are adverse beliefs about the prognosis of such disorders, and about the role of physical activity in their development and persistence. Differences in societal beliefs may have contributed to major variation in the prevalence of disabling musculoskeletal pain that has been observed between countries and in the same countries over time. Psychosocial aspects of work have also been linked with musculoskeletal pain, although relative risks have generally been smaller. There is a need to take account of psychological factors in the clinical management of patients with back, neck and arm pain. PMID:26612236

  10. Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs.

    PubMed

    Liles, Sofija R; Linder, Keith E; Cain, Brandon; Pease, Anthony P

    2010-01-01

    The purpose of this study is to characterize the sonographic appearance of canine parathyroid glands using high-resolution ultrasonography. Ten cadaver dogs were studied after euthanasia for reasons not relating to the parathyroid. The cervical region was examined using a 13-5 MHz linear transducer in right and left recumbency. Ultrasonographic features of the parathyroid and thyroid glands were compared with the gross and histopathologic findings. Thirty-five structures were identified sonographically as parathyroid glands but only 26 of 35 glands (74% positive predictive value) were proven to be normal parathyroid glands histopathologically. Of the nine false positives, five (14%) were proven to be lobular thyroid tissue. The remaining four (11%) structures were visible grossly or found histopathologically. There were no statistical differences between ultrasonographic and gross measurements of the parathyroid glands. The average size as seen sonographically was 3.3 x 2.2 x 1.7 mm and the average gross size was 3.7 x 2.6 x 1.6 mm (length, width, height). The average size of the thyroid lobules assessed sonographically was 2.3 x1.6 x 0.8 mm (length, width, height). Normal parathyroid glands can be identified using high-resolution ultrasonography. But some thyroid lobules will be misinterpreted as parathyroid glands; this will result in false positives when identifying parathyroid glands with ultrasonography.

  11. [A combination of diseases of the thyroid and asymptomatic adenoma of the parathyroid glands].

    PubMed

    Romanchishen, A F; Matveeva, Z S

    2006-01-01

    The authors have analyzed the cases of diagnosis of asymptomatic tumors of the parathyroid gland made during 8814 operations on the thyroid in the period from 1995 through 2004. The probability of detecting parathyroid incidentalomas in different forms of goiter was calculated which reaches 0.4%. A precision technique of operating allows the parathyroid tumors to be detected at the preclinical stage in all patients apart from a removal of the necessary volume of the thyroid tissue, guaranteed preservation of the laryngeal nerves and parathyroid glands.

  12. Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos.

    PubMed

    Neves, Hélia; Dupin, Elisabeth; Parreira, Leonor; Le Douarin, Nicole M

    2012-01-15

    Epithelial-mesenchymal interactions are crucial for the development of the endoderm of the pharyngeal pouches into the epithelia of thymus and parathyroid glands. Here we investigated the dynamics of epithelial-mesenchymal interactions that take place at the earliest stages of thymic and parathyroid organogenesis using the quail-chick model together with a co-culture system capable of reproducing these early events in vitro. The presumptive territories of thymus and parathyroid epithelia were identified in three-dimensionally preserved pharyngeal endoderm of embryonic day 4.5 chick embryos on the basis of the expression of Foxn1 and Gcm2, respectively: the thymic rudiment is located in the dorsal domain of the third and fourth pouches, while the parathyroid rudiment occupies a more medial/anterior pouch domain. Using in vitro quail-chick tissue associations combined with in ovo transplantations, we show that the somatopleural but not the limb bud mesenchyme, can mimic the role of neural crest-derived pharyngeal mesenchyme to sustain development of these glands up to terminal differentiation. Furthermore, mesenchymal-derived Bmp4 appears to be essential to promote early stages of endoderm development during a short window of time, irrespective of the mesenchymal source. In vivo studies using the quail-chick system and implantation of growth factor soaked-beads further showed that expression of Bmp4 by the mesenchyme is necessary during a 24 h-period of time. After this period however, Bmp4 is no longer required and another signalling factor produced by the mesenchyme, Fgf10, influences later differentiation of the pouch endoderm. These results show that morphological development and cell differentiation of thymus and parathyroid epithelia require a succession of signals emanating from the associated mesenchyme, among which Bmp4 plays a pivotal role for triggering thymic epithelium specification.

  13. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias.

    PubMed

    Gill, Anthony J; Clarkson, Adele; Gimm, Oliver; Keil, Juliane; Dralle, Henning; Howell, Viive M; Marsh, Deborah J

    2006-09-01

    Parathyroid carcinoma is notoriously difficult to diagnose with confidence in borderline cases. Commonly there is a long lag time between diagnosis and clinical evidence of malignant behavior even in histopathologically straightforward lesions. There is therefore a need for a novel adjunctive marker to assist in the diagnosis of carcinoma. Parafibromin is the protein encoded by the putative tumor suppressor gene HRPT2. Mutations predicted to inactivate parafibromin were first detected in the germline of patients with hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Subsequently, somatic mutations have been identified in the majority of sporadic carcinomas. We performed immunohistochemistry for parafibromin on 115 parathyroid tissues comprising 4 HPT-JT-related tumors (3 adenomas and 1 carcinoma), 11 sporadic parathyroid carcinomas, 79 sporadic adenomas, 3 multiple endocrine neoplasia 2A-related adenomas, 2 sporadic primary hyperplasias, 2 multiple endocrine neoplasia (MEN)-1-related hyperplasias, 6 secondary hyperplasias, 4 tertiary hyperplasias, and 4 normal parathyroid glands. There was complete absence of nuclear staining in 3 of 4 (75%) HPT-JT-related tumors and 8 of 11 (73%) sporadic parathyroid carcinomas and focal weak staining in 1 of 4 HPT-JT tumors and 2 of 11 sporadic parathyroid carcinomas. Only 1 parathyroid carcinoma exhibited diffuse strong nuclear expression of parafibromin. In contrast, 98 of 100 non-HPT-JT-related benign parathyroids showed diffuse strong nuclear positivity and 2 of 100 showed weak positive staining. We conclude that, in the correct clinical and pathologic context, complete absence of nuclear staining for parafibromin is diagnostic of parathyroid carcinoma or an HPT-JT-related tumor.

  14. Calcification of all four parathyroid glands in a hemodialysis patient with secondary hyperparathyroidism revealed by computerized tomography.

    PubMed

    Peces, R; Rodríguez, M; González, F; Ablanedo, P

    2001-09-01

    This report describes the parathyroid scan, computerized tomography and histologic findings in a young female hemodialysis patient with severe secondary hyperparathyroidism. These findings included hyperplasia and calcification of all four parathyroid glands.

  15. Role of paraoxonase-1 in bone anabolic effects of parathyroid hormone in hyperlipidemic mice

    SciTech Connect

    Lu, Jinxiu; Cheng, Henry; Atti, Elisa; Shih, Diana M.; Demer, Linda L.; Tintut, Yin

    2013-02-01

    Highlights: ► Anabolic effects of PTH were tested in hyperlipidemic mice overexpressing PON1. ► Expression of antioxidant regulatory genes was induced in PON1 overexpression. ► Bone resorptive activity was reduced in PON1 overexpressing hyperlipidemic mice. ► PON1 restored responsiveness to intermittent PTH in bones of hyperlipidemic mice. -- Abstract: Hyperlipidemia blunts anabolic effects of intermittent parathyroid hormone (PTH) on cortical bone, and the responsiveness to PTH are restored in part by oral administration of the antioxidant ApoA-I mimetic peptide, D-4F. To evaluate the mechanism of this rescue, hyperlipidemic mice overexpressing the high-density lipoprotein-associated antioxidant enzyme, paraoxonase 1 (Ldlr{sup −/−}PON1{sup tg}) were generated, and daily PTH injections were administered to Ldlr{sup −/−}PON1{sup tg} and to littermate Ldlr{sup −/−} mice. Expression of bone regulatory genes was determined by realtime RT-qPCR, and cortical bone parameters of the femoral bones by micro-computed tomographic analyses. PTH-treated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTH receptor (PTH1R), activating transcription factor-4 (ATF4), and osteoprotegerin (OPG) in femoral cortical bone, as well as significantly greater cortical bone mineral content, thickness, and area in femoral diaphyses compared with untreated Ldlr{sup −/−}PON1{sup tg} mice. In contrast, in control mice (Ldlr{sup −/−}) without PON1 overexpression, PTH treatment did not induce these markers. Calvarial bone of PTH-treated Ldlr{sup −/−}PON1{sup tg} mice also had significantly greater expression of osteoblastic differentiation marker genes as well as BMP-2-target and Wnt-target genes. Untreated Ldlr{sup −/−}PON1{sup tg} mice had significantly greater expression of PTHR1 than untreated Ldlr{sup −/−} mice, whereas sclerostin expression was reduced. In femoral cortical bones, expression levels of transcription factors, Fox

  16. Microbiome impact on metabolism and function of sex, thyroid, growth and parathyroid hormones.

    PubMed

    Kunc, Michał; Gabrych, Anna; Witkowski, Jacek M

    2016-01-01

    Commensal bacteria and their genes associated with host are known as microbiome. In recent years, microbial influence on host endocrine system has been under detailed investigation. The role of microbiome in the pathogenesis of insulin resistance and obesity, the function of hypothalamic-pituitary-adrenal axis and secretion of hormones regulating appetite is well described in world literature. In this article we discuss poorly reviewed issues: the microbiome role in modulation of non-peptide (sex and thyroid) and peptide (growth hormone and parathyroid hormone) functions. Understanding complex bidirectional relations between host endocrine system and bacteria is of fundamental importance to understanding microbial impact on host reproduction, risk of endocrine-related cancers, pathogenesis of non-thyroidal illness syndrome, growth failure in children and hormonal changes during chronic kidney disease. This article also highlights effects of dietary compounds on microbiome composition and bacterial enzymes activity, and thus host hormonal status.

  17. The effects of cinacalcet treatment on bone mineral metabolism, anemia parameters, left ventricular mass index and parathyroid gland volume in hemodialysis patients with severe secondary hyperparathyroidism.

    PubMed

    Torun, Dilek; Yildiz, Ismail; Micozkadioglu, Hasan; Nursal, Gul Nihal; Yigit, Fatma; Ozelsancak, Ruya

    2016-01-01

    The aim of this study was to investigate the effects of cinacalcet therapy on anemia parameters, bone mineral metabolism, left ventricular mass index (LVMI) and parathyroid gland volume in hemodialysis (HD) patients with secondary hyperparathyroidism. Twenty-five HD patients (M/F: 11/14, mean age: 45.2±17.9 years, mean HD duration: 96.4±32.7 months) were included in this prospective pilot study. The indication to start calcimimetic therapy was persistent serum levels of parathyroid hormone (PTH)>1000 pg/mL, refractory to intravenous (i.v.) vitamin D and phosphate-binding therapy. The initial and one-year results of adjusted serum calcium (Ca+2), phosphate (P), Ca×P product, PTH, hemoglobin (Hb) and ferritin levels, transferrin saturation index (TSAT), median weekly erythropoietin (EPO) dose, LVMI, and parathyroid volume by parathyroid ultrasonography were determined. There were no differences between pre- and post-treatment levels of serum Ca+2 (P=0.853), P (P=0.447), Ca×P product (P=0.587), PTH (P=0.273), ferritin (P=0.153) and TSAT (P=0.104). After 1 year of calcimimetic therapy, the Hb levels were significantly higher than the initial levels (P=0.048). The weekly dose of EPO decreased with no statistical significance. The dose of cinacalcet was increased from 32.4±12.0 to 60.0±24.4 mg/day (P=0.01). There were no differences between the pre- and post-treatment results regarding weekly vitamin D dose, parenteral iron dose, LVMI and parathyroid volume. The results of our study suggest that cinacalcet therapy might have an additional benefit in the control anemia in HD patients.

  18. Sleeping Parathyroid Tumor: Rapid Hyperfunction after Removal of the Dominant Tumor

    PubMed Central

    Simonds, William F.; Weinstein, Lee S.; Collins, Michael T.; Kebebew, Electron; Nilubol, Naris; Phan, Giao Q.; Libutti, Steven K.; Remaley, Alan T.; Van Deventer, Manuel; Marx, Stephen J.

    2012-01-01

    Context: Due to frequent multiplicity of tumors in multiple endocrine neoplasia type 1, it may be difficult to decide when to stop a parathyroid exploration. A fall of intraoperative serum PTH by a certain percentage during parathyroid surgery is often used as one criterion for ending the operation. Results: We report two patients with primary hyperparathyroidism due to multiple endocrine neoplasia type 1 who had their first parathyroidectomy at the National Institutes of Health. In both cases, two and a half glands were removed, an extensive search was done for an occult parathyroid tumor, and intraoperative PTH decreased markedly to the lower limits of normal, suggesting a successful operation. Despite this, both patients became hypercalcemic within 3 d after the operation and showed persistent primary hyperparathyroidism. Detailed findings suggest the following course: chronic hypercalcemia had caused near total suppression of PTH secretion by an undiscovered parathyroid tumor (sleeping parathyroid tumor). When the hypercalcemia decreased after surgery due to the removal of the dominant parathyroid tumor(s), the abnormal yet previously suppressed tumor rapidly began to oversecrete PTH and thus caused postoperative hypercalcemia. Conclusions: Even a fall of the intraoperative PTH to the lower limits of the normal range cannot guarantee that removal of all parathyroid tumors has been complete in cases with multiple tumors. These findings likely reflect strikingly differing PTH secretory functions among distinct tumors in the same patient, with hypercalcemia at least from a dominant tumor suppressing PTH secretion by one or more other parathyroid tumors. PMID:22508712

  19. Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Schnoes, Heinrich K.; Deluca, Hector F.; Phelps, Mary E.; Klein, Robert F.

    1988-01-01

    The effect of an 8-day space flight (Spacelab mission 2) on plasma levels of the vitamin D and parathyroid hormones is investigated experimentally in four crew members. The results are presented in tables and graphs and briefly characterized. Parathyroid hormone levels remained normal throughout the flight, whereas vitamin D hormone levels increased significantly on day 1 but returned to normal by day 7.

  20. Parathyroid scintigraphy, histopathology correlation in patients with tropical pancreatitis and coexisting primary hyperparathyroidism

    PubMed Central

    Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga

    2013-01-01

    Purpose: Tropical pancreatitis (TP) is a juvenile, non-alcoholic type of chronic pancreatitis and is highly prevalent in Kerala, India. Increasing prevalence of TP and its varied manifestations prompted us to undertake this retrospective analysis. We attempted to study the incidence of TP in patients with primary hyperparathyroidism (PHPT) and correlate with calcium levels, scintigraphy and histopathology findings. Materials and Methods: Records of 44 hypercalcemic patients with raised parathormone (PTH) were analyzed. Clinical, biochemical and imaging findings were noted to look for diabetes mellitus and pancreatitis. All patients underwent dual phase 99m Technetium methoxy isobutyl isonitrile parathyroid scintigraphy in our department between January 2007 and 2010. Gamma probe assisted minimally invasive parathyroidectomy was performed. Histopathological correlation was obtained in all patients. Results: Our study shows 18% (8/44 patients) incidence of TP in patients with PHPT (compared to 7% reported in 1970's) in Kerala. Results show involvement of middle aged, non-alcoholic males. No direct association between severity of diabetes, pancreatitis and PHPT was noted in our series. Parathyroid adenoma was the most common underlying pathology. All TP patients’ clinical outcome improved post parathyroidectomy. TP patients with PHPT demonstrated adenomas, mainly composed of oxyphilic cells. Non pancreatitis group interestingly showed a varied picture of adenoma, hyperplasia with predominance of chief cells histologically. Conclusion: There is a 2.6 fold increase in the incidence of TP (18%) in patients with PHPT. Hypercalcemia may be the causative factor leading to TP in PHPT patients in our limited series. The data suggests a causal association between pancreatitis and PHPT. Patients presenting with either one or a combination of hypercalcemia, pancreatic dysfunction or raised PTH need to be thoroughly evaluated as their management is interlinked. PMID:24019667

  1. Postprandial parathyroid hormone response to four calcium-rich foodstuffs.

    PubMed

    Kärkkäinen, M U; Wiersma, J W; Lamberg-Allardt, C J

    1997-06-01

    We studied the effects of four calcium-rich foodstuffs on postprandial parathyroid hormone secretion. Four hundred milligrams calcium from either Emmental cheese, milk, sesame seeds, spinach, or calcium salt (calcium lactate gluconate + calcium carbonate) or no additional calcium (control session) were given to nine female volunteers immediately after a first blood sample (at 0900) in random order with a light standardized meal containing 37 mg Ca. Blood samples were taken at 0900 (before the calcium load), 1000, 1100, 1300, and 1500 at every study session. Urine was collected during the sessions. Serum ionized calcium, phosphate, magnesium, intact parathyroid hormone, and urinary calcium excretion were measured. The serum ionized calcium concentration increased significantly after ingesting cheese (P = 0.004, contrast analysis) or calcium salt (P = 0.05, contrast analysis) compared with the control session. Compared with the control session, the serum phosphate concentration increased after the cheese session (P = 0.004, contrast analysis) and after the milk session (P = 0.02, contrast analysis). Calcium salt (P = 0.007, contrast analysis) and cheese (P = 0.002, contrast analysis) caused a significant decline in serum intact parathyroid hormone compared with the control session. The urinary calcium excretion with cheese was 141% (P = 0.001), with milk was 107% (P = 0.004), and with calcium salt was 75% (P = 0.02) above that of the control session. Our results show that calcium from sesame seeds and spinach does not cause an acute response in calcium metabolism. Our results indicate that fermented cheese could be a better dietary source of calcium than milk when the metabolic effects of the foodstuffs are considered.

  2. A Rare Constellation of Hürthle Cell Thyroid Carcinoma and Parathyroid Carcinoma.

    PubMed

    Zakerkish, Mehrnoosh; Rajaei, Elham; Dargahi, Mehrdad; Bahadoram, Mohammad

    2015-12-01

    Separate occurrence of thyroid and parathyroid carcinoma in patients is extremely rare, and to the best of our knowledge, only 7 patients with documented parathyroid and papillary thyroid carcinomas have been described formerly in published reports. We report a patient with an extremely unusual clinical presentation of Hürthle cell carcinoma in thyroid and parathyroid carcinoma. The patient displayed a rare presentation of life-threatening hypercalcaemia after total para-thyroidectomy and failed to respond to standard therapy. Our review of available literature yielded insufficient evidence in managing such. When a patient with thyroid cancer is diagnosed, checking for serum calcium is advised. This is considered a useful method for detecting possible incidental parathyroid lesion and screening the probable concealed parathyroid pathology.

  3. Quantitative autoradiography of parathyroid glands in rats with carbon-14-labeled amino acids

    SciTech Connect

    Wortman, J.A.; Alavi, A.; Attie, M.; Yudd, A.P.; Johnston, S.A.; Greenberg, J.

    1987-09-01

    We have utilized a quantitative autoradiographic method as a means of evaluating amino acid uptake of the rat parathyroid gland for the ultimate purpose of finding agents potentially suitable for position emission tomographic scanning of parathyroid glands. L-(1-/sup 14/C)leucine and L-(guanido-/sup 14/C)arginine were evaluated because of their relatively high content in the synthetic products of the parathyroid glands compared with other neck tissues, thyroid gland, and muscle. Carbon-14 leucine disappeared rapidly from plasma following intravenous injection and there was relatively selective uptake of the (/sup 14/C)leucine and (/sup 14/C)arginine by the parathyroid glands when compared with uptake by the thyroid gland and neck muscle. These data suggest that both agents warrant further investigation for their potential utility in positron emission tomographic scanning of the parathyroid gland.

  4. Determination of reversible protein equilibrium association coefficients using light scattering

    NASA Astrophysics Data System (ADS)

    Larkin, Michael

    2009-03-01

    The characterization in solution of reversible protein associations as well as associations between proteins and small molecules is essential in many areas of science. Understanding cellular function or developing and formulating pharmaceuticals or other biologically active materials often requires quantitation of such associations. Most pharmaceuticals have functionality due solely to association with molecules within the body, and the discovery and accurate characterization of these associations is a key element for pharmaceutical development. Unfortunately, most methods used to measure associations of proteins require either immobilizing the protein on a surface (e.g. surface plasmon resonance), which potentially alters the protein characteristics, or require considerable time and effort and large quantities of sample (e.g. analytical ultracentrifugation, isothermal titration calorimetry). Light scattering based measurements of reversible association coefficients require much less sample and may be performed much more rapidly than other free solution techniques. In this talk I describe how static and dynamic light scattering may each independently be used to measure equilibrium association coefficients between proteins in free solution, and may also be used to observe and quantitate the association of small molecules with them. I present background theory for both static and dynamic light scattering measurements of equilibrium associations, and examples of measurements made of both model systems and of systems with commercial relevance in the pharmaceutical industry.

  5. The Significance of Ultrasound in Determining Whether SHPT Patients Are Sensitive to Calcitriol Treatment.

    PubMed

    Liang, Xing-xin; Li, Fan; Gao, Feng; Li, Chun-xiao; Qiao, Xiao-hui; Zhang, Jia-jie; Du, Lian-fang

    2016-01-01

    This study was to explore the significance of ultrasound in determining whether the patients with secondary hyperparathyroidism (SHPT) are sensitive to calcitriol treatment. According to the decrease value of parathyroid hormone (PTH), 42 SHPT patients were divided into two groups: drug susceptible group and drug insusceptible group. These 42 SHPT patients' ultrasound images were retrospectively analyzed. The morphology, size, number, blood flow, elastic modulus, and perfusion of the parathyroid glands were correlated with drug therapeutic outcome (oral calcitriol). Most SHPT patients with drug susceptible showed volume <438.50 mm(3) and number ≤2, with 0-1 structural and vascular patterns, associated with Relative Maximum Intensity (RIMAX) <1.59 and elastic modulus <18.8 kPa, whereas most SHPT patients with drug insusceptible showed volume ≥438.50 mm(3) and number ≥3, with 2-3 structural and vascular patterns, associated with Relative Maximum Intensity (RIMAX) ≥1.59 and elastic modulus ≥18.8 kPa. Therefore, ultrasonography in SHPT allows an accurate definition of the morphology, size, number, blood flow, elastic modulus, and perfusion of the parathyroid glands and is useful in determining whether SHPT patients are sensitive to calcitriol treatment.

  6. Observations on the effect of parathyroid hormone on environmental blood lead concentrations in humans

    SciTech Connect

    Osterloh, J.D. )

    1991-02-01

    The effect of parathyroid hormone (PTH) on blood lead (Pb) concentrations was observed preliminarily in three different situations. Of 342 healthy bus drivers with no unusual exposure to Pb, 25 drivers with the highest and 25 with the lowest blood Pb were compared for serum PTH concentrations. There was no association between blood Pb and serum PTH concentrations. Eight women with postmenopausal osteoporosis enrolled in an experimental protocol to increase bone mass received daily PTH (1-34 fragment) for 1 week, calcitonin for the next 2 weeks, and oral calcium for the subsequent 10 weeks. This cycle was repeated four times during the year. Initial blood Pb concentrations averaged 6.0 micrograms/dl (range 2.1-8.9). Mean blood Pb concentrations decreased by 1.7 micrograms/dl over 1 year of therapy. The confidence interval for this change excluded zero, the mean change was significantly different from the mean change for comparative population (P less than 0.050), and paired changes were statistically significant (P = 0.045). Lastly, a single subject with hyperparathyroid disease and no unusual exposures to lead demonstrated stabilized blood Pb concentrations that were 50% lower after removal of his hyperplastic parathyroid glands. These observations suggest that the effect of PTH on increasing bone turnover and releasing Pb into blood is not easily detected at low physiologic amounts of PTH, but that with pathologic increases of PTH in hyperparathyroid disease, elevation of blood Pb from bone or increased gastrointestinal absorption may be possible. Likewise, either bone building therapies (PTH + calcitonin + calcium) may move Pb from blood into bone or supplemental calcium may decrease Pb gastrointestinal absorption, thereby explaining the observed lower blood Pb concentrations.

  7. Disturbances of parathyroid hormone–vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study

    PubMed Central

    Miroliaee, Arash; Nasiri-Toosi, Mohsen; Esteghamati, Alireza; Abdollahi, Alireza; Mazloumi, Mehdi

    2010-01-01

    Purpose Liver has an important role in metabolism of vitamin D. This study aimed to evaluate the patterns of vitamin D–parathyroid hormone (PTH) disturbance and correlate it in patients with non-cholestatic chronic liver disease (CLD). Methods A total of 40 healthy controls and 90 consecutive patients with evidence of non-cholestatic CLD due to hepatitis C (n = 28), hepatitis B (n = 26), autoimmune hepatitis (n = 19), and cryptogenic causes (n = 17) were enrolled. Cirrhosis was evident in 51 patients. Serum concentrations of 25-hydroxy vitamin D, PTH, calcium, phosphate, and liver enzymes were measured. Child–Pugh classification was determined in cirrhotic patients. Results Vitamin D deficiency (<50 nmol/l) was found in 46 (51.1%) patients and vitamin D insufficiency (50–80 nmol/l) in 15 (16.7%) patients. Secondary hyperparathyroidism (serum PTH > 6.8 pmol/l) was present in 6 (6.7%) patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic versus noncirrhotic patients (76.5 vs. 17.9%; P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. Child–Pugh class B and C patients had significantly lower vitamin D level compared with class A patients (P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. No significant correlation was seen between vitamin D and PTH, calcium or phosphate levels. Lower serum level of vitamin D was associated with coagulopathy, hyperbilirubinemia, hypoalbuminemia, anemia, and thrombocytopenia. Conclusions Vitamin D inadequacy and the severity of liver dysfunction move in parallel in patients with non-cholestatic CLD. Vitamin D assessment and replacement should be considered in the management of patients with non-cholestatic CLD. PMID:21063488

  8. Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.

    PubMed

    Wang, Hua; Liu, Jingning; Yin, Ying; Wu, Jun; Wang, Zilu; Miao, Dengshun; Sun, Wen

    2014-01-01

    Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP) is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP) 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX) to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo.

  9. Role of protein kinase C on the acute desensitization of renal cortical adenylate cyclase to parathyroid hormone.

    PubMed

    Bellorin-Font, E; López, C; Díaz, K; Pernalete, N; López, M; Starosta, R

    1995-01-01

    The mechanisms of adenylate cyclase desensitization to parathyroid hormone are still unclear. Current evidence suggest that the signal generated after PTH binding to receptors results in activation of adenylate cyclase and stimulation of phospholipase C with subsequent activation of protein kinase C. Recent studies have suggested a role of protein kinase C on the regulation of the PTH-dependent receptor-adenylate cyclase system in cultured cells. Therefore, the present studies were conducted to examine the role of protein kinase C on the desensitization of canine renal cortical adenylate cyclase after an acute exposure in vivo to PTH. A group of normal dogs were treated with a single intravenous injection of 1 microgram/k of syn bPTH (1-34) or Nle bPTH (3-34). Ten minutes later, animals were subjected to bilateral nephrectomy and the kidney cortex processed for preparations of basolateral membranes for determinations of adenylate cyclase activity, as well as membrane and cytosolic fractions for analysis of protein kinase C activity. Animals not treated with PTH were used as controls. PTH administration in vivo resulted in a 46.9 +/- 9.3% decrease in maximal adenylate cyclase activity in vitro in response to syn bPTH (1-34) (P < 0.001). Likewise, PTH binding as measured with 125I-Nle8,18,Tyr34-bPTH (1-34)NH2 showed a 40 +/- 3% decrease. This alterations were associated with a marked translocation of protein kinase C from the cytosol to the membrane. Thus, protein kinase C activity in membrane fractions increased from 160.6 +/- 44.8 pmol Pi/min in controls to 500.4 +/- 123 in PTH treated dogs (P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines.

    PubMed

    Messier, A A; Heyder, E; Braithwaite, W R; McCluggage, C; Peck, A; Schaefer, K E

    1979-01-01

    Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

  11. Parathyroid hormone/parathyroid hormone-related peptide regulate osteosarcoma cell functions: Focus on the extracellular matrix (Review)

    PubMed Central

    Nikitovic, Dragana; Kavasi, Rafaela-Maria; Berdiaki, Aikaterini; Papachristou, Dionysios J.; Tsiaoussis, John; Spandidos, Demetrios A.; Tsatsakis, Aristides M.; Tzanakakis, George N.

    2016-01-01

    Osteosarcoma (OS) is a primary bone tumor of mesenchymal origin mostly affecting children and adolescents. The OS extracellular matrix (ECM) is extensively altered as compared to physiological bone tissue. Indeed, the main characteristic of the most common osteoblastic subtype of OS is non-mineralized osteoid production. Parathyroid hormone (PTH) is a polypeptide hormone secreted by the chief cells of the parathyroid glands. The PTH-related peptide (PTHrP) may be comprised of 139, 141 or 173 amino acids and exhibits considerate N-terminal amino acid sequence homology with PTH. The function of PTH/PTHrP is executed through the activation of the PTH receptor 1 (PTHR1) and respective downstream intracellular pathways which regulate skeletal development, bone turnover and mineral ion homeostasis. Both PTHR1 and its PTH/PTHrP ligands have been shown to be expressed in OS and to affect the functions of these tumor cells. This review aims to highlight the less well known aspects of PTH/PTHrP functions in the progression of OS by focusing on ECM-dependent signaling. PMID:27499459

  12. Assessment of parathyroid glands in hemodialysis patients by using color Doppler sonography.

    PubMed

    Ozcan, Umit Aksoy; Oktay, Ilay

    2009-11-01

    The aim of this study was to assess the role of color and spectral Doppler ultrasound (CDU) in the evaluation of enlarged parathyroid glands in hemodialysis patients with secondary hyperparathyroidism. Fourteen hemodialysis patients with elevated intact parathyroid hormone (iPTH) levels were evaluated prospectively with CDU. The volume of each observed parathyroid gland and the spectral CDU data (velocities, resistance and pulsatility indices, systolic to diastolic ratio, and flow volume output (FVO)) were noted. The biochemical data (iPTH, calcium, phosphate levels), and CDU results were analyzed with the Spearman correlation test. Two patients were excluded, and 27 enlarged parathyroid glands were observed in 12 patients. The mean total volume of enlarged parathyroid glands per patient was 1.95 cm(3) (0.06-5.5 cm(3)). Arterial supply was demonstrated in 78% (21/27) of enlarged parathyroid glands. Mean total FVO of enlarged glands per patient was 238.5 ml/min (620-0 ml/min) and mean iPTH level was 1,477 pg/ml (643-3,132 pg/ml). The positive correlations of total volume (p = 0.022), iPTH (p = 0.024), and FVO (p = 0.022) were statistically significant. In secondary hyperparathyroidism, total volume of the visualized enlarged parathyroid glands and the total of FVOs per patient are positively correlated with iPTH levels which may help clinical management and follow-up of end-stage renal disease patients.

  13. Location, number and morphology of parathyroid glands: results from a large anatomical series.

    PubMed

    Lappas, Dimitrios; Noussios, George; Anagnostis, Panagiotis; Adamidou, Fotini; Chatzigeorgiou, Antonios; Skandalakis, Panagiotis

    2012-09-01

    Surgical management of parathyroid gland disease may sometimes be difficult, due mainly to the surgeon's failure to successfully detect parathyroids in unusual locations. The records of 942 cadavers (574 men and 368 women) who underwent autopsy in the Department of Forensic Medicine in Athens during the period 1988-2009 were reviewed. In total, 3,796 parathyroid glands were resected and histologically verified. Parathyroid glands varied in number. In 47 cases (5 %), one supernumerary (fifth) parathyroid was found, while in 19 cases (2 %) three parathyroid glands found. Superior glands were larger than inferior ones. However, there was no significant difference between the genders with respect to gland size. In 324 (8.5 %) out of 3,796, the glands were detected in an ectopic location: 7 (0.2 %) in the thyroid parenchyma, 79 (2 %) in different sites in the neck and 238 (6.3 %) in the mediastinum, 152 (4.1 %) of which were found in the upper and 86 (2.2 %) in the lower mediastinum. Significant anatomical variations of normal parathyroid glands may exist regarding number and location-knowledge that is essential for their successful identification and surgical management.

  14. Quantitative and three-dimensional aspects of the rat parathyroid gland in normo-, hypo-, and hypercalcemia.

    PubMed

    Wernerson, A; Svensson, O; Reinholt, F P

    1995-10-01

    The ultrastructure of the rat parathyroid has been under study for more than 35 years, but controversies still exist, especially regarding structure-function relationships. The present review focuses on recent morphological parathyroid research on rats under normal conditions and in various states of disturbed calcium metabolism. To facilitate discussions on functional aspects, current biochemical data, particularly those dealing with the regulation of parathyroid hormone synthesis and release, are also considered. Our results from quantitative studies and from investigations employing serial sectioning form the basis for the discussions. A central issue is whether the parathyroid secretory cells undergo secretory cycles. Prompted by results obtained from improved fixation procedures and serial sectioning, we question the basis for the theory of secretory cycles. Since the rat parathyroid secretory cell is polar, a single section is not an appropriate sample for estimating functional activity and for comparing the structure and distribution of intracellular components of adjacent cells. The heterogeneity in ultrastructural appearance of intracellular vesicles calls for the use of specific markers in relating the structure of the vesicular compartment to intracellular processing of hormone. The importance of unbiased quantitative techniques is illustrated in discussions on cell number and size for estimating the response of the parathyroid gland to different functional states or disorders demanding changes in secretion of parathyroid hormone, e.g., hyper- and hypocalcemia.

  15. Endogenous parathyroid hormone-related protein compensates for the absence of parathyroid hormone in promoting bone accrual in vivo in a model of bone marrow ablation.

    PubMed

    Zhu, Qi; Zhou, Xichao; Zhu, Min; Wang, Qian; Goltzman, David; Karaplis, Andrew; Miao, Dengshun

    2013-09-01

    To assess the effect of hypoparathyroidism on osteogenesis and bone turnover in vivo, bone marrow ablation (BMXs) were performed in tibias of 8-week-old wild-type and parathyroid hormone-null (PTH(-/-)) mice and newly formed bone tissue was analyzed from 5 days to 3 weeks after BMX. At 1 week after BMX, trabecular bone volume, osteoblast numbers, alkaline phosphatase-positive areas, type I collagen-positive areas, PTH receptor-positive areas, calcium sensing receptor-positive areas, and expression of bone formation-related genes were all decreased significantly in the diaphyseal regions of bones of PTH(-/-) mice compared to wild-type mice. In contrast, by 2 weeks after BMX, all parameters related to osteoblastic bone accrual were increased significantly in PTH(-/-) mice. At 5 days after BMX, active tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts had appeared in wild-type mice but were undetectable in PTH(-/-) mice, Both the ratio of mRNA levels of receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) and TRAP-positive osteoclast surface were still reduced in PTH(-/-) mice at 1 week but were increased by 2 weeks after BMX. The expression levels of parathyroid hormone-related protein (PTHrP) at both mRNA and protein levels were upregulated significantly at 1 week and more dramatically at 2 weeks after BMX in PTH(-/-) mice. To determine whether the increased newly formed bones in PTH(-/-) mice at 2 weeks after BMX resulted from the compensatory action of PTHrP, PTH(-/-) PTHrP(+/-) mice were generated and newly formed bone tissue was compared in these mice with PTH(-/-) and wild-type mice at 2 weeks after BMX. All parameters related to osteoblastic bone formation and osteoclastic bone resorption were reduced significantly in PTH(-/-) PTHrP(+/-) mice compared to PTH(-/-) mice. These results demonstrate that PTH deficiency itself impairs osteogenesis, osteoclastogenesis, and osteoclastic bone resorption, whereas subsequent upregulation of PTHr

  16. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    SciTech Connect

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-05-15

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated (/sup 3/H)thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause.

  17. Determining Suicide Risk Using a New Word Association Technique.

    ERIC Educational Resources Information Center

    Lasaga, Jose I.; And Others

    Patients' rights legislation makes the determination of possible danger to self and others extremely important for patients about to be discharged from mental institutions, especially patients who were admitted because of suicidal behavior. Because evaluation methods which rely on patient self-reports may be manipulated by clever patients, a new…

  18. Some determinants of psychological deficits associated with chronic cannabis consumption.

    PubMed

    Soueif, M I

    1976-01-01

    The present study was done in order to investigate the following general hypothesis: "Other conditions being equal, the lower the non-drug level of proficiency on tests of cognitive and psychomotor performance the smaller the size of function deficit associated with drug taking". Twelve objective tests generating 16 test variables were administered to 850 chronic cannabis takers and 839 comparable non-takers, all males ranging in age between 15 and 50 years and representing various positions on "literacy-illiteracy" and "urbanism-ruralism". Six specific predictions were formulated; (1) Performance on the test is expected to be correlated with the level of leteracy of the subject. (2) the lower the level of literacy the smaller the size of function deficit associated with cannabis taking. (3) Performance on the tests is expected to be correlated with the level of urbanism of the subject. (4) The lower the level of urbanism (i.e. more ruralism) the smaller the size of function deficit associated with drug taking. (5) Performance on the tests is expected to correlate inversely with age. (6) The older the subject the smaller the amount of function deficit associated with cannabis consumption. All our predictions were confirmed. The consistency of these results raises the possibility that a basic regularity governing the relationship between cannabis consumption and psychological-function deficit is being uncovered. The suggestion was made that our major hypothesis might prove valid with regard to the area of acute effects of cannabis taking as well. Our hypothesis was shown to provide a broad framework capable of integrating a number of conflicting reports both in the area of long term and that of short term cannabis use.

  19. Metabolism in immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease.

    PubMed Central

    Hruska, K A; Kopelman, R; Rutherford, W E; Klahr, S; Slatopolsky, E; Greenwalt, A; Bascom, T; Markham, J

    1975-01-01

    The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism. PMID:1141439

  20. Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone

    NASA Technical Reports Server (NTRS)

    Hillsley, M. V.; Frangos, J. A.

    1996-01-01

    It is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.

  1. Parathyroid hormone induces epithelial-to-mesenchymal transition via the Wnt/β-catenin signaling pathway in human renal proximal tubular cells.

    PubMed

    Guo, Yunshan; Li, Zhen; Ding, Raohai; Li, Hongdong; Zhang, Lei; Yuan, Weijie; Wang, Yanxia

    2014-01-01

    Epithelial-to-mesenchymal transition (EMT) has been shown to play an important role in renal fibrogenesis. Recent studies suggested parathyroid hormone (PTH) could accelerate EMT and subsequent organ fibrosis. However, the precise molecular mechanisms underlying PTH-induced EMT remain unknown. The present study was to investigate whether Wnt/β-catenin signaling pathway is involved in PTH-induced EMT in human renal proximal tubular cells (HK-2 cells) and to determine the profile of gene expression associated with PTH-induced EMT. PTH could induce morphological changes and gene expression characteristic of EMT in cultured HK-2 cells. Suppressing β-catenin expression or DKK1 limited gene expression characteristic of PTH-induced EMT. Based on the PCR array analysis, PTH treatment resulted in the up-regulation of 18 genes and down-regulation of 9 genes compared with the control. The results were further supported by a western blot analysis, which showed the increased Wnt4 protein expression. Wnt4 overexpression also promotes PTH-induced EMT in HK-2 cells. The findings demonstrated that PTH-induced EMT in HK-2 cells is mediated by Wnt/β-catenin signal pathway, and Wnt4 might be a key gene during PTH-induced EMT.

  2. Contrast Agent Ultrasonography before and after HIFU Treatment of Parathyroid Glands

    NASA Astrophysics Data System (ADS)

    Kovatcheva, Roussanka; Arnaud, Françoise; Lacoste, François

    2010-03-01

    OBJECTIVES: To observe changes in the parathyroid tissue treated by extracorporeal HIFU. MATERIAL AND METHODS: 5 patients were treated for primary hyperparathyroidism by thermally ablating enlarged parathyroid glands using an external HIFU applicator. The treated glands were visualized with B-Mode and contrast enhanced ultrasonography (CEUS) before, 1 week and 4 weeks post HIFU. Serum iPTH, calcium, and phosphorus levels were monitored before and after the treatment. RESULTS: The initial results showed a correlation between contrast agent uptake of treated parathyroid tissue, the reduction of volume of the gland and the decrease of iPTH levels. CONCLUSIONS These results show it is possible to use CEUS to monitor the thermal ablation of parathyroid glands.

  3. Computed Tomography and Magnetic Resonance Imaging of the Thyroid and Parathyroid Glands.

    PubMed

    Warren Frunzac, Rebekkah; Richards, Melanie

    2016-01-01

    Computed tomography (CT) and magnetic resonance imaging (MRI) are advanced imaging modalities that are not typically utilized as part of the initial evaluation of thyroid and parathyroid pathology. However, both modalities have applications in complex cases, particularly in the reoperative setting and in operative planning for initial or recurrent carcinomas. As part of a multimodal approach, CT and MRI can increase the successful preoperative localization of abnormal parathyroid glands. Newer imaging modalities, such as PET-CT and SPECT-CT in thyroid imaging, and 4D-CT in parathyroid imaging, can provide information on the anatomy as well as the function of pathologic tissues. Both modalities provide excellent assessment of the extent of disease, local invasion and distant metastases. Drawbacks include cost and availability, and these should be weighed against benefits in the context of the management of thyroid and parathyroid disease.

  4. Modulation of experimental renal dysfunction of hereditary fructose intolerance by circulating parathyroid hormone.

    PubMed

    Morris, R C; McSherry, E; Sebastian, A

    1971-01-01

    In a woman with hereditary fructose intolerance and intact parathyroid function, the experimental administration of fructose at different dosage schedules invariably induced the dose-dependent, complex dysfunction of the proximal renal tubule now recognized as characteristic. But in a woman with hereditary fructose intolerance and hypoparathyroidism given similar amounts of fructose, the experimental dysfunction was strikingly attenuated or nondemonstrable unless or until fructose and parathyroid hormone were administered in sustained combination. Thereupon, a renal dysfunction of characteristic type and severity occurred invariably and almost immediately. Thus, the concentration of circulating parathyroid hormone can modulate the functional expression of the experimental renal disorder. This effect of parathyroid hormone, which appears to involve more than simple physiologic summation, may have important clinical implications.

  5. Parathyroid adenoma arising within the sternocleidomastoid muscle: a rare complication of autotransplantation.

    PubMed

    Touska, Philip; Srikanthan, Ahgi; Amarasinghe, Kavita; Jawad, Susan

    2016-07-20

    A 19-year-old patient presented with slowly enlarging, painless, left-sided cervical mass. She had a background of multiple endocrine neoplasia 2B and had undergone a total thyroidectomy for medullary thyroid carcinoma during childhood. A cervical recurrence was therefore suspected. Ultrasonographic and MRI examination revealed a well-defined lesion within the left sternocleidomastoid muscle. Further evaluation with sestamibi and single-photon emission CT revealed elevated tracer uptake within the lesion. Cytological analysis, following ultrasound-guided sampling, revealed absent staining for calcitonin and blood samples confirmed a normal serum calcitonin level; however, the serum parathyroid hormone level was elevated. Overall, summative findings were consistent with a diagnosis of a parathyroid adenoma arising within the left sternocleidomastoid muscle. Given that this is not a location for a physiological parathyroid tissue, the adenoma might have arisen within the autotransplanted parathyroid tissue, injected into the muscular sheath during thyroidectomy. The clinical, radiological and pathological features are considered in this article.

  6. Indocyanine green-enhanced fluorescence for assessing parathyroid perfusion during thyroidectomy

    PubMed Central

    Liu, Xiaoli; Wu, Chewei; Anuwong, Angkoon; Kim, Hoon Yub; Liu, Renbin; Randolph, Gregory W.; Inversini, Davide; Boni, Luigi; Rausei, Stefano; Frattini, Francesco; Dionigi, Gianlorenzo

    2016-01-01

    Identification of the parathyroid glands during thyroid surgery may prevent their inadvertent surgical removal and thus provide a better postoperative quality of life. Nevertheless, the most common “technique” for intraoperative evaluation of perfusion of parathyroid gland tissues during thyroid surgery is visual inspection of the physical condition of tissues, e.g., their color and bleeding edges. Another technique is measurement of intact parathyroid hormone. Recently, indocyanine green-enhanced fluorescence has been used in various surgical techniques, particularly laparoscopic surgery, to improve visualization and to provide detailed anatomical information. Fluorescent optical guidance helps surgeons to avoid inadvertent tissue injury while enhancing procedural efficiency. This technique has potential use for evaluating perfusion of the parathyroid gland in real-time intraoperative angiography. PMID:27867866

  7. Non-functional parathyroid carcinoma: a case report and review of the literature

    PubMed Central

    Wang, Liang; Han, Dali; Chen, Wanjun; Zhang, Shuguang; Wang, Zhiqi; Li, Ke; Gao, Yongsheng; Zou, Shujuan; Yang, Aiju

    2015-01-01

    Non-functional parathyroid carcinoma is an exceedingly rare disease with 31 reported cases since 1909. Because of the scarce number of cases of non-functional parathyroid carcinoma, there are no evidence-based recommendations for its optimal treatment. Surgery, including en bloc resection of the carcinoma, ipsilateral thyroid lobe and isthmus together with a neck dissection only in case of lymph node involvement, is the main treatment for non-functioning parathyroid carcinoma. The patient usually has a poorer prognosis because of detection at advanced stages, the relative ineffectiveness of adjuvant treatment modalities and the lack of adequate parameters for clinical follow-up. In this report, we present a case of non-functional parathyroid carcinoma at our institution, and we review the previous literature to discuss the latest advances in the diagnosis and treatment of this rare disease. PMID:26408508

  8. RNA immunoprecipitation for determining RNA-protein associations in vivo.

    PubMed

    Gilbert, Chris; Svejstrup, Jesper Q

    2006-08-01

    Similar to chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP) can be used to detect the association of individual proteins with specific nucleic acid regions, in this case on RNA. Live cells are treated with formaldehyde to generate protein-RNA cross-links between molecules that are in close proximity in vivo. RNA sequences that cross-link with a given protein are isolated by immunoprecipitation of the protein, and reversal of the formaldehyde cross-linking permits recovery and quantitative analysis of the immunoprecipitated RNA by reverse transcription PCR. The basics of RIP are very similar to those of ChIP, but with some important caveats. This unit describes the RIP procedure for Saccharomyces cerevisiae. Although the corresponding steps for metazoan cells have not yet been worked out, it is likely that the yeast procedure can easily be adapted for use in other organisms.

  9. A prospective cohort study of novel functional types of parathyroid glands in thyroidectomy

    PubMed Central

    Cui, Qiuxia; Li, Zhihua; Kong, Deguang; Wang, Kun; Wu, Gaosong

    2016-01-01

    Abstract The best method of preventing hypoparathyroidism after thyroidectomy is to keep parathyroid glands in situ. However, hypoparathyroidism still regularly occurs with the existing parathyroid classification system, and the incidence of permanent hypoparathyroidism has not been reduced. We created a novel system for classifying parathyroid glands that can guide parathyroid preservation in thyroidectomy. We prospectively observed parathyroid glands using the new system in 218 neck surgeries, compared with 132 under the traditional system from January 2014 to September 2015 at a single clinic center. Briefly, we classified parathyroid glands as follows: Type A, no dependency on the thyroid; B1, partial blood supply from the thyroid but retains adequate blood supply after removal of the thyroid; B2, partial blood supply from the thyroid and becomes devascularized after the removal of the thyroid; B3, blood supply mostly from the thyroid; and C, blood supply completely dependent on the thyroid. The classifications were used to decide between in situ preservation or auto-transplantation. The most common type of parathyroid gland was type B1 (53.77%), followed by type A (20.89%), which are the perfect categories for in situ preservation. Type B2 (17.52%) and type B3 (1.21%) have a chance to be kept in situ. For type C (6.61%), in situ preservation is impossible. When in-situ preservation is ruled out, parathyroid auto-transplantation is an alternative, with partial or total gland tissue, depending on the classification and the surgeon's discretion. Among the patients who were classified under the new system, 43.6% presented with transient hypoparathyroidism (symptoms lasting ≤6 months) after surgery, versus 42.4% in the old system, which was not a significant difference. However, permanent hypothyroidism (symptoms lasting >6 months) was not detected in the applied group, but in 3.0% of patients in the nonapplied group (P = 0.01). Our novel functional

  10. [Variations in the parathyroid glands. Number, situation and arterial vascularization. Anatomical study and surgical application].

    PubMed

    Delattre, J F; Flament, J B; Palot, J P; Pluot, M

    1982-11-01

    The authors have made a study of the variations in the parathyroid glands, basing their report on 100 block dissections of the neck injected with latex. The results allow a better understanding of certain types of parathyroid insufficiency following surgery to the thyroid gland. In almost half the cases the vascular arrangement was sufficient to explain how hypoparathyroidism might come about following surgery to the thyroid gland.

  11. Effects of maintenance lithium treatment on serum parathyroid hormone and calcium levels: a retrospective longitudinal naturalistic study

    PubMed Central

    Albert, Umberto; De Cori, David; Aguglia, Andrea; Barbaro, Francesca; Lanfranco, Fabio; Bogetto, Filippo; Maina, Giuseppe

    2015-01-01

    Objective The aim of this retrospective longitudinal naturalistic study was to evaluate the effects of maintenance lithium treatment on parathyroid hormone (PTH) and calcium levels. Methods A retrospective longitudinal naturalistic study design was used. Data were collected from the database of a tertiary psychiatric center covering the years 2010–2014. Included were bipolar patients who had never been exposed to lithium and had lithium started, and who had PTH, and total and ionized calcium levels available before and during lithium treatment. Paired t-tests were used to analyze changes in PTH and calcium levels. Linear regressions were performed, with mean lithium level and duration of lithium exposure as independent variables and change in PTH levels as dependent variable. Results A total 31 patients were included. The mean duration of lithium treatment was 18.6±11.4 months. PTH levels significantly increased during lithium treatment (+13.55±14.20 pg/mL); the rate of hyperparathyroidism was 12.9%. Neither total nor ionized calcium increased from baseline to follow-up; none of our patients developed hypercalcemia. Linear regressions analyses did not show an effect of duration of lithium exposure or mean lithium level on PTH levels. Conclusion Lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation, calcium and PTH should be added. PMID:26229473

  12. Effects of a 2X gravity environment on the ultrastructure of the gerbil parathyroid gland

    NASA Technical Reports Server (NTRS)

    Sannes, P. L.; Hayes, T. G.

    1975-01-01

    A number of studies concerning the effects of hypergravity on bone have shown increases in bone mass or bone dimensions. Correlative studies, which could provide clues to the mechanism for such a response, have been lacking. The purpose of the present study was to evaluate the ultrastructure of parathyroid glands of Mongolian gerbils exposed to a continuous 2 X gravity force for 60 d. It was found that the experimental animals had parathyroid glands which had a greater percentage of chief cells in the active stage of their secretory cycle when compared with control animals. This result was interpreted to indicate an increase in parathyroid gland secretory activity and, hence, an increase in parathyroid hormone release. It was suggested that increased parathyroid secretory activity was necessary to maintain serum calcium levels of hypergravity animals within normal limits. Cellular forms resembling water clear cells and highly compact, degenerating cells were described in experimental animals but not in controls. Areas suggestive of cellular dissolution and disorganization were also reported in experimental parathyroids.

  13. Preoperative parathyroid localization by superimposed iodine-131 toluidine blue and technetium-99m pertechnetate imaging

    SciTech Connect

    Zwas, S.T.; Czerniak, A.; Boruchowsky, S.; Avigad, I.; Wolfstein, I.

    1987-03-01

    A new parathyroid scintigraphic localization study by a dual radioisotope technique using radioiodinated toluidine blue (RTB) for the parathyroids and /sup 99m/Tc for thyroid imaging is presented. A simple RTB labeling procedure achieving 99% tagging of the /sup 131/I-TB was used. The RTB was found to be a highly specific parathyroid radiotracer, consequently enabling superimposition of the delineated thyroid gland over the RTB avid parathyroid foci without a need for subtraction of the thyroid or vascular background. Forty-six patients with primary hyperparathyroidism underwent scintigraphic study prior to cervical (41 patients) or mediastinal (5 patients) exploration and 67 pathological parathyroid glands (34 adenomas and 33 hyperplasias) were excised. On follow-up, serum calcium level returned to normal in all patients. Correlation of the scintigraphic results with the surgical findings disclosed a sensitivity of 93%, with a specificity of 80% and an overall accuracy of 87%. This new simplified and specific RTB scintigraphic method justifies its use as a routine procedure for preoperative parathyroid scintigraphic localization in primary hyperparathyroidism.

  14. The coexistence of primary hyperparathyroidism and thyroid nodules: should the preoperative work-up of the parathyroid and the thyroid diseases be specifically adjusted?

    PubMed Central

    SCERRINO, G.; ATTARD, M.; LO PICCOLO, C.; ATTARD, A.; MELFA, G.I.; RASPANTI, C.; ZARCONE, M.; BONVENTRE, S.; MAZZOLA, S.; GULOTTA, G.

    2016-01-01

    Introduction and objectives Primary hyperparathyroidism (PHPT) can be found in concomitance with thyroid disease (TD) in a high frequency of cases. In this context the diagnostic exams for localizing the enlarged parathyroid(s) gland(s) could be less reliable or non-conclusive. Moreover, the thyroid carcinoma seems to be more frequent compared to that isolated thyroid desease and, therefore, carefully investigated. The main goal of the present study is to evaluate which diagnostic tool (US, MIBI) is more reliable for localizing the site of the PTH hypersecretion and to confirm if it is always advantageous a combination of both exams. Besides, we evaluated the incidence of thyroid carcinoma in our series of patients. Patients and methods A review of available data of 73 patients who underwent total thyroidectomy + parathyroidectomy from 2003 and 2014 was performed. The preoperative workup included systematically US and MIBI whose results were considered true positive when at least the side (left/right) of the parathyroid affected were concordant with the surgical report, settled as the gold standard, according to the Cox non-nested model. The connection between the diagnostic results of US versus MIBI was calculated with the Cohen K index for evaluating their overlap. The average of the thyroid carcinoma were also calculated. Results The difference between respectively US versus surgical report (p value=0.73) and MIBI versus surgical report (p value=0.81) were not significant. The low Cohen K index showed that both US and MIBI are complementary. In 23 patients (32,9%) a thyroid carcinoma was found. Conclusions The association of MIBI and neck US is mandatory in the first evaluation of patients undergoing thyroidectomy and parathyroid excision simultaneously. The high prevalence of thyroid carcinoma in this specific context suggests a more aggressive diagnostic and surgical behaviour. PMID:27734796

  15. Application of carbon nanoparticles in lymph node dissection and parathyroid protection during thyroid cancer surgeries: a systematic review and meta-analysis

    PubMed Central

    Wang, Lun; Yang, Dong; Lv, Jun-Yuan; Yu, Dan; Xin, Shi-Jie

    2017-01-01

    Purpose To investigate whether carbon nanoparticles (CNs) are helpful in identifying lymph nodes and metastatic lymph nodes and in parathyroid protection during thyroid cancer surgery. Methods English and Chinese literature in PubMed, Cochrane Database of Systematic Reviews, EMBASE, ClinicalTrials.gov, China Biology Medicine Database, China National Knowledge Infrastructure, China Master’s and Doctoral Theses Full-Text Database, Wanfang database, and Cqvip database were searched (till March 22, 2016). Randomized controlled trials (RCTs) that compared the use of CNs with a blank control in patients undergoing thyroid cancer surgery were included. Quality assessment and data extraction were performed, and a meta-analysis was conducted using RevMan 5.1 software. The primary outcomes were the number of retrieved central lymph nodes and metastatic lymph nodes, and the rate of accidental parathyroid removal. Results We obtained 149 relevant studies, and only 47 RCTs with 4,605 patients (CN group: n=2,197; blank control group: n=2,408) met the inclusion criteria. Compared with the control group, the CN group was associated with more retrieved lymph nodes/patient (weighted mean difference [WMD]: 3.39, 95% confidence interval [CI]: 2.73–4.05), more retrieved metastatic lymph nodes (WMD: 0.98, 95% CI: 0.61–1.35), lower rate of accidental parathyroid removal, and lower rates of hypoparathyroidism and hypocalcemia. However, the total metastatic rate of the retrieved lymph nodes did not differ between the groups (odds ratio: 1.13, 95% CI: 0.87–1.47, P=0.35). Conclusion CNs can improve the extent of neck dissection and protect the parathyroid glands during thyroid cancer surgery. And the number of identified metastatic lymph nodes can be simultaneously increased. PMID:28280359

  16. Multiple endocrine neoplasia type 1 with anterior mediastinal parathyroid adenoma: successful localization using Tc-99m sestamibi SPECT/CT

    PubMed Central

    Park, Hye Lim; Kim, Sung Hoon; Lee, Sohee

    2016-01-01

    The most common manifestation of multiple endocrine neoplasia type 1 (MEN1) is hyperparathyroidism. Treatment of hyperparathyroidism in MEN patients is surgical removal of the parathyroid glands, however ectopic parathyroid gland is challenging for treatment. A 51-year-old female, the eldest of 3 MEN1 sisters, had hyperparathyroidism with ectopic parathyroid adenoma in the mediastinal para-aortic region, which was detected by technetium-99m (Tc-99m) sestamibi scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT). She underwent total parathyroidectomy with video-assisted thoracoscopic surgery on an anterior mediastinal mass. Anterior mediastinal parathyroid adenoma in MEN1 patients is rare. Precise localization of an ectopic parathyroid gland with Tc-99m sestamibi SPECT/CT can lead to successful treatment of hyperparathyroidism. This is the first reported case in the literature of mediastinal parathyroid adenoma in MEN1 patient visualized by Tc-99m sestamibi SPECT/CT. PMID:27904855

  17. Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma

    PubMed Central

    NAGAMINE, KYOSUKE; KITAMURA, TETSUYA; YANAGAWA-MATSUDA, AYA; OHIRO, YOICHI; TEI, KANCHU; HIDA, KYOKO; HIGASHINO, FUMIHIRO; TOTSUKA, YASUNORI; SHINDOH, MASANOBU

    2013-01-01

    Parathyroid hormone-related protein (PTHrP) is known to induce bone resorption by activating RANKL as well as PTH. PTHrP plays a central role in humoral hypercalcemia, and its expression has been reported to be closely associated with bone metastasis of breast carcinoma. PTHrP expression in oral squamous carcinoma cell lines was investigated, and PTHrP was expressed in oral squamous cell carcinoma cell lines similar to that in a prostate carcinoma cell line. Mucoepidermoid carcinoma is the most common malignant salivary gland tumor composed of different types of cells including a squamous component. Its clinical behavior is highly variable and ranges from slow-growing and indolent to locally aggressive and highly metastatic. We examined the PTHrP expression in mucoepidermoid carcinoma and assessed the significance of its correlation with clinicopathological features. Immunohistochemical detection of PTHrP was carried out in 21 cases of mucoepidermoid carcinoma in the head and neck region. PTHrP was highly detectable in intermediate and epidermoid cells, and abundant expression of PTHrP in intermediate cells had a significant association with cancer malignancy, including lymph node metastasis and/or tumor recurrence. These results suggest that PTHrP expression can be used as a prognostic factor for mucoepidermoid carcinoma. PMID:23588777

  18. BMI but Not Race Contributes to Vitamin D–Parathyroid Hormone Axis in Peripubertal Girls

    PubMed Central

    Hanks, Lynae J.; Ashraf, Ambika; Alvarez, Jessica A.; Beasley, T. Mark; Fernandez, Jose R.; Casazza, Krista

    2015-01-01

    Currently, there is widespread interest in establishing 25-hydroxy vitamin D (25OHD) level preventing a secondary elevation in parathyroid hormone (PTH). The aim of this study was to identify the 25OHD nadir resulting in a rise of PTH and to determine if this inflection point is weight- or race-specific during growth and development in peripubertal girls. A total of 104 normal (n = 61) and overweight (n = 43) African American (AA) and European American (EA) girls, 5 to 14 years of age, were included. Though AAs had lower 25OHD levels, there was no difference in PTH compared with EAs. A 25OHD concentration of 27.2 ng/mL (P < .01) was indicated to increase PTH in normal-weight girls, although a statistically significant level was not established in overweight girls. No race difference in inflection point was observed. These data suggest a potential influence of weight status on the 25OHD-PTH inflection point in peripubertal girls. Accordingly, on determination of 25OHD level reflecting optimal health, consideration of weight status appears to be important during this critical period of growth and development. PMID:26236422

  19. Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Nashimoto, Mitsue; Yamamoto, Masaharu

    Serum 25-hydroxyvitamin D3 [25(OH)D3] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D3 and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45-81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D3 and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D3 [Δ25(OH)D3] and intact PTH concentrations were -18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D3 levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D3 values having greater reductions in winter 25(OH)D3 concentrations. There were inter-individual differences in Δ25(OH)D3, although the summer and winter 25(OH)D3 concentrations were well-correlated. Since Δ25(OH)D3 was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D3 concentrations of an individual appeared to reflect her ability to produce 25(OH)D3 photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D3, i.e., one with a low 25(OH)D3 level.

  20. 77 FR 14043 - Certain Mobile Devices, Associated Software, and Components Thereof; Determination To Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ... COMMISSION Certain Mobile Devices, Associated Software, and Components Thereof; Determination To Review Final... certain mobile devices, associated software, and components thereof by reason of infringement of U.S... mobile devices, associated software, and components thereof containing same by reason of infringement...

  1. Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis

    PubMed Central

    1986-01-01

    Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease. PMID:3528379

  2. Parathyroid hormone-related protein in lower vertebrates.

    PubMed

    Ingleton, P M

    2002-05-01

    The genes for parathyroid hormone-related protein (PTHrP) have been cloned in two teleost fishes, cDNA of sea bream (Sparus aurata) and genomic DNA of puffer fish (Fugu rubripes). The gene sequences show that there is significant conservation of amino acid identity, with specific domains most highly conserved. The N-terminus, responsible for bone matrix lysis in mammals and chickens, is present in the fish genes with 52% sequence identity to higher vertebrate PTHrP peptides; the nuclear transporter region shares 73% identity, and the RNA-binding sequence is 65% identical. However, the peptides are shorter then mammalian PTHrP, lacking the C-terminus responsible for inhibition of osteoclast lytic activity, but they have an additional inserted sequence between amino acids 38 and 54 that is not present in higher vertebrate PTHrPs. The N-terminus 1-38 Fugu PTHrP proved to be hypercalcaemic in larval Sparus, suggesting that it may be a physiological regulator of calcium homeostasis in fish. Using homologous nucleotide probes for in situ hybridisation and reverse-transcription polymerase chain reaction (RT-PCR) of extracted RNA, PTHrP gene expression has been widely found in both developing and adult fish. Antiserum to the fish insert sequence demonstrated transcription of PTHrP in all stages of Sparus development, and also detected the same epitope in tissues of developing frog (Rana temporaria), indicating that this has been retained during evolution of the amphibia.

  3. Genomic profiling reveals mutational landscape in parathyroid carcinomas

    PubMed Central

    Bellizzi, Justin; Lau, Chun Yee; Moe, Aye S.; Strahl, Maya; Newman, Leah C.; Fink, Marc Y.; Antipin, Yevgeniy; Yu, Willie; Stevenson, Mark; Cavaco, Branca M.; Thakker, Rajesh V.; Morreau, Hans; Schadt, Eric E.; Sebra, Robert; Li, Shuyu D.

    2017-01-01

    Parathyroid carcinoma (PC) is an extremely rare malignancy lacking effective therapeutic intervention. We generated and analyzed whole-exome sequencing data from 17 patients to identify somatic and germline genetic alterations. A panel of selected genes was sequenced in a 7-tumor expansion cohort. We show that 47% (8 of 17) of the tumors harbor somatic mutations in the CDC73 tumor suppressor, with germline inactivating variants in 4 of the 8 patients. The PI3K/AKT/mTOR pathway was altered in 21% of the 24 cases, revealing a major oncogenic pathway in PC. We observed CCND1 amplification in 29% of the 17 patients, and a previously unreported recurrent mutation in putative kinase ADCK1. We identified the first sporadic PCs with somatic mutations in the Wnt canonical pathway, complementing previously described epigenetic mechanisms mediating Wnt activation. This is the largest genomic sequencing study of PC, and represents major progress toward a full molecular characterization of this rare malignancy to inform improved and individualized treatments. PMID:28352668

  4. Pulsatile Release of Parathyroid Hormone from an Implantable Delivery System

    PubMed Central

    Liu, Xiaohua; Pettway, Glenda J.; McCauley, Laurie K.; Ma, Peter X.

    2007-01-01

    Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(lactic acid) (PLLA), using a reverse solid free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(p-carboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies. PMID:17576005

  5. Unusual ¹⁸F-FDG PET/CT finding of an oxyphil parathyroid adenoma in a patient with Hodgkin's Lymphoma.

    PubMed

    Niccoli-Asabella, Artor; Ferrari, Cristina; Antonica, Filippo; Scardapane, Arnaldo; Rubini, Domenico; Rubini, Giuseppe

    2014-01-01

    Malignancy-associated hypercalcemia is a complication of advanced tumours that is associated to a poor prognosis. Thorough evaluation to establish its cause is essential because some patients may actually have undiagnosed primary hyperparathyroidism. We report a case of a patient affected by Hodgkin's Lymphoma and persistent hypercalcemia with an incidental (18)F-FDG PET/CT finding in the anterior neck region, not ascribable to malignancy, confirmed with (99m)Tc-sestamibi scintigraphy. It was removed by minimally invasive surgery. It was shown to be an oxyphil parathyroid adenoma localized in an unusual site.

  6. Regulation of Articular Chondrocyte Proliferation and Differentiation by Indian Hedgehog and Parathyroid Hormone-related Protein

    PubMed Central

    Chen, Xuesong; Macica, Carolyn; Nasiri, Ali; Broadus, Arthur E.

    2008-01-01

    Objective The chondrocytes of the epiphyseal growth zone are regulated by the Indian hedgehog (Ihh)-parathyroid hormone-related protein (PTHrP) axis. In weight-bearing joints, this growth zone comes to be subdivided by the secondary ossification center into distinct articular and growth cartilage structures. Here, we explored the cells of origin, localization, regulation of expression, and putative functions of Ihh and PTHrP in articular cartilage in the mouse. Methods We assessed Ihh and PTHrP expression in an allelic PTHrP-lacZ knockin mouse and several versions of PTHrP-null mice. Selected joints were unloaded surgically to examine load-induction of PTHrP and Ihh. Results The embryonic growth zone appears to serve as the source of PTHrP-expressing proliferative chondrocytes that populate both the forming articular cartilage and growth plate structures. In articular cartilage, these cells take the form of articular chondrocytes in the mid-zone. In PTHrP-knockout mice, mineralizing chondrocytes encroach upon developing articular cartilage but appear to be prevented from mineralizing the joint space by Ihh-driven surface chondrocyte proliferation. In growing and adult mice, PTHrP expression in articular chondrocytes is load-induced, and unloading is associated with rapid changes in PTHrP expression and articular chondrocyte differentiation. Conclusion We conclude that the PTHrP-Ihh axis participates in the maintenance of articular cartilage. Dysregulation of this system might contribute to the pathogenesis of arthritis. PMID:19035497

  7. Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Ryder, K. D.; Duncan, R. L.

    2000-01-01

    Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

  8. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    PubMed Central

    Falzon, Miriam; Bhatia, Vandanajay

    2015-01-01

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation. PMID:26095761

  9. Effect of parathyroid hormone on transport by toad and turtle bladder

    SciTech Connect

    Sabatini, S.; Kurtzman, N.A.

    1987-01-01

    The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H/sub 2/O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H/sub 2/O and Na transport and H..mu.. secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H/sub 2/O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P < 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H/sup +/ secretion in turtle bladders. Both PTH and A23187 increased /sup 45/Ca uptake in toad bladder epithelial cells; only A23187 increased /sup 45/Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different.

  10. Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

    PubMed

    Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi

    2015-03-01

    Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL.

  11. Molecular recognition of parathyroid hormone by its G protein-coupled receptor

    SciTech Connect

    Pioszak, Augen A.; Xu, H. Eric

    2008-08-07

    Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineered as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-{angstrom} structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer {alpha}-{beta}-{beta}{alpha} fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway.

  12. Reduction of Parathyroid Hormone with Vitamin D Supplementation in Blacks: A Randomized Controlled Trial

    PubMed Central

    Chandler, Paulette D.; Agboola, Foluso; Ng, Kimmie; Scott, Jamil B.; Drake, Bettina F.; Bennett, Gary G.; Chan, Andrew T.; Hollis, Bruce W.; Emmons, Karen M.; Fuchs, Charles S.; Giovannucci, Edward L.

    2015-01-01

    Background Response of parathyroid hormone (PTH) to vitamin D supplementation is determined by the baseline PTH level and change in vitamin D status. Conflicting reports in Blacks exist on the PTH response to vitamin D to supplementation. Methods During 3 winters from 2007-2010, 328 healthy Blacks (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. PTH was measured in 254 participants at baseline and at the end of vitamin D supplementation period. Results The differences in PTH between baseline and 3 months were 3.93 pg/mL for those receiving placebo, -3.37 pg/mL for those receiving 1000 IU/d, -6.76 pg/mL for those receiving 2000 IU/d, and -8.99 pg/mL for those receiving 4000 IU/d ( -2.98 pg/mL for each additional 1000 IU/d of vitamin D3; p<0.001). Conclusion We found a significant decrease in PTH with increasing doses of vitamin D supplementation up to intakes of 4000 IU/d in Blacks. Clinical Trials.gov: NCT00585637 PMID:26858840

  13. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  14. Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.

    1997-01-01

    To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

  15. Detection of parathyroid hormone using an electrochemical impedance biosensor based on PAMAM dendrimers.

    PubMed

    Özcan, Hakkı Mevlüt; Sezgintürk, Mustafa Kemal

    2015-01-01

    This paper presents a novel hormone-based impedimetric biosensor to determine parathyroid hormone (PTH) level in serum for diagnosis and monitoring treatment of hyperparathyroidism, hypoparathyroidism and thyroid cancer. The interaction between PTH and the biosensor was investigated by an electrochemical method. The biosensor was based on the gold electrode modified by 12-mercapto dodecanoic (12MDDA). Antiparathyroid hormone (anti-PTH) was covalently immobilized on to poly amidoamine dendrimer (PAMAM) which was bound to a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) couple, self-assembled monolayer structure from one of the other NH2 sites. The immobilization of anti-PTH was monitored by electrochemical impedance spectroscopy, cyclic voltammetry and scanning electron microscope techniques. After the optimization studies of immobilization materials such as 12MDDA, EDC-NHS, PAMAM, and glutaraldehyde, the performance of the biosensor was investigated in terms of linearity, sensitivity, repeatability, and reproducibility. PTH was detected within a linear range of 10-60 fg/mL. Finally the described biosensor was used to monitor PTH levels in artificial serum samples.

  16. Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy

    PubMed Central

    Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

    2014-01-01

    Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

  17. Preoperative localization of hyperfunctioning parathyroid glands with 4D-CT.

    PubMed

    Lundstroem, Anke Katrin; Trolle, Waldemar; Soerensen, Christian Hjort; Myschetzky, Peter Sand

    2016-05-01

    Primary hyperparathyroidism (pHPT) is almost exclusively the result of a solitary parathyroid adenoma. In most cases, the affected gland can be surgically removed, but precise preoperative imaging is essential for adenoma localization prior to surgical intervention. In this study, we evaluated the diagnostic value of four-dimensional computed tomography (4D-CT) as a preoperative imaging tool in relation to the localization of pathologic parathyroid glands in patients with pHPT and negative sestamibi scans. This study included 43 consecutive patients with pHPT referred for parathyroidectomy at the Department of Head and Neck Surgery of Copenhagen University Hospital Rigshospitalet in 2011 and 2012. All patients had a 4D-CT performed prior to parathyroidectomy. CT localization of the suspected adenoma was correlated to the actual surgical findings and subsequent histological diagnosis was also available as references for the accuracy of this imaging tool. Hyperfunctioning parathyroid glands were found in 40 patients. 4D-CT identified 32 solitary hyperfunctioning parathyroid glands located on the correct side of the neck (PPV 76 %) and 21 located within the correct quadrant (PPV 49 %). Unilateral resection was performed in 72 % of patients due to the localization findings of preoperative imaging. 4D-CT can, therefore, be considered an effective method for the preoperative localization of parathyroid adenomas and is an important tool in surgical intervention for patients referred to parathyroidectomy.

  18. Ultrastructural evaluation of parathyroid glands and thyroid C cells of cattle fed Solanum malacoxylon.

    PubMed Central

    Collins, W. T.; Capen, C. C.; Döbereiner, J.; Tokarnia, C. H.

    1977-01-01

    Fine structural alterations of thyroid C cells and parathyroid chief cells were evaluated after feeding dried leaves of the calcinogenic plant, Solanum malacoxylon, to cattle for 1, 6 and 32 days. Thyroid C cells initially were degranulated in response to the hypercalcemia, and parathyroid chief cells accumulated secretory granules. There was hypertrophy of thyroid C cells with well-developed secretory organelles but few secretory granules in the cytoplasm after 6 days of feeding S. malacoxylon. Inactive chief cells with dispersed profiles of endoplasmic reticulum and increased lysosomal bodies predominated in the parathyroid glands. Multiple foci of soft tissue mineralization were present in the heart, lung, and kidney. Thyroid C cells underwent hypertrophy and hyperplasia after 32 days of S. malacoxylon, and parathyroid chief cells were inactive or atrophic in response to the long-term hypercalcemia. Severe soft tissue mineralization was present throughout the cardiovascular system, lung, kidney, and spleen. These ultrastructural changes in thyroid C cells and parathyroid chief cells plus the widespread soft tissue mineralization observed after feeding cattle small amounts of S. malacoxylon are consistent with the recent evidence that leaves of this plant are a potent source of the active metabolite, 1,25-dihydroxycholecalciferol, of vitamin D. Images Figure 7 Figure 8 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:869016

  19. Etiology of hyperparathyroidism and bone disease during chronic hemodialysis. 3. Evaluation of parathyroid suppressibility.

    PubMed

    Goldsmith, R S; Furszyfer, J; Johnson, W J; Fournier, A E; Sizemore, G W; Arnaud, C D

    1973-01-01

    Parathyroid function was assessed by calcium infusions (4-8 h) in 16 patients with chronic renal insufficiency being treated by long-term hemodialysis. The concentrations of two immunoreactive species of parathyroid hormone in plasma (iPTH-9, mol wt 9500; iPTH-7, mol wt 7000) were estimated by radioimmunoassays utilizing two relatively specific antisera. Control values of the smaller species, iPTH-7, were uniformly high, whereas values of iPTH-9 were normal in 12 of 19 studies. Response of iPTH-7 to calcium infusions was variable, with significant decreases occurring only five times in 27 infusions. Concentrations of iPTH-9, however, decreased during every calcium infusion. In contrast to these acute responses, five of six patients studied during periods of dialysis against both low (< 6 mg/100 ml) and high (7-8 mg/100 ml) calcium concentrations in the dialyzate showed a decrease in values of iPTH-7 during the period of dialysis against the higher calcium concentration. It is concluded that plasma concentrations of iPTH-9 reflect primarily the moment-to-moment secretory status of the parathyroid glands, while concentrations of iPTH-7 reflect more closely chronic parathyroid functional status. It is further concluded that the failure of iPTH-7 to decrease during induced hypercalcemia should not be equated with autonomy of parathyroid gland function.

  20. Desensitization of parathyroid hormone receptors on cultured bone cells

    SciTech Connect

    Pun, K.K.; Ho, P.W.; Nissenson, R.A.; Arnaud, C.D. )

    1990-12-01

    Administration of excessive amounts of parathyroid hormone (PTH) in the treatment of osteoporosis can reverse the beneficial effects of a low-dose, intermittent regime. To investigate the direct actions and the possible cellular mechanisms of PTH in inducing desensitization of PTH receptors, we studied the effects of desensitization on rat osteoblastic UMR-106 cells. When the osteoblasts were preincubated with bPTH-(1-34), complete refractoriness to a subsequent challenge with the hormone developed within 1 h and at hormone concentrations as low as 5 nM. When osteoblasts thus desensitized were incubated in hormone-free medium, recovery of the cAMP responses began within 2 h and reached maximum after 16 h. Cycloheximide did not affect the process of desensitization. (Nle8,Nle18,Tyr34)bPTH-(3-34)amide significantly impaired the desensitization process by PTH-(1-34) but did not have stimulatory effect on cAMP responses. No significant heterologous desensitization was obvious after preincubation with isoprenaline (50 microM), prostaglandin E1 (50 microM), or prostaglandin E2 (50 microM) for 2 h. Binding experiments with (125I)PLP-(1-36)amide after desensitization revealed that there was an approximate twofold decrease in receptor affinities as analyzed by Scatchard analysis, showing that the decrease in affinity was prominent in the process of desensitization. When the cells were treated with monensin during desensitization, PTH challenge after desensitization produced significantly lower cyclic AMP responses. Recovery after desensitization occurred over a period of 16 h. Inclusion of monensin, but not cycloheximide, impaired the recovery. The results show that homologous desensitization of rat osteoblasts to PTH is brought about by the occupancy of receptors by PTH-(1-34) but not by cAMP generation itself.

  1. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

    PubMed Central

    Dobolyi, Arpád; Dimitrov, Eugene; Palkovits, Miklós; Usdin, Ted B.

    2012-01-01

    The G-protein coupled parathyroid hormone 2 receptor (PTH2R) is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand, tuberoinfundibular peptide of 39 residues (TIP39), is synthesized in only two brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine-vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control neuroendocrine disorders

  2. Influence of prolactin administration on the ultimobranchial body and parathyroid glands of the freshwater snake, Natrix piscator.

    PubMed

    Srivastav, A K; Rani, L; Sasayama, Y

    1994-05-01

    The effects of ovine prolactin (10 I.U./100 g body wt) on the ultimobranchial body and parathyroid glands were investigated in Natrix piscator for 15 days. The ultimobranchial body of the prolactin treated specimens depicts signs of increased activity whereas the parathyroid glands exhibit reduced activity.

  3. Calcium-sensing receptor activation in chronic kidney disease: effects beyond parathyroid hormone control.

    PubMed

    Massy, Ziad A; Hénaut, Lucie; Larsson, Tobias E; Vervloet, Marc G

    2014-11-01

    Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD). Cinacalcet, an allosteric modulator of the calcium-sensing receptor (CaSR) expressed in parathyroid glands, is the only calcimimetic approved to treat SHPT in patients on dialysis. By enhancing CaSR sensitivity for plasma extracellular calcium (Ca(2+)0), cinacalcet reduces serum parathyroid hormone, Ca(2+)0, and serum inorganic phosphorous concentrations, allowing better control of SHPT and CKD-mineral and bone disorders. Of interest, the CaSR also is expressed in a variety of tissues where its activation regulates diverse cellular processes, including secretion, apoptosis, and proliferation. Thus, the existence of potential off-target effects of cinacalcet cannot be neglected. This review summarizes our current knowledge concerning the potential role(s) of the CaSR expressed in various tissues in CKD-related disorders, independently of parathyroid hormone control.

  4. The Calcium-Sensing Receptor and the Parathyroid: Past, Present, Future

    PubMed Central

    Conigrave, Arthur D.

    2016-01-01

    Parathyroid hormone (PTH) defends the extracellular fluid from hypocalcemia and has powerful and well-documented actions on the skeleton and renal tubular system. To achieve a satisfactory stable plasma calcium level, the secretion of PTH, and the resulting serum PTH level, is titrated carefully to the prevailing plasma ionized Ca2+ concentration via a Ca2+ sensing mechanism that mediates feedback inhibition of PTH secretion. Herein, I consider the properties of the parathyroid Ca2+ sensing mechanism, the identity of the Ca2+ sensor, the intracellular biochemical mechanisms that it controls, the manner of its integration with other components of the PTH secretion control mechanism, and its modulation by other nutrients. Together the well-established, recently elucidated, and yet-to-be discovered elements of the story constitute the past, present, and future of the parathyroid and its calcium-sensing receptor (CaSR). PMID:28018229

  5. 77 FR 35427 - Certain Mobile Devices, Associated Software, and Components Thereof Final Determination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... COMMISSION Certain Mobile Devices, Associated Software, and Components Thereof Final Determination of... software, and components thereof by reason of infringement of U.S. Patent Nos. 5,579,517 (``the `517 patent... the United States after importation of certain mobile devices, associated software, and...

  6. 77 FR 43155 - Guidance on Due Diligence Requirements for Savings Associations in Determining Whether a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ... Whether a Corporate Debt Security Is Eligible for Investment AGENCY: Federal Deposit Insurance Corporation... associations in conducting due diligence to determine whether a corporate debt security is eligible for...'') to prohibit a savings association from acquiring or retaining a corporate debt security that does...

  7. Recurrent hyperparathyroidism due to proliferation of autotransplanted parathyroid tissue in a multiple endocrine neoplasia type 2A patient

    PubMed Central

    Kim, Bong Kyun; Lee, Jina

    2016-01-01

    About 20%–30% of all cases of multiple endocrine neoplasia type 2A (MEN 2A) is accompanied by primary hyperparathyroidism. These patients undergo parathyroidectomy and, if needed, autotransplantation. In rare cases, autotransplanted parathyroid tissues can cause hypoparathyroidism due to failure of transplantation or hyperparathyroidism due to proliferation of the transplanted tissue. A 68-year-old female with MEN 2A underwent left adrenalectomy for pheochromocytoma 15 years prior to presentation and total thyroidectomy, central and right lateral neck lymph node dissection, and subtotal parathyroidectomy with autotransplantation for medullary thyroid cancer and primary hyperparathyroidism 6 years previous. Recently, a doubtful parathyroid adenoma was detected in the left sternocleidomastoid muscle on ultrasonography and on an additional sestamibi scan. The mass was excised and histologically confirmed as parathyroid adenoma. This is a very rare case, and it suggests that long-term regular monitoring of serum calcium and intact parathyroid hormone levels is necessary after parathyroid autotransplantation. PMID:27617256

  8. [Prognostication of acute-pancreatitis-associated pulmonary injury based on determination of cytokines levels].

    PubMed

    Fedorkiv, M B; Hudz, I M; Shevchuk, I M

    2013-07-01

    The results of examination of 68 patients, admitted to hospital for an acute pancreatitis during 48 h from its occurrence, were analyzed. In all the patients the cytokines (IL-8, IL-10, TNF-alpha) content was determined in the blood, using immunoenzymal analysis. Algorithm of prognostication of an acute pancreatitis-associated pulmonary injury, basing on determination of the cytokines contents, was elaborated.

  9. [Thymic ectopia and parathyroid tissue in the pangolin (Manis tricuspis Rafinesque)].

    PubMed

    Bureau, J P; Senelar, R; Serrou, B; Kreher, P

    1975-09-01

    Thymic ectopies are under study in 45 Pangolin's thyroids (Manis tricuspis Rafinesque). Their frequency seems to be independent of the sex of the animal but this frequency also appears to be in relation to the age of the animal. The topographic and morphological studies suggest a close relationship between these inclusions made out of thymic tissue and the presence of parathyroid islets included into the thyroid capsule. Some pictures, showing a connection between parathyroid cells and thymis parenchym elements, plead in favour of a functional interelation between these different structures as the Mc Manus experiments suggest it.

  10. Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility.

    PubMed

    Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A

    2016-06-01

    Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility.

  11. Relationship of Vitamin D and Parathyroid Hormone to Obesity and Body Composition in African Americans

    PubMed Central

    Valiña-Tóth, Anna Liza B.; Lai, Zongshan; Yoo, Wonsuk; Abou-Samra, Abdul; Gadegbeku, Crystal A.; Flack, John M.

    2009-01-01

    Background Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25-hydroxyvitamin D (25-OH D) and elevated parathyroid hormone (PTH). The relationship of 25-OH D and PTH to body composition and size in AA is not well known. Objective To determine the relationship of 25-OH D and PTH levels with body composition and anthropometric measures. Design A cross-sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS-sponsored weight loss/salt sensitivity. Measurements Multivariable linear regression analyses were used to explore the relationship of 25-OH D and PTH with body composition, determined by dual-energy X-ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: 1) normal (25-OH D > 50 nmol/l, PTH ≤ 65 pg/ml), 2) low 25-OH D and normal PTH, and 3) low 25-OH D and high PTH. Results Age, sex and season-adjusted regression analyses showed that PTH was directly correlated with total (p=0.02), truncal (p=0.03) and extremity (p=0.03) fat mass while 25-OH D was related inversely to truncal fat mass (p=0.02). Total fat mass in groups 1–3, respectively, was 30.0, 34.0, to 37.4 kg (p=0.008); truncal fat mass was 13.4, 15.9 and 17.6 kg (p=0.006) and extremity fat mass was 15.8, 16.9 and 19.7 kg (p=0.02). Lean mass did not differ across the 3 groups. Conclusions Our findings show that lower 25-OH D and raised PTH are both correlated, though in opposite directions, with fat mass, fat distribution and anthropometric measures in adult AA. PMID:19656160

  12. Determining annual suspended sediment and sediment-associated trace element and nutrient fluxes

    USGS Publications Warehouse

    Horowitz, A.J.

    2008-01-01

    Suspended sediment is a major factor in the biological and geochemical cycling of trace elements and nutrients in aquatic systems. The design of effective studies involving the collection, processing, and subsequent chemical analysis of suspended sediment requires a clear understanding of the problems associated with using this sample medium. This review summarizes the current state of knowledge relative to the various issues/problems associated with the collection of representative suspended sediment samples in fluvial systems. It also addresses issues associated with accurately determining the concentrations and fluxes of sediment-associated trace elements and nutrients.

  13. Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.

    PubMed Central

    Shen, V; Dempster, D W; Birchman, R; Xu, R; Lindsay, R

    1993-01-01

    To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen (17 beta-estradiol, 30 micrograms/kg per d, s.c.) and parathyroid hormone (rPTH [1-34], 40 micrograms/kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning 1 wk post-Ovx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis. PMID:8514860

  14. MOLECULAR MODELS OF PARATHYROID METABOLISM BY CARBOXYLESTERASES: DIFFERENTIAL EFFECTS DUE TO STEREOCHEMISTRY.

    EPA Science Inventory

    PARATHYROIDS ARE A CHEMICAL CLASS OF WIDELY USED INSECTICIDES, & AT LEAST 16 CHEMICALS IN THIS CLASS ARE REGISTERED FOR USE IN THE US. IN ORDER TO EXTRAPOLATE THE KNOWLEDGE FROM RODENTS TO HUMANS, PHYSIOLOGICALLY-BASED PHARMACOKINETIC (pbpk) MODELS ARE CURRENTLY BEING DEVELOPED.

  15. The use of cinacalcet in pregnancy to treat a complex case of parathyroid carcinoma

    PubMed Central

    Bailey, M; Chahal, H; Raja, O; Bhat, R; Gayle, C; Grossman, A B; Druce, M R

    2014-01-01

    Summary We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG–PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia. Learning points Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity. PMID:25298882

  16. Tissue-specific roles for sonic hedgehog signaling in establishing thymus and parathyroid organ fate.

    PubMed

    Bain, Virginia E; Gordon, Julie; O'Neil, John D; Ramos, Isaias; Richie, Ellen R; Manley, Nancy R

    2016-11-01

    The thymus and parathyroids develop from third pharyngeal pouch (3rd pp) endoderm. Our previous studies show that Shh null mice have smaller, aparathyroid primordia in which thymus fate specification extends into the pharynx. SHH signaling is active in both dorsal pouch endoderm and neighboring neural crest (NC) mesenchyme. It is unclear which target tissue of SHH signaling is required for the patterning defects in Shh mutants. Here, we used a genetic approach to ectopically activate or delete the SHH signal transducer Smo in either pp endoderm or NC mesenchyme. Although no manipulation recapitulated the Shh null phenotype, manipulation of SHH signaling in either the endoderm or NC mesenchyme had direct and indirect effects on both cell types during fate specification and organogenesis. SHH pathway activation throughout pouch endoderm activated ectopic Tbx1 expression and partially suppressed the thymus-specific transcription factor Foxn1, identifying Tbx1 as a key target of SHH signaling in the 3rd pp. However, ectopic SHH signaling was insufficient to expand the GCM2-positive parathyroid domain, indicating that multiple inputs, some of which might be independent of SHH signaling, are required for parathyroid fate specification. These data support a model in which SHH signaling plays both positive and negative roles in patterning and organogenesis of the thymus and parathyroids.

  17. Parathyroid function in uremic children during periods of renal insufficiency, hemodialysis, and transplantation.

    PubMed

    Gruskin, A B; Root, A W; Duckett, G E; Baluarte, H J

    1976-11-01

    Function of the parathyroid gland was evaluated in children with renal insufficiency prior to and after imitation of hemodialysis, and again following renal transplantation. Serum levels of immunoreactive parathyroid hormone responded appropriately to increases or decreases of serum calcium concentrations in the three groups. Functional and histologic studies in the children with renal insufficiency demonstrated the cause of their elevated circulating levels of iPTH to be diffuse parathyroid hyperplasia. During hemodialysis, the serum concentration of calcium rose and that of iPTH decreased, when the calcium gradient between the dialysate and the blood favored movement of calcium into the body. During treatment with prednisolone (20 mg/kg intravenously) for reversal of renal transplant rejection, the serum concentration of calcium decreased and that of iPTH increased. These observations suggest that autonomy of the parathyroid gland rarely occurs in children with renal insufficiency, and that hemodialysis using a dialysate with a high concentration of calcium might assist in retarding the progression of renal osteodystrophy. Furthermore, if hyperparathyroidism contributes in part to growth failure in children with chronic renal disease, steroid-induced changes in cirulating iPTH following renal transplantation may inhibit growth.

  18. Video assisted thoracoscopic excision of mediastinal ectopic parathyroid adenomas: a UK regional experience

    PubMed Central

    Khan, Ali Zamir; Rew, David; Lagattolla, Nicholas; Singh, Neeta

    2015-01-01

    Background To report the first series of video-assisted thoracoscopic surgery (VATS) resection of mediastinal ectopic parathyroid adenomas (MEPAs) in the UK. Methods A case series of seven cases undergoing VATS between 2004 and 2009 to treat single gland hyperparathyroidism. Methylene blue (MB) was used in 5/7 cases immediately before exploration to identify the adenomas. Carbon dioxide (CO2) up to pressures of 10 mmHg was used safely to deflate the lung in two cases. Results There were five women and two men with a mean age of 53 years (range, 27-72 years). Histopathology confirmed successful resection of the parathyroid adenoma in 6/7 cases. There was one conversion to open thoracotomy due to bleeding from the azygos vein resulting from excessive traction. Despite marked MB uptake, this patient proved to have tuberculoid adenopathy and no parathyroid tissue was identified. Postoperative plasma calcium returned to normal in 6/7 patients and parathyroid hormone (PTH) level in 6/7 patients. The median hospital stay was 2 days and there was no mortality in this series. Conclusions MEPAs can be safely resected using VATS with minimal surgical morbidity, short drainage time and short hospital stay. CO2 insufflation and the intraoperative use of MB are safe and help to accurately localise the ectopic adenoma. VATS should be considered as the first-line approach for resection of MEPAs. PMID:26693148

  19. Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts.

    PubMed

    Kim, Sang Wan; Pajevic, Paola Divieti; Selig, Martin; Barry, Kevin J; Yang, Jae-Yeon; Shin, Chan Soo; Baek, Wook-Young; Kim, Jung-Eun; Kronenberg, Henry M

    2012-10-01

    Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing the number of osteoblasts. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 3, 5, 7, 14, and 21. The animals were euthanized on postnatal day 23, 33, or 43 (2, 12, or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (1-34, 80 µg/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of the calvaria and the tibia were flat. Moreover, bone formation rate and collagen I(α1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(α1) mRNA. Electron microscopy revealed X-gal-associated chromogen particles in thin cells prior to PTH administration and in cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo.

  20. The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion.

    PubMed Central

    Brown, A J; Ritter, C R; Finch, J L; Morrissey, J; Martin, K J; Murayama, E; Nishii, Y; Slatopolsky, E

    1989-01-01

    1,25-Dihydroxyvitamin D (1,25-(OH)2D3) directly suppresses the secretion and synthesis of PTH in vivo and in cell culture. This compound has been used to treat secondary hyperparathyroidism associated with renal failure, but in some patients prolonged treatment with 1,25-(OH)2D3 results in hypercalcemia. An analogue of 1,25-(OH)2D3 with little or no calcemic activity, 22-oxacalcitriol (OCT), was recently developed. We confirmed this lack of calcemic activity by acute and chronic administration to normal rats. A single intraperitoneal injection of vehicle (propylene glycol), OCT, or 1,25-(OH)2D3 (1.0 micrograms/rat) increased calcium by 0.32, 0.30, and 1.40 mg/dl, respectively. When rats were given daily injections of vehicle or 0.5 micrograms of either 1,25-(OH)2D3 or OCT for 4 d, calcium did not change in the rats receiving vehicle or OCT, but increased from 8.4 to 11.4 mg/dl in the rats treated with 1,25-(OH)2D3. In primary cultures of bovine parathyroid cells, 10 nM OCT was as active as 10 nM 1,25-(OH)2D3, suppressing PTH release by 33%. This suppression is due, at least in part, to blocking of transcription of the PTH gene. Using a probe prepared by random prime labeling of an Msp I fragment of plasmid PTHm122, we found that a single 40-ng dose of OCT or 1,25-(OH)2D3 depressed PTH mRNA levels by 70-80% by 48 h when compared with vehicle. Thus, OCT is a very effective suppressor of PTH secretion with virtually no calcemic activity. This analogue may be a valuable tool for the treatment of secondary hyperparathyroidism. Images PMID:2760211

  1. Vitamin D deficiency in Korean children: prevalence, risk factors, and the relationship with parathyroid hormone levels

    PubMed Central

    Chung, In Hyuk; Kim, Hae Jung; Chung, Sochung

    2014-01-01

    Purpose This study was performed to investigate the relationship between serum vitamin D and parathyroid hormone (PTH) levels as well as to describe the prevalence and the risk factors of vitamin D deficiency (VDD) in Korean children. Methods Participants were 1,212 children aged 4 to 15 years, who visited Bundang CHA Medical Center (located at 37°N) between March 2012 and February 2013. Overweight was defined as body mass index≥85th percentile. Participants were divided into 4 age groups and 2 seasonal groups. VDD was defined by serum 25-hydroxyvitamin D (25OHD) <20 ng/mL. Results The level of 25OHD was significantly lower in overweight group than in normal weight group (17.1±5.1 ng/mL vs. 19.1±6.1 ng/mL, P<0.001). Winter-spring season (odds ratio [OR], 4.46; 95% confidence interval [CI], 3.45-5.77), older age group (OR, 1.60; 95% CI, 1.36-1.88), and overweight (OR, 2.21; 95% CI, 1.62-3.01) were independently related with VDD. The PTH levels were significantly higher in VDD group compared to vitamin D insufficiency and sufficiency group (P<0.001). In normal weight children, 25OHD (β=-0.007, P<0.001) and ionized calcium (β=-0.594, P=0.007) were independently related with PTH, however, these associations were not significant in overweight children. Conclusion VDD is very common in Korean children and its prevalence increases in winter-spring season, in overweight children and in older age groups. Further investigation on the vitamin D and PTH metabolism according to adiposity is required. PMID:25077091

  2. The Relation Between Variability of Intact Parathyroid Hormone, Calcium, and Cardiac Mortality in Hemodialysis Patients.

    PubMed

    Ulusoy, Sukru; Ozkan, Gulsum; Guvercin, Beyhan; Yavuz, Adnan

    2016-11-01

    Chronic kidney disease-mineral and bone disorder (CKD-BMD) is a condition known to be associated with cardiovascular disease and mortality in hemodialysis (HD) patients. The relation between calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) variability in HD patients and cardiac mortality is unknown. The purpose of this study was to assess the relation between variability in these parameters and cardiac mortality. Baseline demographic and biochemical parameters of 218 HD patients together with Ca values corrected with albumin and P values measured on a monthly basis and iPTH levels measured at 3-monthly intervals were recorded over 2 years. Standard deviation (SD) and smoothness index (SI) for each parameter were calculated to assess Ca, P, and iPTH variability. The relations between all parameters and cardiac mortality were then analyzed. Cardiac mortality was observed in 38 patients in the 2-year study period. Nonsurviving patients' ages, systolic and diastolic blood pressure (DBP), high sensitivity C-reactive protein (HsCRP) levels, mean iPTH, and SD iPTH were significantly higher than those of surviving patients, while albumin levels, SI iPTH and SI Ca were significantly lower. Age, low albumin, high DBP, SI iPTH, and SI Ca were identified as independent predictors of cardiac mortality at multivariate analysis. Our study shows that Ca and iPTH variability affect cardiac mortality independently of mean and baseline values. When supported by further studies, the relation between Ca and iPTH variability and cardiac mortality in HD patients can lead to a new perspective in terms of prognosis and treatment planning.

  3. Genistein modulates the effects of parathyroid hormone in human osteoblastic SaOS-2 cells.

    PubMed

    Chen, Wen-Fang; Wong, Man-Sau

    2006-06-01

    Genistein and parathyroid hormone (PTH) are anabolic agents that stimulate bone formation through their direct actions in osteoblastic cells. In the present study, we aimed to determine whether genistein modulates the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition. The present results showed that genistein (10(-8) to 10(-6) m) induced alkaline phosphatase (ALP) activity and osteoprotegrin (OPG) expression in SaOS-2 cells in a dose-dependent manner. These effects could be completely abolished by co-treatment with oestrogen antagonist ICI 182780 (7alpha-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl]nonyl]-estra-1,3,5(10)-triene-3,17beta-diol). Genistein (at 1 microM) could stimulate the mRNA expression of receptor activator of NF-kappaB ligand (RANKL). As OPG and RANKL are known to modulate osteoclastogenesis, the ability of genistein to modulate OPG and RANKL expression in SaOS-2 cells suggested that it might modulate osteoclastogenesis through its direct actions on osteoblastic cells. PTH (at 10 nM) stimulated ALP activity, induced RANKL mRNA expression and suppressed OPG mRNA expression in SaOS-2 cells, confirming its bi-directional effects on osteoblastic cells. Pre-treatment of SaOS-2 cells with genistein and oestrogen not only enhanced PTH-induced ALP activity, but also attenuated PTH up regulation of RANKL mRNA expression and PTH down regulation of OPG mRNA expression. Taken together, the present study provides the first evidence that genistein could modulate the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition.

  4. Haploinsufficiency of endogenous parathyroid hormone-related peptide impairs bone fracture healing.

    PubMed

    Wang, Yin-He; Qiu, Yong; Han, Xiao-Dong; Xiong, Jin; Chen, Yi-Xin; Shi, Hong-Fei; Karaplis, Andrew

    2013-11-01

    Previous studies have demonstrated that endogenous parathyroid hormone-related peptide (PTHrP) plays a central role in the physiological regulation of bone formation. However, it is unclear whether endogenous PTHrP plays an important function in enhancing bone fracture healing. To determine whether endogenous PTHrP haploinsufficiency impaired bone fracture healing, closed mid-diaphyseal femur fractures were created in 8-week-old wild-type and Pthrp(+/-) mice. Callus tissue properties were analysed 1, 2 and 4 weeks after fracture by radiography, histology, histochemistry, immunohistochemistry and molecular biology. The size of the calluses was reduced 2 weeks after fracture, and the fracture repairs were poor 4 weeks after fractures, in Pthrp(+/-) compared with wild-type mice. Cartilaginous callus areas were reduced 1 week after fracture, but were increased 2 weeks after fracture in Pthrp(+/-) mice. There was a reduction in the number of ostoblasts, alkaline phosphatase (ALP)-positive areas, Type I collagen immunopositive areas, mRNA levels of ALP, Runt-related transcription factor 2 (Runx2) and Type I collagen, Runx2 and insulin-like growth factor-1 protein levels, the number of osteoclasts and the surface in callus tissues in Pthrp(+/-) compared with wild-type mice. These results demonstrate that endogenous PTHrP haploinsufficiency impairs the fracture repair process by reducing cartilaginous and bony callus formation, with downregulation of osteoblastic gene and protein expression and a reduction in endochondral bone formation, osteoblastic bone formation and osteoclastic bone resorption. Together, the results indicate that endogenous PTHrP plays an important role in fracture healing.

  5. Determining the significance of associations between two series of discrete events : bootstrap methods /

    SciTech Connect

    Niehof, Jonathan T.; Morley, Steven K.

    2012-01-01

    We review and develop techniques to determine associations between series of discrete events. The bootstrap, a nonparametric statistical method, allows the determination of the significance of associations with minimal assumptions about the underlying processes. We find the key requirement for this method: one of the series must be widely spaced in time to guarantee the theoretical applicability of the bootstrap. If this condition is met, the calculated significance passes a reasonableness test. We conclude with some potential future extensions and caveats on the applicability of these methods. The techniques presented have been implemented in a Python-based software toolkit.

  6. Vitamin D and parathyroid hormone status in a representative population living in Macau, China.

    PubMed

    Ke, L; Mason, R S; Mpofu, E; Dibley, M; Li, Y; Brock, K E

    2015-04-01

    Associations between documented sun-exposure, exercise patterns and fish and supplement intake and 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were investigated in a random household survey of Macau residents (aged 18-93). Blood samples (566) taken in summer were analyzed for 25OHD and PTH. In this Chinese population, 55% were deficient (25OHD <50nmol/L: median (interquartile range)=47.7 (24.2) nmol/L). Vitamin D deficiency was greatest in those aged <50 years: median (interquartile range)=43.3 (18.2) nmol/L, females: median (interquartile range)=45.5 (19.4) nmol/L and those with higher educational qualifications: median (interquartile range)=43.1 (18.7) nmol/L. In the total Macau population, statistically significant (p<0.01) modifiable associations with lower 25OHD levels were sunlight exposure (β=0.06), physical activity (PA) (measured as hours(hrs)/day: β=0.08), sitting (measured as hrs/day β=-0.20), intake of fish (β=0.08) and calcium (Ca) supplement intake (β=0.06) [linear regression analysis adjusting for demographic risk factors]. On similar analysis, and after adjustment for 25OHD, the only significant modifiable associations in the total population with PTH were sitting (β=-0.17), Body Mass Index (β=0.07) and Ca supplement intake (β=-0.06). In this Macau population less documented sun exposure, fish and Ca supplement intake and exercise were associated with lower 25OHD levels, especially in the younger population, along with the interesting finding that more sitting was associated with both lower 25OHD and high PTH blood levels. In conclusion, unlike findings from Caucasian populations, younger participants were significantly more vitamin D deficient, in particular highly educated single females. This may indicate the desire of young females to be pale and avoid the sun. There are also big differences in lifestyle between the older generation and the younger, in particular with respect to sun exposure and PA. This article is part of

  7. Distribution and regulation of the 25-hydroxyvitamin D3 1α-hydroxylase in human parathyroid glands.

    PubMed

    Ritter, Cynthia S; Haughey, Bruce H; Armbrecht, Harvey J; Brown, Alex J

    2012-05-01

    Parathyroid glands express the 25-hydroxyvitamin D(3) 1α-hydroxylase (1αOHase). 1,25-dihydroxyvitamin D(3) (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)D(3) 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.

  8. Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary Hyperparathyroidism

    PubMed Central

    Komaba, Hirotaka; Nakanishi, Shohei; Fujimori, Akira; Tanaka, Motoko; Shin, Jeongsoo; Shibuya, Koji; Nishioka, Masato; Hasegawa, Hirohito; Kurosawa, Takeshi

    2010-01-01

    Background and objectives: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. Design, setting, participants, & measurements: This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls. Results: Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm3 (group S) and 25 had at least one enlarged gland larger than 500 mm3 (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Conclusions: Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia. PMID:20798251

  9. Dual-phase 99mTc-MIBI imaging findings in sporadic primary hyperplasia of parathyroid glands.

    PubMed

    Yang, Qi-Sheng; Wang, Chang-Yin; Wang, Bi-Cheng

    2015-05-01

    Primary hyperplasia of parathyroid is uncommon and rarely documented in literatures. We report an 18-year-old female patient with hyperparathyroidism due to unifocal primary hyperplasia of parathyroid glands. Dual-phase Tc-MIBI imaging was performed for this patient. We found remarkably increased MIBI uptake in the hyperplastic lesion in early imaging and no extinction of the uptake in delayed imaging. These results suggest that the dual-phase Tc-MIBI imaging is useful in localizing the hyperfunctioning lesions of primary hyperplasia of parathyroid glands.

  10. [Ectopic mediastinal parathyroid tumor resected by video-assisted thoracic surgery with intraoperative methylene blue infusion; report of a case].

    PubMed

    Okagawa, Takehiko; Hiramatsu, Yoshinori

    2014-03-01

    We report a surgical case of ectopic mediastinal parathyroid tumor resected by video-assisted thoracic surgery with intraoperative methylene blue infusion. It is often difficult to detect ectopic mediastinal parathyroid tumor during the operation because the tumor is soft, small and buried under mediastinal tissue. After methylene blue 4 mg/kg intravenously administration, the tumor was gradually dyed blue and easily detected and resected by video-assisted thoracic surgery. It is useful of methylene blue for detection of ectopic mediastinal parathyroid tumor.

  11. Incremental Value of 18F-Fluorocholine PET/CT in the Localization of Double Parathyroid Adenomas.

    PubMed

    Lalire, Paul; Ly, Sang; Deguelte, Sophie; Patey, Martine; Morland, David

    2017-03-01

    A 73-year-old man displaying primary hyperparathyroidism with severe hypercalcemia (Ca: 4.1 mmol/l, PTH > 600 pmol/l) was referred for preoperative localization of a parathyroid adenoma. Tc-pertechnetate and Tc-sestaMIBI dual tracer scintigraphy displayed a mild focal uptake in the projection of the right thyroid lobe with negative ultrasonography. F-Fluorocholine PET/CT was quickly performed considering this discrepancy and not only confirmed the scintigraphic findings but also revealed a second contralateral focus of increased uptake, both later confirmed by operative consideration (the two other parathyroid glands are considered normal by the surgeon), pathology, and intraoperative parathyroid hormone assessment.

  12. Determination of Secondary School Students' Cognitive Structure, and Misconception in Ecological Concepts through Word Association Test

    ERIC Educational Resources Information Center

    Yücel, Elif Özata; Özkan, Mulis

    2015-01-01

    In this study, we determined cognitive structures and misconceptions about basic ecological concepts by using "word association" tests on secondary school students, age between 12-14 years. Eighty-nine students participated in this study. Before WAT was generated, basic ecological concepts that take place in the secondary science…

  13. Determination of Lakeshore Technical Institute Associate Degree Nursing Graduates' Nursing Competencies Level.

    ERIC Educational Resources Information Center

    Schrader, Marvin A.

    In an effort to determine the effectiveness of Lakeshore Technical Institute's (LTI's) Associate Degree Nursing (ADN) program, questionnaires were administered to 1982 program graduates (N=45) and their employers (N=43) requesting an assessment of the graduates' preparedness to perform 39 nursing functions. Responses were submitted to a…

  14. Simultaneous determination of cationic surfactants and nonionic surfactants by ion-association titration.

    PubMed

    Sakai, Tadao; Teshima, Norio; Takatori, Yasufumi

    2003-09-01

    A simultaneous determination of cationic and nonionic surfactants has been developed using ion-association titration. Tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. Benzalkonium reacted with TBPE to form a blue ion-associate in the organic phase. When tetrakis(4-fluorophenyl)borate was added dropwise to the solution, the color of the organic phase turned to yellow at the equivalence point. In addition, when a large amount of potassium ion was added to a solution including Triton X-100, Triton X-100 could be determined by the same technique as described above because of formation of the K+-Triton X-100 cation. The proposed method is available for the stepwise determination of cationic and nonionic surfactants in mixtures.

  15. Modifications of transaxillary approach in endoscopic da Vinci-assisted thyroid and parathyroid gland surgery.

    PubMed

    Al Kadah, Basel; Piccoli, Micaela; Mullineris, Barbara; Colli, Giovanni; Janssen, Martin; Siemer, Stephan; Schick, Bernhard

    2015-03-01

    Endoscopic surgery for treatment of thyroid and parathyroid pathologies is increasingly gaining attention. The da Vinci system has already been widely used in different fields of medicine and quite recently in thyroid and parathyroid surgery. Herein, we report about modifications of the transaxillary approach in endoscopic surgery of thyroid and parathyroid gland pathologies using the da Vinci system. 16 patients suffering from struma nodosa in 14 cases and parathyroid adenomas in two cases were treated using the da Vinci system at the ENT Department of Homburg/Saar University and in cooperation with the Department of General Surgery in New Sant'Agostino Hospital, Modena/Italy. Two different retractors, endoscopic preparation of the access and three different incision modalities were used. The endoscopic preparation of the access allowed us to have a better view during preparation and reduced surgical time compared to the use of a headlamp. To introduce the da Vinci instruments at the end of the access preparation, the skin incisions were over the axilla with one incision in eight patients, two incisions in four patients and three incisions in a further four patients. The two and three skin incisions modality allowed introduction of the da Vinci instruments without arm conflicts. The use of a new retractor (Modena retractor) compared to a self-developed retractor made it easier during the endoscopic preparation of the access and the reposition of the retractor. The scar was hidden in the axilla and independent of the incisions selected, the cosmetic findings were judged by the patients to be excellent. The neurovascular structures such as inferior laryngeal nerve, superior laryngeal nerve and vessels, as well as the different pathologies, were clearly 3D visualized in all 16 cases. No paralysis of the vocal cord was observed. All patients had a benign pathology in their histological examination. The endoscopic surgery of the thyroid and parathyroid gland can be

  16. Self-determination and mental retardation: is there an association with living arrangement and lifestyle satisfaction?

    PubMed

    Duvdevany, I; Ben-Zur, H; Ambar, A

    2002-10-01

    Self-determination and lifestyle satisfaction of 80 adults with mild or medium mental retardation living in group homes or their parents' homes were examined. They were assessed in regard to self-determination, as indicated by choices made in the domestic, financial, health, social, and work domains. Lifestyle satisfaction with residence, the community, associated services, and employment was also assessed. Results show that those from group homes were lower on self-determination but higher on lifestyle satisfaction, providing support for the commitment to normalization and community inclusion to enhance lifestyle satisfaction. However, questions about the extent to which people with mental retardation are afforded decision-making opportunities and self-determined behavior remain. We suggest that service providers and caregivers should encourage and create such opportunities.

  17. A prospective cohort study of novel functional types of parathyroid glands in thyroidectomy: In situ preservation or auto-transplantation?

    PubMed

    Cui, Qiuxia; Li, Zhihua; Kong, Deguang; Wang, Kun; Wu, Gaosong

    2016-12-01

    The best method of preventing hypoparathyroidism after thyroidectomy is to keep parathyroid glands in situ. However, hypoparathyroidism still regularly occurs with the existing parathyroid classification system, and the incidence of permanent hypoparathyroidism has not been reduced. We created a novel system for classifying parathyroid glands that can guide parathyroid preservation in thyroidectomy.We prospectively observed parathyroid glands using the new system in 218 neck surgeries, compared with 132 under the traditional system from January 2014 to September 2015 at a single clinic center. Briefly, we classified parathyroid glands as follows: Type A, no dependency on the thyroid; B1, partial blood supply from the thyroid but retains adequate blood supply after removal of the thyroid; B2, partial blood supply from the thyroid and becomes devascularized after the removal of the thyroid; B3, blood supply mostly from the thyroid; and C, blood supply completely dependent on the thyroid. The classifications were used to decide between in situ preservation or auto-transplantation.The most common type of parathyroid gland was type B1 (53.77%), followed by type A (20.89%), which are the perfect categories for in situ preservation. Type B2 (17.52%) and type B3 (1.21%) have a chance to be kept in situ. For type C (6.61%), in situ preservation is impossible. When in-situ preservation is ruled out, parathyroid auto-transplantation is an alternative, with partial or total gland tissue, depending on the classification and the surgeon's discretion. Among the patients who were classified under the new system, 43.6% presented with transient hypoparathyroidism (symptoms lasting ≤6 months) after surgery, versus 42.4% in the old system, which was not a significant difference. However, permanent hypothyroidism (symptoms lasting >6 months) was not detected in the applied group, but in 3.0% of patients in the nonapplied group (P = 0.01).Our novel functional nomenclature system

  18. Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status

    PubMed Central

    Evans, Sally F.

    2016-01-01

    Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD) was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular) and 2 diaphyseal (mainly cortical)). BMD at femoral neck (FN) and lumbar spine L2–4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH), and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of z and T scores and for biochemical measurements. Results. Low BMD z scores were found at metaphyseal regions in the leg (p < 0.001) and in the FN (p < 0.05). The distal metaphyseal region BMD in the leg was lower than spine or FN (p < 0.05). PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD z scores were associated with body weight (p < 0.02), but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight. PMID:27672477

  19. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto; Takeda, Kan

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  20. MicroRNAs Associated with Caste Determination and Differentiation in a Primitively Eusocial Insect

    PubMed Central

    Collins, David H.; Mohorianu, Irina; Beckers, Matthew; Moulton, Vincent; Dalmay, Tamas; Bourke, Andrew F. G.

    2017-01-01

    In eusocial Hymenoptera (ants, bees and wasps), queen and worker adult castes typically arise via environmental influences. A fundamental challenge is to understand how a single genome can thereby produce alternative phenotypes. A powerful approach is to compare the molecular basis of caste determination and differentiation along the evolutionary trajectory between primitively and advanced eusocial species, which have, respectively, relatively undifferentiated and strongly differentiated adult castes. In the advanced eusocial honeybee, Apis mellifera, studies suggest that microRNAs (miRNAs) play an important role in the molecular basis of caste determination and differentiation. To investigate how miRNAs affect caste in eusocial evolution, we used deep sequencing and Northern blots to isolate caste-associated miRNAs in the primitively eusocial bumblebee Bombus terrestris. We found that the miRNAs Bte-miR-6001-5p and -3p are more highly expressed in queen- than in worker-destined late-instar larvae. These are the first caste-associated miRNAs from outside advanced eusocial Hymenoptera, so providing evidence for caste-associated miRNAs occurring relatively early in eusocial evolution. Moreover, we found little evidence that miRNAs previously shown to be associated with caste in A. mellifera were differentially expressed across caste pathways in B. terrestris, suggesting that, in eusocial evolution, the caste-associated role of individual miRNAs is not conserved. PMID:28361900

  1. MicroRNAs Associated with Caste Determination and Differentiation in a Primitively Eusocial Insect.

    PubMed

    Collins, David H; Mohorianu, Irina; Beckers, Matthew; Moulton, Vincent; Dalmay, Tamas; Bourke, Andrew F G

    2017-03-31

    In eusocial Hymenoptera (ants, bees and wasps), queen and worker adult castes typically arise via environmental influences. A fundamental challenge is to understand how a single genome can thereby produce alternative phenotypes. A powerful approach is to compare the molecular basis of caste determination and differentiation along the evolutionary trajectory between primitively and advanced eusocial species, which have, respectively, relatively undifferentiated and strongly differentiated adult castes. In the advanced eusocial honeybee, Apis mellifera, studies suggest that microRNAs (miRNAs) play an important role in the molecular basis of caste determination and differentiation. To investigate how miRNAs affect caste in eusocial evolution, we used deep sequencing and Northern blots to isolate caste-associated miRNAs in the primitively eusocial bumblebee Bombus terrestris. We found that the miRNAs Bte-miR-6001-5p and -3p are more highly expressed in queen- than in worker-destined late-instar larvae. These are the first caste-associated miRNAs from outside advanced eusocial Hymenoptera, so providing evidence for caste-associated miRNAs occurring relatively early in eusocial evolution. Moreover, we found little evidence that miRNAs previously shown to be associated with caste in A. mellifera were differentially expressed across caste pathways in B. terrestris, suggesting that, in eusocial evolution, the caste-associated role of individual miRNAs is not conserved.

  2. Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study

    SciTech Connect

    Kaplan, M.M.; Boice, J.D. Jr.; Ames, D.B.; Rosenstein, M.

    1988-02-01

    The prevalence of thyroid, parathyroid, and salivary abnormalities was determined in 91 women who received an average of 112 fluoroscopic chest examinations during pneumothorax treatment for tuberculosis more than 40 yr previously and in 72 women treated for tuberculosis by other modalities. Thyroid abnormalities were determined by physical examination, scintiscans, and measurements of serum free T4 index, TSH, and thyroid microsomal antibodies. Thyroid nodules were diagnosed in 7.7% of the exposed and 4.2% of the comparison group (prevalence ratio, 1.8; 90% confidence interval 0.6-5.7). Autoimmune thyroid disease was diagnosed in 15.2% of the exposed and 6.9% of the comparison group (prevalence ratio, 2.2; 95% confidence interval, 0.8-6.2). No salivary tumors were detected. Two exposed women and 1 comparison woman had primary hyperparathyroidism. Although absorbed dose to the thyroid could not be precisely determined, approximately 60 rads would be expected to yield the observed excess of thyroid nodules. While the prevalence ratios were not significantly increased in the exposed group, the results suggest that susceptibility of the thyroid to nodules from cumulative radiation doses of this magnitude could be increased even when the doses are accumulated over years and that such x-ray exposure of the thyroid gland may predispose the patient to the development of autoimmune disease.

  3. A Comparison of Parathyroid Hormone-related Protein (1–36) and Parathyroid Hormone (1–34) on Markers of Bone Turnover and Bone Density in Postmenopausal Women: The PrOP Study

    PubMed Central

    Horwitz, Mara J; Augustine, Marilyn; Kahn, Leila; Martin, Emily; Oakley, Christine C; Carneiro, Raquel M; Tedesco, Mary Beth; Laslavic, Angela; Sereika, Susan M; Bisello, Alessandro; Garcia-Ocaña, Adolfo; Gundberg, Caren M; Cauley, Jane A; Stewart, Andrew F

    2013-01-01

    Parathyroid hormone-related protein (PTHrP)(1–36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but has not been directly compared to parathyroid hormone (PTH)(1–34). We performed a three month, randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis comparing daily subcutaneous injections of PTHrP(1–36) to PTH(1–34). Thirty-five women were randomized to each of three groups: PTHrP(1–36) 400 μg/d; PTHrP(1–36) 600 μg/d; and PTH(1–34) 20 μg/d. The primary outcomes measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2vitamin D and BMD. The increase in bone resorption (CTX) by PTH(1–34) (92%) (p<0.005) was greater than for PTHrP(1–36) (30%) (p<0.05). PTH(1–34) also increased bone formation (PINP) (171%) (p<0.0005) more than either dose of PTHrP(1–36) (46 & 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p<0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1–36) (p<0.05) at the TH, and for PTHrP(1–36) 400 (p<0.05) at the FN. PTHrP(1–36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1–36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1–34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1–36) and PTH(1–34) cause similar increases in LS BMD. PTHrP(1–36) also increased hip BMD. PTH(1–34) induced greater changes in bone turnover than PTHrP(1–36). PTHrP(1–36) was associated with mild transient hypercalcemia. Longer

  4. Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus.

    PubMed

    Yamaguchi, Toru; Kanazawa, Ippei; Takaoka, Shin; Sugimoto, Toshitsugu

    2011-09-01

    Patients with primary hyperparathyroidism have impaired glucose tolerance more often than do controls, and parathyroid resection sometimes improves this derangement. However, it is unclear whether serum calcium (Ca) or parathyroid hormone (PTH) is more strongly related to impaired glucose metabolism in subjects without primary hyperparathyroidism. In this cross-sectional study, we examined patients with type 2 diabetes mellitus (DM) (271 men and 209 women) and analyzed the relationships between serum concentrations of Ca or intact PTH and DM-related variables. Simple regression analyses showed that the level of serum Ca was significantly and positively correlated with the levels of fasting plasma glucose, immunoreactive insulin, and homeostasis model assessment insulin resistance in men (P < .05), but not in women. In contrast, intact PTH was not significantly correlated with DM-related parameters in either sex. Multiple regression analyses showed that the significant and positive correlations between serum Ca vs fasting plasma glucose and homeostasis model assessment insulin resistance in men still remained after adjustment for intact PTH as well as age, body weight, height, creatinine, albumin, phosphate, bone metabolic markers, and estradiol (P < .05). Serum Ca level is positively associated with impaired glucose metabolism, independent of PTH or bone metabolism, in men with type 2 DM.

  5. Relationship between the dimension of parathyroid glands estimated by ultrasonography and the hyperplastic pattern in patients with renal hyperparathyroidism.

    PubMed

    Matsuoka, Susumu; Tominaga, Yoshihiro; Sato, Tetsuhiko; Uno, Nobuaki; Hiramitu, Takahisa; Goto, Norihiko; Nagasaka, Takaharu; Uchida, Kazuharu

    2008-10-01

    In renal hyperparathyroidism (HPT), the parathyroid glands initially proliferate diffusely and polyclonally, and are then transformed to monoclonal nodular hyperplasia with aggressive growth potential. In this study we evaluated the relationship between the maximal dimension of parathyroid glands estimated by ultrasonography (US) and the hyperplastic pattern of parathyroid glands in patients with renal HPT. Between October 1999 and December 2006, 141 patients who underwent total parathyroidectomy (PTx) with forearm autograft in our department were enrolled in this study. In these patients 308 parathyroid glands were detected by US before PTx. The largest dimension of the gland estimated preoperatively by US was correlated closely with its measurement at surgery (R2 was 0.31, P < 0.001). The maximal dimension of diffuse hyperplastic glands was significantly smaller than that of the glands with nodular hyperplastic glands (P < 0.001). There was a strong correlation between the pattern of parathyroid hyperplasia and the glandular diameter when we defined 8 mm as the maximal diameter estimated by US as a cut-off value. As a result of receiver operating characteristic analyses, using these criteria the US technique could predict nodular hyperplasia with a high sensitivity (78.9%) and specificity (78.7%). Parathyroid glands that are enlarged by more than 8 mm in the largest dimension estimated by US may represent glands with nodular hyperplasia.

  6. Food neophobia in German adolescents: Determinants and association with dietary habits.

    PubMed

    Roßbach, Sarah; Foterek, Kristina; Schmidt, Inga; Hilbig, Annett; Alexy, Ute

    2016-06-01

    Food neophobia (FN) is described as the rejection to eat unknown foods. Because only little is known about the role of FN in adolescence the aim of this study was to examine potential determinants of FN and associations with dietary habits of DONALD study participants. FN was measured with Pliner's and Hobden's Food Neophobia Scale (FN Score (FNS): range 10-70) in 166 10-18-year-old adolescents. Participants' age, sex, body weight status and duration of breast-feeding as well as parents' FN and educational status were considered as determinants. Energy intake, distribution of macronutrients and two variety scores were calculated from 3-day weighed dietary records. Multivariable general linear models were performed for data analyses. Boys and girls did not differ in their FNS (median (Min-Max): boys 31 (10-58), girls 32 (14-59)). Increasing age (p = 0.010) and duration of total breast-feeding (p = 0.006) were associated with decreasing FNS in girls only. FN was further positively associated with parental FN in the total sample (p = 0.004). FN was negatively associated with protein intake in the total sample (p = 0.017). The overall low level of FN in the DONALD study can be ascribed to the low level of FN in adolescence in general. Congruently with other studies, age and breast-feeding duration were identified as determinants of girls' FN and parental FN was identified as determinant of FN in the total sample. Further, our results indicate that FN leads to reduced protein intakes. Dietary variety was not strongly affected, possibly because of a broad variety of food supply in Germany.

  7. Determination of equilibrium association constants of ligand-DNA complexes by electrospray mass spectrometry.

    PubMed

    Gabelica, Valérie

    2010-01-01

    Electrospray mass spectrometry can be used to detect ligand-DNA noncovalent complexes formed in solution. This chapter describes how to determine equilibrium association constants of the complexes. Particular attention is devoted to describing how to tune an electrospray mass spectrometer using a 12-mer oligodeoxynucleotides duplex in order to perform these experiments. This protocol can then be applied to any nucleic acid structure that can be ionized with electrospray mass spectrometry.

  8. A Method for and Issues Associated with the Determination of Space Suit Joint Requirements

    NASA Technical Reports Server (NTRS)

    Matty, Jennifer E.; Aitchison, Lindsay

    2010-01-01

    This joint mobility KC lecture included information from two papers, "A Method for and Issues Associated with the Determination of Space Suit Joint Requirements" and "Results and Analysis from Space Suit Joint Torque Testing," as presented for the International Conference on Environmental Systems in 2009 and 2010, respectively. The first paper discusses historical joint torque testing methodologies and approaches that were tested in 2008 and 2009. The second paper discusses the testing that was completed in 2009 and 2010.

  9. Methylene blue and parathyroid adenoma localization: Three new cases of a rare cutaneous complication.

    PubMed

    Lieberman, Elliot D; Thambi, Rakhi; Pytynia, Kristen B

    2016-02-01

    Methylene blue has been safely used for the localization of parathyroid glands during parathyroidectomy, and only a few adverse effects have been documented. Methylene blue administration as a cause of pulse-oximetry-related skin injury is extremely rare. We describe 2 such cases in patients who developed a blister on the second digit at the pulse oximetry site after an uncomplicated excision of a parathyroid adenoma. In another case, a patient became bradycardic intraoperatively; she was successfully resuscitated, but she incurred a second-degree burn at the pulse oximetry site. In all 3 cases, the burns resolved with local wound care. We publish this report to alert surgeons and anesthesiologists to the risk of skin complications with the use of high-dose intraoperative methylene blue.

  10. Determination of absorptivity and formation constant of a chalcone association complex.

    PubMed

    Blanco, S E; Ferretti, F H

    1998-04-01

    A UV spectrometric method was developed to determine the molar absorptivity (epsilon(C)) and formation constant (K(c)) of the association complex of unsubstituted chalcone in cyclohexane, in the concentration range from 4.00.10(-4) to 2.00.10(-2) mol dm(-3). The thermodynamic and spectroscopic magnitudes such as K(c) and epsilon(C) contribute to the understanding of the physicochemical behavior of several alpha,beta-unsaturated carbonylic compounds, of low solubility in water, as it is the case of numerous flavonoids of chemical and biological importance. The studied association complex, formed by two chalcone molecules, is characterized by the constants epsilon(C) (300.8 nm)=4.98.10(4) dm(3) mol(-1) cm(-1) and K(c)=5.58.10(3). The method proposed is convenient for the study of solute-solute molecular associations particularly those due to dipole-dipole interactions.

  11. Association between Bartonella species infection and disease in pet cats as determined using serology and culture.

    PubMed

    Sykes, Jane E; Westropp, Joellen L; Kasten, Rick W; Chomel, Bruno B

    2010-08-01

    This study's objective was to determine whether a relationship exists between infection or seropositivity to Bartonella species and clinical illness in cats. Blood samples were obtained for Bartonella species isolation and immunofluorescent antibody serology from 298 cats presenting to a tertiary referral hospital. Medical records were searched and the history, physical examination findings and the results of diagnostic testing relating to the visit at which Bartonella species testing was performed were recorded. Fifty-two (17%) samples were seropositive for Bartonella henselae, four (1%) for Bartonella clarridgeiae, and 57 (19%) for both organisms. Nineteen (6.4%) samples were culture positive, 17 for B henselae and two for B clarridgeiae. Gingivostomatitis was associated with Bartonella species isolation (P=0.001), but not seropositivity. There was no association with uveitis, neurologic signs, or chronic kidney disease, and a weak association between seropositivity and idiopathic lower urinary tract disease (feline interstitial cystitis) (P=0.05).

  12. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

    PubMed

    Takeuchi, Yasuhiro; Takahashi, Shunsuke; Miura, Daishu; Katagiri, Makoto; Nakashima, Noriaki; Ohishi, Hiroko; Shimazaki, Ryutaro; Tominaga, Yoshihiro

    2016-11-21

    Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

  13. Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.

    PubMed Central

    Naveh-Many, T; Silver, J

    1990-01-01

    In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. Images PMID:2212016

  14. Secretion of sulfated and nonsulfated forms of parathyroid chromogranin A (secretory protein-I)

    SciTech Connect

    Gorr, S.U.; Cohn, D.V. )

    1990-02-25

    Chromogranin A (secretory protein-I) is an acidic, sulfated glycoprotein found in secretory granules of most endocrine cells but not in exocrine or epithelial cells. Parathyroid chromogranin A is sulfated on tyrosine residues, whereas adrenal chromogranin A appears to be sulfated mainly on oligosaccharide residues. Chromogranin B, on the other hand, is tyrosine-sulfated in the bovine adrenal whereas this protein is absent from the parathyroid. The role of this tissue- or species-specific sulfation of chromogranin is not known. Tyrosine sulfation is a common post-translational modification of proteins in the exocytotic pathway and has been suggested to play a role in the sorting or intracellular transport of secretory proteins. To test this, porcine parathyroid tissue slices were metabolically labeled with 35SO4 and (3H)Lys, and the tissue and incubation medium analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and immunoprecipitation with chromogranin A-specific antiserum or by radioimmunoassay for parathormone. Secretion of total and 3H-labeled chromogranin A was about 3- and 7-fold higher, respectively, at 0.5 mM than at 3.0 mM Ca2+, and secretion of 35SO4-labeled chromogranin A was 67-fold higher. This indicates that either sulfated chromogranin A is directed primarily to the Ca2+-regulated pathway or that sulfation occurs following sorting to this pathway. Sodium chlorate (1-10 mM) inhibited sulfation in a dose-dependent manner by up to 95% but it had no effect on the onset or rate of chromogranin A secretion. These data indicate that regulated secretion of parathyroid chromogranin A does not require sulfation of tyrosine residues.

  15. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  16. Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas.

    PubMed

    Dreijerink, Koen M A; Varier, Radhika A; van Nuland, Rick; Broekhuizen, Roel; Valk, Gerlof D; van der Wal, Jacqueline E; Lips, Cornelis J M; Kummer, J Alain; Timmers, H Th Marc

    2009-12-10

    Multiple endocrine neoplasia type 1 (MEN1) is a heriditary syndrome characterised by the occurrence of parathyroid, gastroenteropancreatic and pituitary tumours. The MEN1 gene product, menin, co-activates gene transcription by recruiting histone methyltransferases for lysine 4 of histone H3 (H3K4). We investigated whether in MEN1 tumours global changes in H3K4 trimethylation (H3K4me3) occur or whether alterations in gene expression can be observed. By immunohistochemistry we found that global levels of H3K4me3 are not affected in MEN1-related parathyroid adenomas. Menin can interact directly with the vitamin D receptor (VDR) and enhance the transcriptional activity of VDR. Messenger RNA levels of VDR target genes CYP24 and KLK6 were significantly lower in MEN1 parathyroid adenomas compared to normal tissue. Thus, aberrant gene expression in MEN1 tumours is not caused by lower global H3K4me3, but rather by specific effects on genes that are regulated by menin-interacting proteins, such as VDR.

  17. Intrathyroidal Clear Cell Tumor of Parathyroid Origin with Review of Literature

    PubMed Central

    El Hussein, Siba; Poppiti, Robert; Mesko, Thomas; Manzano, Alex

    2016-01-01

    Water-clear cell adenoma (WCCA) of the parathyroid gland is an exceedingly rare neoplasm. To date, 17 cases have been reported in the literature, with only one of them being intrathyroidal. Here we report a case of a 34-year-old woman who presented for evaluation of a goiter and was found to have a thyroid nodule and abnormal thyroid function tests (TFT). Fine needle aspiration biopsy of the nodule revealed thyroid follicular cells without atypia and subsequent Afirma® Gene Expression Classifier (GEC) testing results were suspicious for malignancy. As a result, the patient underwent a right thyroid lobectomy and isthmusectomy. Histological sections revealed an intrathyroidal nodule consistent with a clear cell neoplasm of parathyroid origin. The histologic appearance together with the immune profile was diagnostic of WCCA, with diffuse positivity for GATA3, focal weak positivity for parathyroid hormone, and negativity for PAX8, thyroglobulin, TTF1, synaptophysin, chromogranin, and S100p. Our study focuses on the clinical presentation, current management strategies, and review of the available literature surrounding this rare diagnosis. The ultimate goal is to help endocrinologists and surgeons establish a foundational treatment plan for intrathyroidal clear cell tumor cases. PMID:28003924

  18. Surgical treatment of primary hyperparathyroidism due to parathyroid tumor: A 15-year experience

    PubMed Central

    Feng, Lu; Zhang, Xu; Liu, Shan-Ting

    2016-01-01

    The aim of this study was to highlight our experience over a 15-year period in dealing with primary hyperparathyroidism (PHPT) due to a parathyroid tumor. Parathyroidectomy is the standard therapy for patients with PHPT. Our study included all patients with PHPT treated by parathyroidectomy at the Affiliated Cancer Hospital of Zhengzhou University, China. Between 1998 and 2013, a total of 107 patients were recruited. Their clinical data, presentation, laboratory examinations, imageological diagnoses and surgical approaches were analyzed retrospectively. Eighty-four cases (78.5%) were followed up. During a median follow-up period of 5.7 years, a total of 80 patients were without recurrence and metastasis. The main symptoms of PHPT patients were palpable neck mass, joint pains and pathological fracture. The high levels of preoperative parathyroid hormone (PTH) and serum calcium in PHPT patients decreased to below the normal upper limit within 3 days of surgery. The sensitivity of neck ultrasonography, sestamibi scanning, CT, MRI and the combination of three or four types of test were 86.0%, 90.4%, 80.8%, 79.6% and 96.1%, respectively. A 50% or greater drop in PTH levels within 20 min compared with the highest PTH levels before surgery occurred in 95/107 cases (88.8%). Transient hypocalcemia was the most common surgical complication. The ultrasonography and sestamibi scan is the most effective examination for parathyroid tumor. The 20 min PTH measurement appears to be extremely useful, and avoids unnecessary bilateral exploration. PMID:27602126

  19. Indices of intact serum parathyroid hormone and renal excretion of calcium, phosphate, and magnesium.

    PubMed Central

    Shaw, N J; Wheeldon, J; Brocklebank, J T

    1990-01-01

    Up to date reference ranges were established for fasting renal excretion of calcium, phosphorus, and magnesium on 101 healthy children aged 2-15 years. A normal range for intact parathyroid hormone was also measured. The indices of calcium and magnesium excretion showed no correlation with age or sex so that a common range for all children could be established. The 97th centile values for urinary calcium:creatinine and magnesium:creatinine ratios were 0.69 mmol:mmol and 1.05 mmol:mmol respectively. The calculated tubular maximum for phosphate/litre of glomerular filtrate (TmPO4/GFR) showed no correlation with age with a geometric mean value of 1.67 mmol/l. The normal range for intact serum parathyroid hormone for the age group was 11-35 ng/l, which is lower than the adult normal range using the same assay. There was an inverse correlation between TmPO4/GFR and intact parathyroid hormone in this group of normal children. PMID:2248530

  20. [Surgical treatment of secondary hyperparathyroidism in chronic kidney failure. Results of total parathyroidectomy with parathyroid autotransplantation].

    PubMed

    Courant, O; Letessier, E; Moutel, M G; Hamy, A; Paineau, J; Visset, J

    1993-01-01

    Between 1978 and 1990, 68 patients, operated on for secondary hyperparathyroidism (HPT), received a forearm intramuscular free autologous parathyroid graft (37 women and 31 men--mean age: 43 +/- 16 years). The transplantation (Wells technique) was performed in the same time as the total parathyroidectomy and the remaining parathyroid material after surgical resection was cryopreserved. The results were evaluated in term of clinical and/or radiological and/or biological response respectively 3 or 5.5 years later, depending of the realisation of a renal transplantation (n = 27) or not. Four patients were lost to follow-up and 4 died post-operatively, including a wrong diagnosis (60 patients evaluated). Mortality rate was 12% (5 cases out of 7 related to chronic renal insufficiency). In 3 patients (5%) the transplanted gland had to be removed because of recurrent HPT (1 graft hyperplasia; 2 wrong diagnosis: 1 cervical gland left over and 1 aluminium intoxication). Second cervicotomy was performed in 3 cases (5%) for remaining cervical parathyroid gland (2 cases) and false-positive Tallium-Technetium scan (1 case). Overall results were good or very good in 51 cases (85%). A review of the literature indicate that subtotal parathyroidectomy in not superior to the Wells technique and the latter remain the landmark technique in the authors' hands in order to treat secondary HPT.

  1. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    SciTech Connect

    Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

    1989-01-01

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release.

  2. Genome-wide association study identifies genetic determinants of urine PCA3 levels in men.

    PubMed

    Chen, Zhuo; Sun, Jielin; Kim, Seong-Tae; Groskopf, Jack; Feng, Junjie; Isaacs, William B; Rittmaster, Roger S; Condreay, Lynn D; Zheng, Siqun Lilly; Xu, Jianfeng

    2013-04-01

    Prostate cancer gene 3 (PCA3) is a non-coding gene specifically overexpressed in prostate cancer (PCa) that has great potential as a clinical biomarker for predicting prostate biopsy outcome. However, genetic determinants of PCA3 expression level remain unknown. To investigate the association between genetic variants and PCA3 mRNA level, a genome-wide association study was conducted in 1371 men of European descent in the REduction by DUtasteride of prostate Cancer Events trial. First-voided urine specimens containing prostate cells were obtained after digital rectal examination. The PROGENSA PCA3 assay was used to determine PCA3 score in the urinary samples. A linear regression model was used to detect the associations between (single nucleotide polymorphisms) SNPs and PCA3 score under an additive genetic model, adjusting for age and population stratification. Two SNPs, rs10993994 in β-microseminoprotein at 10q11.23 and rs10424878 in kallikrein-related peptidase 2 at 19q13.33, were associated with PCA3 score at genome-wide significance level (P = 1.22 x 10(-9) and 1.06 x 10(-8), respectively). Men carrying the rs10993994 "T" allele or rs10424878 "A" allele had higher PCA3 score compared with men carrying rs10993994 "C" allele or rs10424878 "G" allele (β = 1.25 and 1.24, respectively). This is the first comprehensive search for genetic determinants of PCA3 score. The novel loci identified may provide insight into the molecular mechanisms of PCA3 expression as a potential marker of PCa.

  3. Functional analysis of 'a' determinant mutations associated with occult HBV in HIV-positive South Africans.

    PubMed

    Powell, Eleanor A; Boyce, Ceejay L; Gededzha, Maemu P; Selabe, Selokela G; Mphahlele, M Jeffrey; Blackard, Jason T

    2016-07-01

    Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the absence of hepatitis B surface antigen (HBsAg). Occult HBV is associated with the development of hepatocellular carcinoma, reactivation during immune suppression, and virus transmission. Viral mutations contribute significantly to the occult HBV phenotype. Mutations in the 'a' determinant of HBsAg are of particular interest, as these mutations are associated with immune escape, vaccine escape and diagnostic failure. We examined the effects of selected occult HBV-associated mutations identified in a population of HIV-positive South Africans on HBsAg production in vitro. Mutations were inserted into two different chronic HBV backbones and transfected into a hepatocyte-derived cell line. HBsAg levels were quantified by enzyme-linked immunosorbent assay (ELISA), while the detectability of mutant HBsAg was determined using an HA-tagged HBsAg expression system. Of the seven mutations analysed, four (S132P, C138Y, N146D and C147Y) resulted in decreased HBsAg expression in one viral background but not in the second viral background. One mutation (N146D) led to a decrease in HBsAg detected as compared to HA-tag, indicating that this mutation compromises the ability of the ELISA to detect HBsAg. The contribution of occult-associated mutations to the HBsAg-negative phenotype of occult HBV cannot be determined adequately by testing the effect of the mutation in a single viral background, and rigorous analysis of these mutations is required.

  4. Association of a novel preribosomal complex in Trypanosoma brucei determined by fluorescence resonance energy transfer.

    PubMed

    Wang, Lei; Ciganda, Martin; Williams, Noreen

    2013-02-01

    We have previously reported that the trypanosome-specific proteins P34 and P37 form a unique preribosomal complex with ribosomal protein L5 and 5S rRNA in the nucleoplasm. We hypothesize that this novel trimolecular complex is necessary for stabilizing 5S rRNA in Trypanosoma brucei and is essential for the survival of the parasite. In vitro quantitative analysis of the association between the proteins L5 and P34 is fundamental to our understanding of this novel complex and thus our ability to exploit its unique characteristics. Here we used in vitro fluorescence resonance energy transfer (FRET) to analyze the association between L5 and P34. First, we demonstrated that FRET can be used to confirm the association between L5 and P34. We then determined that the binding constant for L5 and P34 is 0.60 ± 0.03 μM, which is in the range of protein-protein binding constants for RNA binding proteins. In addition, we used FRET to identify the critical regions of L5 and P34 involved in the protein-protein association. We found that the N-terminal APK-rich domain and RNA recognition motif (RRM) of P34 and the L18 domain of L5 are important for the association of the two proteins with each other. These results provide us with the framework for the discovery of ways to disrupt this essential complex.

  5. Calcium, parathyroid hormone, oxytocin and pH profiles in the whelping bitch.

    PubMed

    Hollinshead, F K; Hanlon, D W; Gilbert, R O; Verstegen, J P; Krekeler, N; Volkmann, D H

    2010-06-01

    Despite the high prevalence of primary uterine inertia in whelping bitches, the underlying pathogenesis remains unclear. The objectives were to i) determine serum concentrations of total calcium, ionized calcium (iCa), parathyroid hormone (PTH), and blood pH in normally whelping bitches throughout the peri-parturient period; and ii) investigate relationships among iCa, PTH, and acid-base status, and the role that they and oxytocin may have in the underlying pathogenesis of canine uterine inertia. Bitches were randomly selected from a population of German Shepherd Dog bitches with a history of uncomplicated parturition (Group 1; n=10), and from a population of Labrador bitches with a clinical history of an increased incidence of uterine inertia and stillbirths (Group 2; n=20). Jugular blood samples were collected daily from -4 d to the onset of whelping (t=0 h), and then every 4h until the last pup was born. Overall, bitches from Group 2 had higher mean+/-SEM serum concentrations of PTH (4.72+/-2.45 pmol/L, P<0.001), lower iCa (1.31+/-0.08 pmol/L, P<0.05), and higher venous pH (7.41+/-0.03, P<0.005) than bitches from Group 1 (2.9+/-1.44 pmol/L, 1.38+/-0.06 mmol/L, and 7.33+/-0.02, respectively) during the periparturient period. However, there was no significant difference between Groups 1 and 2 for serum oxytocin concentrations during the periparturient period (45.5+/-40 and 65.5+/-82 pg/mL). We inferred that low iCa resulting from a rising pH and decreasing PTH during the periparturient period may have contributed to decreased uterine contractility and increased risk of stillbirths. Therefore, manipulating the cationic/anionic difference in diets of pregnant bitches, similar to the bovine model for hypocalcamia, may reduce the incidence of stillbirths in the bitch.

  6. Association Studies and Legume Synteny Reveal Haplotypes Determining Seed Size in Vigna unguiculata.

    PubMed

    Lucas, Mitchell R; Huynh, Bao-Lam; da Silva Vinholes, Patricia; Cisse, Ndiaga; Drabo, Issa; Ehlers, Jeffrey D; Roberts, Philip A; Close, Timothy J

    2013-01-01

    Highly specific seed market classes for cowpea and other grain legumes exist because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large seeded lines. In this work we applied 1,536-plex SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker-based selection approaches to increase the frequency of progeny with large seed. For 804 individuals derived from eight bi-parental populations, QTL analysis was used to identify markers linked to 10 trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total 10 QTLs were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  7. Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

    PubMed

    Lotito, Ashley; Teramoto, Masaru; Cheung, May; Becker, Kendra; Sukumar, Deeptha

    2017-03-06

    Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH) levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH may differ in overweight and obese adults. We conducted a systematic review and meta-analysis of randomized controlled trials to determine the dose of vitamin D supplementation required to suppress PTH levels in overweight/obese individuals. We identified 18 studies that examined overweight or obese healthy adults who were supplemented with varying doses of vitamin D3. The primary outcomes examined were changes in PTH and serum 25-hydroxyvitamin D (25OHD) levels from baseline to post-treatment. The results of the meta-analysis showed that there was a significant treatment effect of vitamin D supplementation on PTH, total standardized mean difference (SMD) (random effects) = -0.38 (95% CI = -0.56 to -0.20), t = -4.08, p < 0.001. A significant treatment effect of vitamin D supplementation was also found on 25OHD, total SMD (random effects) = 2.27 (95% CI = 1.48 to 3.06) t = 5.62, p < 0.001. Data from available clinical trials that supplemented adults with D3 ranging from 400 IU to 5714 IU, showed that 1000 IU of vitamin D supplementation best suppressed serum PTH levels, total SMD = -0.58, while vitamin D supplementation with 4000 IU showed the greatest increase in serum 25OH levels. Vitamin D and calcium supplementation of 700 IU and 500 mg, respectively, also showed a significant treatment effect on the suppression of PTH with a total SMD = -5.30 (95% CI = -9.72 to -0.88). In conclusion, the meta analysis of available clinical trials indicates that 1000 IU vitamin D supplementation can suppress serum PTH levels, while 4000 IU of vitamin D was associated with the largest increase in serum 25OHD levels in the overweight and obese population.

  8. Serum Parathyroid Hormone Responses to Vitamin D Supplementation in Overweight/Obese Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

    PubMed Central

    Lotito, Ashley; Teramoto, Masaru; Cheung, May; Becker, Kendra; Sukumar, Deeptha

    2017-01-01

    Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH) levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH may differ in overweight and obese adults. We conducted a systematic review and meta-analysis of randomized controlled trials to determine the dose of vitamin D supplementation required to suppress PTH levels in overweight/obese individuals. We identified 18 studies that examined overweight or obese healthy adults who were supplemented with varying doses of vitamin D3. The primary outcomes examined were changes in PTH and serum 25-hydroxyvitamin D (25OHD) levels from baseline to post-treatment. The results of the meta-analysis showed that there was a significant treatment effect of vitamin D supplementation on PTH, total standardized mean difference (SMD) (random effects) = −0.38 (95% CI = −0.56 to −0.20), t = −4.08, p < 0.001. A significant treatment effect of vitamin D supplementation was also found on 25OHD, total SMD (random effects) = 2.27 (95% CI = 1.48 to 3.06) t = 5.62, p < 0.001. Data from available clinical trials that supplemented adults with D3 ranging from 400 IU to 5714 IU, showed that 1000 IU of vitamin D supplementation best suppressed serum PTH levels, total SMD = −0.58, while vitamin D supplementation with 4000 IU showed the greatest increase in serum 25OH levels. Vitamin D and calcium supplementation of 700 IU and 500 mg, respectively, also showed a significant treatment effect on the suppression of PTH with a total SMD = −5.30 (95% CI = −9.72 to −0.88). In conclusion, the meta analysis of available clinical trials indicates that 1000 IU vitamin D supplementation can suppress serum PTH levels, while 4000 IU of vitamin D was associated with the largest increase in serum 25OHD levels in the overweight and obese population. PMID

  9. Relative weight of glucose, insulin and parathyroid hormone in the urinary loss of phosphate by chronically diabetic rats.

    PubMed

    Locatto, M E; Di Loreto, V; Fernández, M C; Caferra, D; Puche, R C

    1997-10-01

    This report deals with the relationships between glucose (G) and insulin on the tubular transport of phosphate (P) in chronically diabetic rats with high plasma levels of parathyroid hormone (PTH). Alloxan-induced diabetes leads to phosphorus depletion of the soft tissues. This phenomenon appears associated with weight loss and negative P balances caused by the increased urinary P excretion. Administration of 2 IU of insulin/100 g body weight (bw) to diabetic rats normalized their P balance and body weight. The effect of parathyroid function on the P metabolism of diabetic rats was investigated with balance experiments. Diabetic rats, intact or thyroparathyroidectomized (TPTX), have a greater urinary excretion of P than their controls. However, in control rats, the ratio intact:TPTX for urinary P is 1.0:0.76, showing the antiphosphaturic effect of parathyroid ablation. For diabetic animals, on the other hand, the ratio is 1.0:1.44. The simultaneous deficit of insulin and PTH thus quadruples the urinary P loss, instead of compensating for each other. The contribution of insulin deficit and hyperglycemia to the defect in tubular reabsorption (TRP) was investigated with clearance experiments (done on anesthetized, perfused rats). Five experimental groups were used: Controls (C), diabetics (D), controls + glucose (C + G), diabetics + insulin (D + I) and diabetics + insulin + glucose (D + I + G). All experimental groups showed a linear relationship between the TRP of P and G. The regression equation for C is significantly different (F = 40.1, P < 0.001) from that of D animals. The slope value measure the number of mumoles of P per mumol of G reabsorbed. For C and D rats, the ratio P:G approximates 1:4 and 1:20, respectively. The increase in P:G ratios represents the competition between both substrates for tubular resorption. Glycemias up to 11 mM (C and D + I) exist concurrent with the P:G ratio 1:4 Glycemias above 25 mM (D, C + G and D + I + G) produce a P:G ratio of 1

  10. Stepwise determination of quaternary ammonium salts and aromatic amines in pharmaceuticals by ion association titration.

    PubMed

    Sakai, T

    2001-12-01

    A stepwise titrimetric method has been developed for the simultaneous determination of pharmaceutical quaternary ammonium salts (R4N+) and aromatic amines (R3N). The method is based on the solvent extraction of R4N+ and R3NH+ with an ion association reagent. Sodium tetrakis(4-fluorophenyl)borate and sodium tetraphenylborate were used as titrants and potassium tetrabromophenolphthalein ethyl ester (TBPE) was used as an indicator. The ion associate which formed between R4N+ ion and TBPE made a blue color in 1,2-dichloroethane, while the ion associate formed between R3NH+ and TBPE showed a red-violet one. Sample solutions containing quaternary ammonium and/or amine compounds were titrated with sodium tetrakis(4-fluorophenyl)borate or sodium tetraphenylborate. When one drop of excess titrant was added, the color of the organic phase turned from blue or red-violet to yellow at the equivalence point. On the other hand, in the mixture of R4N+ and R3N, the color changed from blue to red-violet at the first equivalence point, and then its color turned to yellow at the second equivalence point. The quaternary ammonium compound and aromatic amine in pharmaceuticals could be simultaneously and successfully determined by the proposed titration method.

  11. Determining the Incidence of Drug-Associated Acute Kidney Injury in Nursing Home Residents

    PubMed Central

    Handler, Steven M.; Cheung, Pui Wen; Culley, Colleen M.; Perera, Subashan; Kane-Gill, Sandra L.; Kellum, John A.; Marcum, Zachary A.

    2015-01-01

    Objective Although acute kidney injury (AKI) is well-studied in the acute care setting, investigation of AKI in the nursing home (NH) setting is virtually nonexistent. The goal of this study was to determine the incidence of drug-associated AKI using the RIFLE (Risk, Injury, Failure, Loss of kidney function or End-Stage kidney disease) criteria in NH residents. Design/Setting/Participants/Measurements We conducted a retrospective study between February 9, 2012 and February 8, 2013 for all residents at four UPMC NHs located in Southwest Pennsylvania. The TheraDoc™ Clinical Surveillance System, which monitors laboratory and medication data and fires alerts when patients have a sufficient increase in serum creatinine, was used for automated case detection. An increase in serum creatinine in the presence of an active medication order identified to potentially cause AKI triggered an alert, and drug-associated AKI was staged according to the RIFLE criteria. Data were analyzed by frequency and distribution of alert type by risk, injury, and failure. Results Of the 249 residents who had a drug-associated AKI alert fire, 170 (68.3%) were female, and the mean age was 74.2 years. Using the total number of alerts (n=668), the rate of drug-associated AKI was 0.35 events per 100 resident-months. Based on the RIFLE criteria, there were 191, 70, and 44 residents who were classified as AKI risk, injury, and failure, respectively. The most common medication classes included in the AKI alerts were diuretics, ACEIs/ARBs, and antibiotics. Conclusion Drug-associated AKI was a common cause of potential adverse drug events. The vast majority of the cases were related to the use of diuretics, ACEIs/ARBs and antibiotics. Future studies are needed to better understand patient, provider and facility risk factors as well as strategies to enhance the detection and management of drug-associated AKI in the NH. PMID:24814042

  12. A Co-Association Network Analysis of the Genetic Determination of Pig Conformation, Growth and Fatness

    PubMed Central

    Puig-Oliveras, Anna; Ballester, Maria; Corominas, Jordi; Revilla, Manuel; Estellé, Jordi; Fernández, Ana I.; Ramayo-Caldas, Yuliaxis; Folch, Josep M.

    2014-01-01

    Background Several QTLs have been identified for major economically relevant traits in livestock, such as growth and meat quality, revealing the complex genetic architecture of these traits. The use of network approaches considering the interactions of multiple molecules and traits provides useful insights into the molecular underpinnings of complex traits. Here, a network based methodology, named Association Weight Matrix, was applied to study gene interactions and pathways affecting pig conformation, growth and fatness traits. Results The co-association network analysis underpinned three transcription factors, PPARγ, ELF1, and PRDM16 involved in mesoderm tissue differentiation. Fifty-four genes in the network belonged to growth-related ontologies and 46 of them were common with a similar study for growth in cattle supporting our results. The functional analysis uncovered the lipid metabolism and the corticotrophin and gonadotrophin release hormone pathways among the most important pathways influencing these traits. Our results suggest that the genes and pathways here identified are important determining either the total body weight of the animal and the fat content. For instance, a switch in the mesoderm tissue differentiation may determinate the age-related preferred pathways being in the puberty stage those related with the miogenic and osteogenic lineages; on the contrary, in the maturity stage cells may be more prone to the adipocyte fate. Hence, our results demonstrate that an integrative genomic co-association analysis is a powerful approach for identifying new connections and interactions among genes. Conclusions This work provides insights about pathways and key regulators which may be important determining the animal growth, conformation and body proportions and fatness traits. Molecular information concerning genes and pathways here described may be crucial for the improvement of genetic breeding programs applied to pork meat production. PMID:25503799

  13. Can the Transport Properties of Molten Salts and Ionic Liquids Be Used To Determine Ion Association?

    PubMed

    Harris, Kenneth R

    2016-12-01

    There have long been arguments supporting the concept of ion association in molten salts and ionic liquids, largely based on differences between the conductivity and that predicted from self-diffusion coefficients by the Nernst-Einstein equation for noninteracting ions. It is known from molecular dynamics simulations that even simple models based on charged hard spheres show such a difference due to the (anti)-correlation of ion motions. Formally this is expressed as a difference between the velocity cross-correlation coefficient of the oppositely charged ions and the mean of those for the two like-charged ions. This article examines molten salt and ionic liquid transport property data, comparing simple and model associated salts (ZnCl2, PbCl2, and TlCl) including weakly dissociated molecular liquids (H2O, HCOOH, H2SO4). Analysis employing Laity resistance coefficients (rij) shows that the common ion-association rationalization is flawed, consistent with recent direct measurements of the degree of ionicity in ionic liquid chlorides and with theoretical studies. However, the protic ionic liquids [PyrOMe][BF4] and [DBUH][CH3SO3] have larger than usual NE deviation parameters (>0.5), and large negative like-ion rii, analogous to those of ZnCl2. Structural, spectroscopic, and theoretical studies are suggested to determine whether these are indeed genuine examples of association.

  14. A Review of Hypothesized Determinants Associated with Bighorn Sheep (Ovis canadensis) Die-Offs

    PubMed Central

    Miller, David S.; Hoberg, Eric; Weiser, Glen; Aune, Keith; Atkinson, Mark; Kimberling, Cleon

    2012-01-01

    Multiple determinants have been hypothesized to cause or favor disease outbreaks among free-ranging bighorn sheep (Ovis canadensis) populations. This paper considered direct and indirect causes of mortality, as well as potential interactions among proposed environmental, host, and agent determinants of disease. A clear, invariant relationship between a single agent and field outbreaks has not yet been documented, in part due to methodological limitations and practical challenges associated with developing rigorous study designs. Therefore, although there is a need to develop predictive models for outbreaks and validated mitigation strategies, uncertainty remains as to whether outbreaks are due to endemic or recently introduced agents. Consequently, absence of established and universal explanations for outbreaks contributes to conflict among wildlife and livestock stakeholders over land use and management practices. This example illustrates the challenge of developing comprehensive models for understanding and managing wildlife diseases in complex biological and sociological environments. PMID:22567546

  15. TRPV4 associates environmental temperature and sex determination in the American alligator

    PubMed Central

    Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Saito, Shigeru; Lowers, Russell H.; Ogino, Yukiko; Fukuta, Naomi; Katsu, Yoshinao; Ohta, Yasuhiko; Tominaga, Makoto; Guillette Jr, Louis J.; Iguchi, Taisen

    2015-01-01

    Temperature-dependent sex determination (TSD), commonly found among reptiles, is a sex determination mode in which the incubation temperature during a critical temperature sensitive period (TSP) determines sexual fate of the individual rather than the individual’s genotypic background. In the American alligator (Alligator mississippiensis), eggs incubated during the TSP at 33 °C (male producing temperature: MPT) yields male offspring, whereas incubation temperatures below 30 °C (female producing temperature: FPT) lead to female offspring. However, many of the details of the underlying molecular mechanism remains elusive, and the molecular link between environmental temperature and sex determination pathway is yet to be elucidated. Here we show the alligator TRPV4 ortholog (AmTRPV4) to be activated at temperatures proximate to the TSD-related temperature in alligators, and using pharmacological exposure, we show that AmTRPV4 channel activity affects gene expression patterns associated with male differentiation. This is the first experimental demonstration of a link between a well-described thermo-sensory mechanism, TRPV4 channel, and its potential role in regulation of TSD in vertebrates, shedding unique new light on the elusive TSD molecular mechanism. PMID:26677944

  16. TRPV4 associates environmental temperature and sex determination in the American alligator.

    PubMed

    Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Saito, Shigeru; Lowers, Russell H; Ogino, Yukiko; Fukuta, Naomi; Katsu, Yoshinao; Ohta, Yasuhiko; Tominaga, Makoto; Guillette, Louis J; Iguchi, Taisen

    2015-12-18

    Temperature-dependent sex determination (TSD), commonly found among reptiles, is a sex determination mode in which the incubation temperature during a critical temperature sensitive period (TSP) determines sexual fate of the individual rather than the individual's genotypic background. In the American alligator (Alligator mississippiensis), eggs incubated during the TSP at 33 °C (male producing temperature: MPT) yields male offspring, whereas incubation temperatures below 30 °C (female producing temperature: FPT) lead to female offspring. However, many of the details of the underlying molecular mechanism remains elusive, and the molecular link between environmental temperature and sex determination pathway is yet to be elucidated. Here we show the alligator TRPV4 ortholog (AmTRPV4) to be activated at temperatures proximate to the TSD-related temperature in alligators, and using pharmacological exposure, we show that AmTRPV4 channel activity affects gene expression patterns associated with male differentiation. This is the first experimental demonstration of a link between a well-described thermo-sensory mechanism, TRPV4 channel, and its potential role in regulation of TSD in vertebrates, shedding unique new light on the elusive TSD molecular mechanism.

  17. Zfp521 Is a Target Gene and Key Effector of Parathyroid Hormone-Related Peptide Signaling in Growth Plate Chondrocytes

    PubMed Central

    Correa, Diego; Hesse, Eric; Seriwatanachai, Dutmanee; Kiviranta, Riku; Saito, Hiroaki; Yamana, Kei; Neff, Lynn; Atfi, Azeddine; Coillard, Lucie; Sitara, Despina; Maeda, Yukiko; Warming, Soren; Jenkins, Nancy A.; Copeland, Neal G.; Horne, William C.; Lanske, Beate; Baron, Roland

    2010-01-01

    Summary In the growth plate, the interplay between Parathyroid Hormone-Related Peptide (PTHrP) and Indian Hedgehog (Ihh) signaling tightly regulates chondrocyte proliferation and differentiation during longitudinal bone growth. We found that PTHrP increases the expression of Zfp521, a zinc finger transcriptional co-regulator, in pre-hypertrophic chondrocytes. Mice with chondrocyte-targeted deletion of Zfp521 resembled PTHrP-/- and chondrocyte-specific PTHR1-/- mice, with decreased chondrocyte proliferation, early hypertrophic transition and reduced growth plate thickness. Deleting Zfp521 increased expression of Runx2 and Runx2 target genes, and decreased cyclin D1 and Bcl-2 expression while increasing caspase-3 activation and apoptosis. Zfp521 associated with Runx2 in chondrocytes, antagonizing its activity via an HDAC4-dependent mechanism. PTHrP failed to up-regulate cyclin D1 and to antagonize Runx2, Ihh and Collagen X expression when Zfp521 was absent. Thus, Zfp521 is an important PTHrP target gene that regulates growth plate chondrocyte proliferation and differentiation. PMID:20951345

  18. Acute-onset hypomagnesemia-induced hypocalcemia caused by the refractoriness of bones and renal tubules to parathyroid hormone.

    PubMed

    Yamamoto, Masahiro; Yamaguchi, Toru; Yamauchi, Mika; Yano, Shozo; Sugimoto, Toshitsugu

    2011-11-01

    Chronic hypomagnesemia is closely associated with hypocalcemia, which is caused by impaired parathyroid hormone (PTH) secretion or the refractoriness of bone and renal tubules to PTH. The dominant mechanism of acute-onset, hypomagnesemia-induced hypocalcemia is currently unclear. An 83-year-old man who had undergone chemotherapy with carboplatin for prostate cancer suffered from acute diarrhea and finger paresthesia. Laboratory data confirmed hypocalcemia as well as hypomagnesemia. Urinary calcium levels were not measured. However, the urinary fractional excretion of Mg (FE(Mg)) was elevated. Despite elevated PTH levels, the renal tubular maximal reabsorption rate of phosphate to GFR (TmP/GFR) was elevated, and bone formation and resorption markers were suppressed. A magnesium loading test revealed a clear magnesium deficiency. After administration of magnesium, bone marker levels were increased, and TmP/GFR was reduced to normal levels, despite the persistent elevation of PTH. Serum calcium levels eventually increased to approximately the reference range. Clinical histories and these observations both suggest that when patients with hypomagnesemia-induced hypocalcemia rapidly lose magnesium through complications such as diarrhea, the primary cause may be the refractoriness of bone and renal tubules to PTH, rather than impaired PTH secretion.

  19. A case report on acute severe hyponatraemia following parathyroid surgery for primary hyperparathyroidism—A rare but life threatening complication

    PubMed Central

    Hillary, S.L.; Hemead, H.; Berthoud, M.; Balasubramanian, S.P.

    2016-01-01

    Introduction Parathyroidectomy is a common operation, which is well tolerated and associated with low morbidity. Patients are usually discharged within 24 hours of surgery. Severe postoperative hyponatraemia is a rare complication which can cause significant morbidity including seizure, coma, respiratory arrest and even death. Presentation of case We present two patients with clinically significant hyponatremia resulting in seizures and collapse within 24 hours after parathyroidectomy, an unreported complication following surgery for primary hyperparathyroidism. One patient required support on the High Dependency Unit and both were treated with fluid restriction which resulted in correction of their electrolyte balance. Discussion We believe this was caused by the relative inability to secrete a water load after surgery and non-psychogenic polydipsia. Preoperatively, neither patient was prescribed any routine medications nor did they have any risk factors for hyponatremia. Both had normal preoperative sodium levels. It is usual practice is to advise patients to increase oral water intake when they are hypercalcaemic. The aim of parathyroidectomy is to treat hypercalcaemia by stopping excess PTH secretion from abnormal parathyroid glands. These patients continued to follow this advice after surgery when they were eucalcaemic after their operation and because they were thirsty. The patients drank several litres of water in 12–24 hours after surgery. We believe that this may have contributed to this complication. Conclusion Healthcare professionals need to be aware of this complication and patients should be advised to restrict intake of free water after surgery. PMID:26994458

  20. Comparison of calcium effect on in vitro calcitonin and parathyroid hormone release by young and aged thyroparathyroid glands.

    PubMed

    Wongsurawat, N; Armbrecht, H J

    1987-01-01

    Serum immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) levels are higher in young than aged rats. However, serum calcium concentration does not change with age suggesting that the calcium regulation of PTH and CT secretion may be affected by aging. We compared iPTH and iCT secretion in vitro at low and high calcium concentrations using thyroparathyroid glands removed from young (2-3 months), adult (12-13 months), and old (24-27 months) F-344 male rats fed regular rat chow. Glands from each animal were incubated for 3 h in serum-free culture media containing 1.0 mM calcium and then transferred to media containing 2.5 mM calcium for another 3 h. Immunoreactive PTH and iCT concentrations of the media after each incubation period were determined by radioimmunoassay. Immunoreactive PTH and iCT secretion per pair of glands was significantly higher in glands from older animals regardless of calcium concentration. The decrease in iPTH, and increment in iCT, secretion in response to 2.5 mM calcium by glands from old rats was smaller than that observed for glands from young animals. These age-related changes in the regulation of secretion by calcium may contribute to the increased iPTH and iCT secretion and serum levels seen in older animals.

  1. Association of bone mineral density with polymorphism of the human calcium-sensing receptor locus.

    PubMed

    Tsukamoto, K; Orimo, H; Hosoi, T; Miyao, M; Ota, N; Nakajima, T; Yoshida, H; Watanabe, S; Suzuki, T; Emi, M

    2000-03-01

    A strong correlation between bone mass and genetic factors has been shown in twins and family studies. Some of the genes involved would regulate bone metabolism, bone formation, and resorption, all processes that determine bone mass. One candidate genes, calcium-sensing receptor (CASR) in the parathyroid gland, regulates calcium homeostasis by sensing decreases in extracellular calcium level and effecting an increase in secretion of parathyroid hormone (PTH) and calcium (Ca) reabsorption in the kidney. We have investigated a possible association between the CA-repeat polymorphism at the human CASR gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into nine groups according to the number of CA repeats present, from 20 to 12. BMD was expressed as the adjusted BMD, which was the body mass index (BMI), and age-adjusted average BMD. The 247 women who had an A3 allele (228 bp, containing 18 repeats of CA) had significantly lower adjusted BMD (mean +/- SD: 0.303 +/- 0.059 versus 0.316 +/- 0.063 g/cm(2); P = 0.0308) than the participants (n = 201) who did not carry an allele of that size. This result suggests that genetic variation at the CASR gene locus is associated with some determinants for BMD in postmenopausal women.

  2. Studies on the antigenic determinants in the self-association of IgG rheumatoid factor

    PubMed Central

    Nardella, FA; Teller, DC; Mannik, M

    1981-01-01

    The number, location, and other characteristics of the antigenic determinants for self-association of IgG-rheumatoid factors (IgG-RF) were examined using the IgG-RF isolated from the plasma of one patient as a model system. Affinity chromatography was employed for isolation of the IgG-RF. Sedimentation equilibrium ultracentrifugation was used to study the various interactions. The antigenic valence of IgG-RF Fc, normal human Fc, and rabbit Fc fragments was two for the interaction with Fab fragments from IgG-RF, as might be expected from the molecular symmetry of IgG. The antigenic valence of intact normal IgG, however, was only one, indicating that when one of the available antigenic determinants interacted with the Fab fragment of IgG-RF, the other determinant becomes sterically inaccessible. Reduction and alkylation, known to increase the flexibility of the hinge region, did not alter the antigenic valence of IgG for Fab fragments of IgG-RF. The antigenic valence of IgG-RF in self-association could not be experimentally determined but must be two to permit the observed concentration-dependent further polymer formation of IgG-RF dimers. Unique antigenic determinants on the Fc fragments of IgG-RF were sought and not found, thus reaffirming the formation of two antigen-antibody bonds as the basis for dimerization of IgG-RF molecules. The pFc’ and Fc’ fragments, representing Cγ3 domains of IgG, failed to show significant interaction with Fab fragments of IgG-RF, indicating that the antigenic determinants were not expressed by the Cγ3 regions but are located either on Cγ2 region or require intact Cγ2 and Cγ3 regions for expression. These conclusions were corroborated by the antigenic valence of one for the Fc(i) fragment, a new papain-generated intermediate fragment of Fc, composed of two intact Cγ3 domains and one intact Cγ2 domain. Normal IgG, because of its valence of one for interaction with IgG-RF, would effectively terminate further polymerization of

  3. Determination of Cancer Risk Associated with Germ Line BRCA1 Missense Variants by Functional Analysis

    PubMed Central

    Carvalho, Marcelo A.; Marsillac, Sylvia M.; Karchin, Rachel; Manoukian, Siranoush; Grist, Scott; Swaby, Ramona F.; Urmenyi, Turan P.; Rondinelli, Edson; Silva, Rosane; Gayol, Luis; Baumbach, Lisa; Sutphen, Rebecca; Pickard-Brzosowicz, Jennifer L.; Nathanson, Katherine L.; Sali, Andrej; Goldgar, David; Couch, Fergus J.; Radice, Paolo; Monteiro, Alvaro N.A.

    2010-01-01

    Germ line inactivating mutations in BRCA1 confer susceptibility for breast and ovarian cancer. However, the relevance of the many missense changes in the gene for which the effect on protein function is unknown remains unclear. Determination of which variants are causally associated with cancer is important for assessment of individual risk. We used a functional assay that measures the transactivation activity of BRCA1 in combination with analysis of protein modeling based on the structure of BRCA1 BRCT domains. In addition, the information generated was interpreted in light of genetic data. We determined the predicted cancer association of 22 BRCA1 variants and verified that the common polymorphism S1613G has no effect on BRCA1 function, even when combined with other rare variants. We estimated the specificity and sensitivity of the assay, and by meta-analysis of 47 variants, we show that variants with <45% of wild-type activity can be classified as deleterious whereas variants with >50% can be classified as neutral. In conclusion, we did functional and structure-based analyses on a large series of BRCA1 missense variants and defined a tentative threshold activity for the classification missense variants. By interpreting the validated functional data in light of additional clinical and structural evidence, we conclude that it is possible to classify all missense variants in the BRCA1 COOH-terminal region. These results bring functional assays for BRCA1 closer to clinical applicability. PMID:17308087

  4. Colorimetric determination of sildenafil citrate (Viagra) through ion-associate complex formation.

    PubMed

    Amin, Alaa S; Moustafa, Moustafa E; El-Dosoky, Reham

    2009-01-01

    A simple, quick, accurate, and sensitive colorimetric method is described for the determination of sildenafil citrate (SLD). The method is based on the reaction of SLD with Congo Red, Sudan II, and Gentian Violet in buffered aqueous solutions at pH 2.5, 6.5, and 11.0, respectively, to give highly colored soluble ion-associate complex species; the colored products are quantitated colorimetrically at 523, 554, and 569 nm, respectively. The various experimental conditions were optimized. The stoichiometric ratio was found to be 1:1 for all ion associates; the calculated logarithmic stability constants were 8.51, 7.79, and 5.58, respectively. Beer's law was obeyed over the concentration range of 0.2-7.0 microg/mL, whereas the Ringbom optimum concentration range was 0.4-6.5 microg/mL. Values for molar absorptivity, Sandell sensitivity, and detection and quantification limits were also calculated. The proposed method was successfully applied to the determination of SLD in Viagra tablets and in serum samples by using the technique of standard additions with mean accuracy values of 100.06 +/- 1.14, 99.87 +/- 0.70, and 99.86 +/- 0.97% for Viagra tablets and 99.88 +/- 0.60, 99.90 +/- 0.90, and 100.24 +/- 0.80% for serum samples, respectively.

  5. First evidence of TRPV5 and TRPV6 channels in human parathyroid glands: possible involvement in neoplastic transformation.

    PubMed

    Giusti, Laura; Cetani, Filomena; Da Valle, Ylenia; Pardi, Elena; Ciregia, Federica; Donadio, Elena; Gargini, Claudia; Piano, Ilaria; Borsari, Simona; Jaber, Ali; Caputo, Antonella; Basolo, Fulvio; Giannaccini, Gino; Marcocci, Claudio; Lucacchini, Antonio

    2014-10-01

    The parathyroid glands play an overall regulatory role in the systemic calcium (Ca(2+)) homeostasis. The purpose of the present study was to demonstrate the presence of the Ca(2+) channels transient receptor potential vanilloid (TRPV) 5 and TRPV6 in human parathyroid glands. Semi-quantitative and quantitative PCR was carried out to evaluate the presence of TRPV5 and TRPV6 mRNAs in sporadic parathyroid adenomas and normal parathyroid glands. Western blot and immunocytochemical assays were used to assess protein expression, cellular localization and time expression in primary cultures from human parathyroid adenoma. TRPV5 and TRPV6 transcripts were then identified both in normal and pathological tissues. Predominant immunoreactive bands were detected at 75-80 kD for both vanilloid channels. These channels co-localized with the calcium-sensing receptor (CASR) on the membrane surface, but immunoreactivity was also detected in the cytosol and around the nuclei. Our data showed that western blotting recorded an increase of protein expression of both channels in adenoma samples compared with normal glands suggesting a potential relation with the cell calcium signalling pathway and the pathological processes of these glands.

  6. Genetic determinants of cardiometabolic risk: a proposed model for phenotype association and interaction.

    PubMed

    Blackett, Piers R; Sanghera, Dharambir K

    2013-01-01

    This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes, and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus, it follows that the genetics of dyslipidemia, obesity, and nonalcoholic fatty liver disease are central in triggering progression of the syndrome to overt expression of disease traits and have become a key focus of interest for early detection and for designing prevention and treatments. To support the "birds' eye view" approach, we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacologic targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance.

  7. Influence of the dosing frequency of parathyroid hormone-(1-38) on its anabolic effect in bone and on the balance of calcium, phosphorus and magnesium.

    PubMed

    Riond, J L; Goliat-von Fischer, I; Küffer, B; Toromanoff, A; Forrer, R

    1998-06-01

    The effect of the frequency of administration of synthetic human parathyroid hormone fragment 1-38 [hPTH-(1-38)] on bone formation and on the balance of calcium, phosphorus, and magnesium was investigated in 32 9-week-old female Sprague-Dawley rats, using a randomly complete block design. Rats received subcutaneously during 14 days either the vehicle solution once a day or 50 micrograms hPTH-(1-38)/kg BW once a day at 8:00 a.m., twice a day at 8:00 a.m. and 5:00 p.m. or three times a day at 8:00 a.m., 0:30 p.m., and 5:00 p.m. The balance study was performed during the last 48 h of the hPTH-(1-38) treatment schedule after which femora, tibiae, and lumbar vertebrae were removed for the determination of the dry weight, volume, and contents of Ca, P, Mg, hydroxyproline, and DNA. PTH treatment was associated with a significant increase of the apparent intestinal absorption of Ca, P, and Mg. Mean urinary Ca excretion augmented with the increase of the frequency of dosing. Urinary Ca excretion correlated negatively with the Ca apparent intestinal absorption and with the Ca content of the tibiae in the 2 groups with the highest frequency of dosing. The mean Ca, P, and Mg balances, the mean contents of bone Ca, P, and Mg and the mean bone dry weights were significantly increased with PTH treatment. In contrast to the mean volume of tibiae which was not affected by the PTH administration, the mean volume of the fifth lumbar vertebrae increased with the treatment. With the 2 times and 3 times daily treatments, mean hydroxyproline concentrations in the femora were significantly higher than the control values. An increase of the mean hydroxyproline content of the third lumbar vertebrae was evidenced with the 1 time and 2 times daily treatment, but the mean of the highest frequency of dosing was not different from that of the control group. The DNA content of femoral and of the fourth lumbar vertebrae significantly decreased with the frequency of dosing.

  8. The serum level of 25-hydroxyvitamin D for maximal suppression of parathyroid hormone in children: the relationship between 25-hydroxyvitamin D and parathyroid hormone

    PubMed Central

    Kang, Jung In; Lee, Yoon Suk; Han, Ye Jin; Kong, Kyoung Ae

    2017-01-01

    Purpose Serum level of 25-hydroxyvitamin D (25-OHD) is considered as the most appropriate marker of vitamin D status. However, only a few studies have investigated the relationship between 25-OHD and parathyroid hormone (PTH) in children. To this end, this study was aimed at evaluating the lowest 25-OHD level that suppresses the production of parathyroid hormone in children. Methods A retrospective record review was performed for children aged 0.2 to 18 years (n=193; 106 boys and 87 girls) who underwent simultaneous measurements of serum 25-OHD and PTH levels between January 2010 and June 2014. Results The inflection point of serum 25-OHD level for maximal suppression of PTH was at 18.0 ng/mL (95% confidence interval, 14.3–21.7 ng/mL). The median PTH level of the children with 25-OHD levels of <18.0 ng/mL was higher than that of children with 25-OHD levels ≥ 18.0 ng/mL (P<0.0001). The median calcium level of children with 25-OHD levels<18.0 ng/mL was lower than that of children with 25-OHD levels≥18.0 ng/mL (P=0.0001). The frequency of hyperparathyroidism was higher in the children with 25-OHD levels<18.0 ng/mL than in the children with 25-OHD levels≥18.0 ng/mL (P<0.0001). Hypocalcemia was more prevalent in the children with 25-OHD levels<18.0 ng/mL than in the children with 25-OHD levels≥18.0 ng/mL (P<0.0001). Conclusion These data suggest that a vitamin D level of 18.0 ng/mL could be the criterion for 25-OHD deficiency in children at the inflection point of the maximal suppression of PTH. PMID:28289433

  9. Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism

    PubMed Central

    Meola, Mario; Petrucci, Ilaria; Barsotti, Giuliano

    2009-01-01

    Background. The effect of cinacalcet on the structural pattern of hyperplastic parathyroid glands was evaluated, using high-resolution colour Doppler (CD) sonography, in haemodialysis patients with severe, inadequately controlled, secondary hyperparathyroidism (sHPT). Methods. Nine patients (6 males, 3 females; mean age ± SD, 55.5 ± 12.6 years) received cinacalcet, with adaptation of existing concomitant therapies. Biochemical parameters and the morphology and vascular pattern of hyperplastic parathyroid glands were measured at baseline and every 6 months thereafter, for a follow-up period of 24–30 months. Results. At baseline, 28 hyperplastic glands were identified. Cinacalcet led to a reduction in glandular volume during the course of the study: 68% in glands with a baseline volume <500 mm3 and 54% in glands with a baseline volume ≥500 mm3. The mean volume ± SD of glands <500 mm3 changed significantly from the baseline (233 ± 115 mm3) to the end of follow-up (102 ± 132 mm3, P = 0.007). Levels of mean serum phosphorus, calcium and calcium–phosphorus product decreased, but not significantly, whereas there were significant decreases in mean parathyroid hormone ± SD levels (1196 ± 381 pg/ml versus 256 ± 160 pg/ml; P < 0.0001) and alkaline phosphatase ± SD levels (428 ± 294 versus 223 ± 88 IU/l; P = 0.04), accompanied by an improvement in a subjective clinical score. Conclusions. Cinacalcet, in combination with conventional treatments, led to an improvement in biochemical and clinical parameters of sHPT and reduced glandular volume in patients with severe sHPT. Volume reduction was more evident in smaller glands. Longer term, larger, randomized clinical trials are needed to confirm these preliminary findings and to further define a more systematic approach in the treatment of sHPT. PMID:19181759

  10. Trends in intraoperative neural monitoring for thyroid and parathyroid surgery amongst otolaryngologists and general surgeons.

    PubMed

    Ho, Yan; Carr, Michele M; Goldenberg, David

    2013-09-01

    The role of intraoperative neural monitoring (IONM) in thyroid and parathyroid surgery remains a controversial subject for surgeons regardless of surgical training and background. This study aims to compare usage patterns and motivations behind IONM among otolaryngologist-head and neck surgeons (OTO-HNS) and general surgeons (GS) performing thyroid and parathyroid surgery. The study is a multi-institution survey of 103 otolaryngology and affiliated 103 GS programs in the US. 206 surveys were sent to OTO-HNS and GS academic program directors with a response rate of 44.7 %. Of those who performed thyroid surgery, 80.6 % of OTO-HNS and 48.0 % of GS surgeons reported using IONM. 44.3 % of OTO-HNS and 30.8 % of GS respondents used IONM in all thyroid cases. For thyroid surgery, as surgical volume increased, surgeons were more likely to use IONM more frequently. Fourteen percent (14 %) of the OTO-HNS and 41.7 % of the GS respondents used IONM primarily to locate the RLN. Forty percent (40 %) of the OTO-HNS and 8.3 % of the GS used IONM for medicolegal reasons. The majority of OTO-HNS programs use IONM for thyroid and parathyroid surgery, whereas less than half of GS programs regularly use IONM for these surgeries. Thyroid surgeons, with larger thyroid surgery volume, regardless of discipline, tend to use IONM more. The motivations for using IONM differ significantly between OTO-HNS and general surgeons in that more GS use it for locating the RLN, and more OTO-HNS use it for continuous monitoring of the nerve during resection and for medicolegal purposes.

  11. Parathyroid hormone-related peptide in lactation and in umbilical cord blood.

    PubMed

    Khosla, S; Johansen, K L; Ory, S J; O'Brien, P C; Kao, P C

    1990-11-01

    Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Multiple endocrine neoplasia similar to human subtype 2A in a dog: Medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma

    PubMed Central

    Arias, E.A. Soler; Castillo, V.A.; Trigo, R.H.; Caneda Aristarain, M.E.

    2016-01-01

    Human multiple endocrine neoplasia subtype 2A (MEN 2A) is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma in the same individual. In this report, a case of a female Rottweiler with medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma was described. Clinical manifestations of muscle weakness, polydipsia, polyuria, diarrhea and weight loss were observed. Two adrenal neoplasms were identified incidentally by ultrasonography, and tumor in the left thyroid lobe was identified by palpation. Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid carcinoma. This case in a dog is presenting neoplastic characteristics similar to human MEN 2A and emphasizing the importance of using immunohistochemistry for confirmation. PMID:27822452

  13. The Associative Meaning and Content Validity of Selected Elements from the Industrial Arts Curriculum Project's Taxonomy as Determined by Continued Word Association.

    ERIC Educational Resources Information Center

    Mason, Emmett Elwell

    Industrial management concepts in the taxonomy of the Industrial Arts Curriculum Project (IACP) at The Ohio State University were the focus of this study. The purposes were: (1) to determine the associative meanings which were held by manufacturing management personnel for 14 selected management concepts, (2) to determine the principal…

  14. Generalized-ensemble simulations of the human parathyroid hormone fragment PTH(1-34)

    NASA Astrophysics Data System (ADS)

    Hansmann, Ulrich H. E.

    2004-01-01

    A generalized-ensemble technique, multicanonical sampling, is used to study the folding of a 34-residue human parathyroid hormone fragment. An all-atom model of the peptide is employed and the protein-solvent interactions are approximated by an implicit solvent. Our results demonstrate that generalized-ensemble simulations are well suited to sample low-energy structures of such large polypeptides. Configurations with a root-mean-square deviation to the crystal structure of less than 1 Å are found. Finally, we discuss limitations of our implicit solvent model.

  15. Normochromic normocytic anemia in a postmenopausal woman with severe osteoporosis treated with intermittent parathyroid hormone.

    PubMed

    Anastasilakis, Athanasios D; Savvides, Mattheos; Polyzos, Stergios A; Georgopoulos, Christos; Delaroudis, Sideris

    2010-01-01

    Intermittent exogenous parathyroid hormone (PTH) is a potent osteoanabolic agent used for the treatment of severe osteoporosis. Two molecules of recombinant PTH are commercially available: the full-length PTH (PTH 1-84) and teriparatide (PTH 1-34). We present the first report of PTH-induced mild, asymptomatic, normochromic normocytic anemia in a postmenopausal woman treated sequentially with PTH 1-84 and PTH 1-34. Anemia was more pronounced with PTH 1-84 compared to PTH 1-34 and was reversed with each regimen discontinuation. We suggest monitoring of hematocrit and hemoglobin in PTH-treated patients, especially when PTH 1-84 is used.

  16. [Surgical discovery of parathyroid glands and the recurrent laryngeal nerve. Application of well known embryological concepts in the operating room].

    PubMed

    Chevallier, J M; Martelli, H; Wind, P

    1995-01-01

    Surgery for thyroid or parathyroid glands has to be logical. It is based upon a precise knowledge of the development of the 3rd and 4th pharyngeal pouches and aortic arches. Pharyngeal pouches are endodermal derivatives of the lateral walls of the early foregut. Parathyroid glands have an ectodermal origin in concert with inductive forces of cells derived from the neural crest (which also creates parafollicular cells secreting calcitonin). From the third pouch thymus and parathyroid III move down together because of the cervical flexure and heart's "descent" (stages 14 to 20 mm). The fourth pouch gives rise to the so called "caudal pharyngeal complex" constituted by parathyroid IV dorsally, a "lateral thyroid" ventrally and an ultimo-branchial body derived from the fifth pouch. The thyroid gland first appears at the 4th week as a thickening of the endoderm of the floor of the pharynx which evaginates as a diverticulum in front of the trachea below. This medial component of the thyroid joins both lateral thyroids derived from the caudal pharyngeal complexes to form a bi-lobed structure with an isthmus. The lateral edge of the adult thyroid lobe has a thickening which is called Zuckerkandl's tuberculum because of the fusion of the ultimobranchial body into the principal médial thyroid process. This tuberculum lies in front of the caudal thyroid artery born from the 4th aortic arch. The recurrent laryngeal nerve courses round the 4th aortic arch: therefore parathyroids IV have to be above and behind the nerve and parathyroids III below and in front of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Identification and preservation of the parathyroid gland during total thyroidectomy in dogs with bilateral thyroid carcinoma: a report of six cases.

    PubMed

    Fukui, Sho; Endo, Yoshifumi; Hirayama, Kazuko; Taniyama, Hiroyuki; Kadosawa, Tsuyoshi

    2015-06-01

    Simultaneous removal of bilateral thyroid tumors was performed while preserving the parathyroid gland in six dogs. At least one external parathyroid gland was identified in all dogs. In five cases, the external parathyroid gland and its blood supply were preserved intact. In one dog, the vessels supplying the external parathyroid gland had been invaded by the tumor, and the gland was thus removed and reimplanted into the sternohyoid muscle. That dog required postoperative treatment with oral calcium gluconate and vitamin D3. Local tumor recurrence was not observed in any of the cases. The mean survival time was 920 days. We found that the external parathyroid gland could be identified and preserved in most dogs undergoing total thyroidectomy.

  18. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

    PubMed Central

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-01

    Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

  19. Lithology determination from well logs with fuzzy associative memory neural network

    SciTech Connect

    Chang, H.C.; Chen, H.C.; Fang, J.H.

    1997-05-01

    An artificial intelligence technique of fuzzy associative memory is used to determine rock types from well-log signatures. Fuzzy associative memory (FAM) is a hybrid of neutral network and fuzzy expert system. This new approach combines the learning ability of neural network and the strengths of fuzzy linguistic modeling to adaptively infer lithologies from well-log signatures based on (1) the relationships between the lithology and log signature that the neural network have learned during the training and/or (2) geologist`s knowledge about the rocks. The method is applied to a sequence of the Ordovician rock units in northern Kansas. This paper also compares the performances of two different methods, using the same data set for meaningful comparison. The advantages of FAM are (1) expert knowledge acquired by geologists is fully utilized; (2) this knowledge is augmented by the neural network learning from the data, when available; and (3) FAM is transparent in that the knowledge is explicitly stated in the fuzzy rules.

  20. An analytical scheme for determining forms of sulphur in oil shales and associated rocks

    USGS Publications Warehouse

    Tuttle, M.L.; Goldhaber, M.B.; Williamson, D.L.

    1986-01-01

    An analytical scheme for determining various forms of sulphur in oil shales and associated rocks is presented. Acid-soluble sulphate, sulphur contained in monosulphide and in disulphide minerals, and organically-bound sulphur are all quantitatively recovered as separate fractions. Finely-ground oil-shale samples are treated in an inert atmosphere with 6M hydrochloric acid to dissolve the acid-soluble sulphate minerals and form H2S from the decomposition of monosulphide minerals. The acid-soluble sulphate is precipitated as barium sulphate and the H2S is collected and weighed as silver sulphide. Disulphide minerals in the solid residue from the acid treatment are reduced by an acidified Cr(II) solution in an inert atmosphere, releasing the sulphide as H2S. The H2S is collected as silver sulphide. An Eschka fusion oxidizes and solubilizes all sulphur remaining within the Cr(II)-treated residue. This sulphate represents organically-bound sulphur and is collected as barium sulphate. The analytical procedures have been verified by using 57Fe Mo??ssbauer spectroscopy. Good agreement between the chemical and Mo??ssbauer data substantiated the sequential removal of the forms of sulphur and also demonstrated the ability of Mo??ssbauer spectroscopy to determine the absolute quantities of iron present in specific minerals. ?? 1986.

  1. Fragile X Mental Retardation protein determinants required for its association with polyribosomal mRNPs.

    PubMed

    Mazroui, Rachid; Huot, Marc-Etienne; Tremblay, Sandra; Boilard, Nathalie; Labelle, Yves; Khandjian, Edouard W

    2003-12-01

    Fragile X Mental Retardation protein (FMRP) is an RNA-binding protein that contains multiple domains with apparently differential affinity to mRNA and to the ribonucleotide homopolymer poly(G). Attempts have been made to map the RNA-binding sites along the protein sequence with a view to determining which of the KH1, KH2 and RGG domains are required to recognize and bind to RNA. While these studies have greatly contributed to the delineation of domains that bind homopolymers or mRNA in vitro, little is known concerning their implications in FMRP function(s) in vivo. To address this question, we have prepared a series of FMRP versions, in which each known in vitro functional domain has been individually deleted, leaving the rest of the protein intact. Constructs with deletions in the protein-protein interaction and RNA-binding as well as in the phosphorylation domains were expressed in STEK-KO cells lacking FMRP and their recruitment into polyribosomal mRNPs and their intra-cellular localization were determined. Our results indicate that the KH RNA-binding domains and the Protein-Protein Interacting domain are essential for FMRP to associate with polyribosomal mRNPs, while the RGG box and the phosphorylated domains are dispensable.

  2. An analytical scheme for determining forms of sulphur in oil shales and associated rocks.

    PubMed

    Tuttle, M L; Goldhaber, M B; Williamson, D L

    1986-12-01

    An analytical scheme for determining various forms of sulphur in oil shales and associated rocks is presented. Acid-soluble sulphate, sulphur contained in monosulphide and in disulphide minerals, and organically-bound sulphur are all quantitatively recovered as separate fractions. Finely-ground oil-shale samples are treated in an inert atmosphere with 6M hydrochloric acid to dissolve the acid-soluble sulphate minerals and form H(2)S from the decomposition of monosulphide minerals. The acid-soluble sulphate is precipitated as barium sulphate and the H(2)S is collected and weighed as silver sulphide. Disulphide minerals in the solid residue from the acid treatment are reduced by an acidified Cr(II) solution in an inert atmosphere, releasing the sulphide as H(2)S. The H(2)S is collected as silver sulphide. An Eschka fusion oxidizes and solubilizes all sulphur remaining within the Cr(II)-treated residue. This sulphate represents organically-bound sulphur and is collected as barium sulphate. The analytical procedures have been verified by using (57)Fe Mössbauer spectroscopy. Good agreement between the chemical and Mössbauer data substantiated the sequential removal of the forms of sulphur and also demonstrated the ability of Mössbauer spectroscopy to determine the absolute quantities of iron present in specific minerals.

  3. Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia.

    PubMed

    Oest, Megan E; Gong, Bo; Esmonde-White, Karen; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A; Morris, Michael D

    2016-05-01

    As part of our ongoing efforts to understand underlying mechanisms contributing to radiation-associated bone fragility and to identify possible treatments, we evaluated the longitudinal effects of parathyroid hormone (PTH) treatment on bone quality in a murine model of limited field irradiation. We hypothesized PTH would mitigate radiation-induced changes in the chemical composition and structure of bone, as measured by microscope-based Raman spectroscopy. We further hypothesized that collagen crosslinking would be especially responsive to PTH treatment. Raman spectroscopy was performed on retrieved tibiae (6-7/group/time point) to quantify metrics associated with bone quality, including: mineral-to-matrix ratio, carbonate-to-phosphate ratio, mineral crystallinity, collagen crosslink (trivalent:divalent) ratio, and the mineral and matrix depolarization ratios. Irradiation disrupted the molecular structure and orientation of bone collagen, as evidenced by a higher collagen crosslink ratio and lower matrix depolarization ratio (vs. non-irradiated control bones), persisting until 12weeks post-irradiation. Radiation transiently affected the mineral phase, as evidenced by increased mineral crystallinity and mineral-to-matrix ratio at 4weeks compared to controls. Radiation decreased bone mineral depolarization ratios through 12weeks, indicating increased mineral alignment. PTH treatment partially attenuated radiation-induced increases in collagen crosslink ratio, but did not restore collagen or mineral alignment. These post-radiation matrix changes are consistent with our previous studies of radiation damage to bone, and suggest that the initial radiation damage to bone matrix has extensive effects on the quality of tissue deposited thereafter. In addition to maintaining bone quality, preventing initial radiation damage to the bone matrix (i.e. crosslink ratio, matrix orientation) may be critical to preventing late-onset fragility fractures.

  4. Determinants of Bowel Preparation Quality and Its Association With Adenoma Detection: A Prospective Colonoscopy Study.

    PubMed

    Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Lam, Thomas Y T; Luk, Arthur K C; Tang, Raymond S Y; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2016-01-01

    The predictors of poor bowel preparation in colorectal cancer screening participants have not been adequately studied, and the association between the quality of bowel preparation and adenoma detection has not been firmly established. This study examined the determinants of poor bowel preparation, and evaluated its relationship with adenoma detection.We included subjects aged between 50 and 70 years who received colonoscopy between 2008 and 2014 in a colorectal cancer screening program in Hong Kong. The quality of the bowel preparation was assessed by colonoscopists, and the factors associated with poor bowel cleansing were evaluated by a binary logistic regression analysis. A multivariate regression model was constructed to evaluate if poor bowel preparation was associated with detection of colorectal neoplasia.From 5470 screening participants (average age 57.7 years, SD 4.9), 1891 (34.6%) had poor or fair bowel preparation. The average cecal intubation time was 7.0 minutes (SD 5.4; range 1.22-36.9 minutes) and the average colonoscopy withdrawal time was 10.8 minutes (SD 6.9; range 6.0-107.0 minutes). Among all, 26.5% had colorectal neoplasia and 5.5% had advanced neoplasia. Older age (≥60 years; adjusted odds ratio [AOR] = 1.19-1.38, P = 0.02-0.04), male sex (AOR = 1.38, 95% confidence interval [CI] 1.19-1.60, P < 0.001), and current smoking (AOR = 1.41, 95% CI 1.14-1.75, P = 0.002) were significantly associated with poor/fair bowel preparation. Poorer cleansing resulted in significantly lower detection rate of neoplasia (AOR = 0.35-0.62) and advanced neoplasia (AOR = 0.36-0.50) irrespective of polyp size.Steps to improve proper procedures of bowel preparation are warranted, especially among subjects at risk of poor bowel preparation. Strategies should be implemented to improve bowel cleansing, which is now demonstrated as a definite quality indicator.

  5. Differential regulation of the parathyroid hormone-related protein gene P1 and P3 promoters by cAMP.

    PubMed

    Chilco, P J; Leopold, V; Zajac, J D

    1998-03-16

    The role of calcitonin, and other agonists which activate the cAMP pathway, in regulating transcription of the human parathyroid hormone-related protein (PTHrP) gene was investigated in a human lung cancer cell line (BEN). Both calcitonin and forskolin caused a 5-6-fold increase in transcription initiated from both the P1 and P3 promoters, but with no observed effect on the P2 promoter. Maximal 6-fold activation of the P1 promoter occurred at 16 h post-stimulation and effects of calcitonin were observed within the pM range. The PKC agonist, phorbol 12-myristate 13-acetate diester (PMA), did not modulate transcription initiated from the P1 promoter. The ionophore ionomycin had a small effect on transcription of the P1 promoter, and transcriptional control may involve an interaction between the cAMP and intracellular calcium second messenger pathways. Deletion mapping studies indicated that increases in transcription of the human PTHrP gene is being mediated via a CRE element situated at -3313 to -3306 upstream of the P1 promoter. Mutational analysis of this CRE element confirmed a role for this sequence in mediating the increase in transcription effected by cAMP. Consistent with these transfection studies, RT-PCR of PTHrP mRNA also indicated a significant increase in transcripts generated from the P1 promoter. Gel retardation assays utilising a fragment of the P1 promoter region, encompassing the putative CRE, determined that nuclear proteins were binding to this region. Competition binding studies with labelled probe and cold competitors determined that the binding was specific for this sequence. A wild-type CRE consensus oligonucleotide also competed for binding with this sequence.

  6. Vitamin D Status and Its Association with Parathyroid Hormone Concentration in Brazilians

    PubMed Central

    Martins, Juliana Sálvio; Palhares, Magda de Oliveira; Teixeira, Octávio Cury Mayrink

    2017-01-01

    Vitamins are organic compounds that play a vital role in the control of metabolic processes. The D complex is considered a nutrient with a hormonal action and has an important participation in the constant maintenance of serum and extracellular calcium levels. The present study aims to analyze the results of 105.588 vitamin D (25(OH)D) measurements obtained from a database from a clinical analysis laboratory in Brazil, between the years of 2011 and 2013. The values of 25(OH)D were correlated with age, gender, and values of PTH. The results show a high prevalence of values of 25(OH)D considered inadequate, characterizing 76% of the studied population. It was observed that 26,5% of the individuals had deficiency and 49,5% had insufficiency of vitamin D. It was also shown that there was a negative correlation between 25(OH)D and PTH levels. In conclusion, this study is in accordance with others that show a high prevalence of vitamin D deficiency in different populations and alerts us for the importance of these measurements and analysis in clinical practice and as a base for diagnosis and treatment of hypovitaminosis. PMID:28265467

  7. Potential role of carbon nanoparticles in protection of parathyroid glands in patients with papillary thyroid cancer.

    PubMed

    Yu, Wenbin; Zhu, Lijun; Xu, Guohui; Song, Yuntao; Li, Guojun; Zhang, Naisong

    2016-10-01

    As a novel type of lymphatic tracer, carbon nanoparticles (CNs) were reported not to stain parathyroid glands (PGs) into black, so it may have a clinical potential in protection of PGs during thyroidectomy. The purpose of this study was to investigate the clinical application and significance of CN in protection of PGs from surrounding tissues.A total of 82 consecutive patients were enrolled into this study and were divided into CN group and control group. Parathyroid function (hypoparathyroidism and hypocalcemia) was evaluated.The identification rates of PGs (≤2) and PGs (≥3) were 24.4% and 75.6% in the CN group and 46.3% and 53.7% in the control group, respectively. The difference in the identification rates between the 2 groups was statistically significant (P = 0.038). Pathological results revealed 3 accidental PGs resection occurred in the CN group, whereas 9 accidental PGs removal occurred in the control group. The difference was statistically significant (P = 0.046). Moreover, the incidence of the patients with hypoparathyroidism was statistically significant between the 2 groups (36.6% in CN group vs 53.7% in control group, P = 0.043) at day 1, but not at day 7 (P = 0.424).CN may have a potential in protecting PGs clinically.

  8. Structure-Inherent Targeting of NIR Fluorophores for Parathyroid and Thyroid Gland Imaging

    PubMed Central

    Hyun, Hoon; Park, Min Ho; Owens, Eric A.; Wada, Hideyuki; Henary, Maged; Handgraaf, Hein J.M.; Vahrmeijer, Alexander L.; Frangioni, John V.; Choi, Hak Soo

    2014-01-01

    The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible create tissue-specific near-infrared fluorophores using the inherent chemical structure. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head/neck surgery, the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake in the specific glands after a single intravenous injection of only 0.06 mg kg−1 in a pig. Using a dual-channel near-infrared imaging system, we demonstrate the real-time, high-sensitivity, unambiguous identification of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays the foundation for head/neck surgery performed with increased precision and efficiency, and potentially lowers morbidity, and a general strategy for targeted near-infrared fluorophore development. PMID:25559343

  9. Successful cinacalcet treatment of refractory secondary hyperparathyroidism due to multiple lung parathyroid adenomas

    PubMed Central

    Sugi, Orie; Kimata, Naoki; Miwa, Naoko; Otsubo, Shigeru; Nitta, Kosaku; Akiba, Takashi

    2010-01-01

    We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain. PMID:25984040

  10. Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression

    NASA Technical Reports Server (NTRS)

    Partridge, N. C.; Bloch, S. R.; Pearman, A. T.

    1994-01-01

    Parathyroid hormone (PTH) plays a central role in regulation of calcium metabolism. For example, excessive or inappropriate production of PTH or the related hormone, parathyroid hormone related protein (PTHrP), accounts for the majority of the causes of hypercalcemia. Both hormones act through the same receptor on the osteoblast to elicit enhanced bone resorption by the osteoclast. Thus, the osteoblast mediates the effect of PTH in the resorption process. In this process, PTH causes a change in the function and phenotype of the osteoblast from a cell involved in bone formation to one directing the process of bone resorption. In response to PTH, the osteoblast decreases collagen, alkaline phosphatase, and osteopontin expression and increases production of osteocalcin, cytokines, and neutral proteases. Many of these changes have been shown to be due to effects on mRNA abundance through either transcriptional or post-transcriptional mechanisms. However, the signal transduction pathway for the hormone to cause these changes is not completely elucidated in any case. Binding of PTH and PTHrP to their common receptor has been shown to result in activation of protein kinases A and C and increases in intracellular calcium. The latter has not been implicated in any changes in mRNA of osteoblastic genes. On the other hand activation of PKA can mimic all the effects of PTH; protein kinase C may be involved in some responses. We will discuss possible mechanisms linking PKA and PKC activation to changes in gene expression, particularly at the nuclear level.

  11. Phase II Trial of Parathyroid Hormone following Double Umbilical Cord Blood Transplantation

    PubMed Central

    Ballen, Karen K; Mendizabal, Adam M; Cutler, Corey; Politikos, Ioannis; Jamieson, Katarzyna; Shpall, Elizabeth J; Dey, Bimalangshu R; Attar, Eyal; McAfee, Steven; Delaney, Colleen; McCarthy, Philip; Ball, Edward D; Kamble, Ram; Avigan, David; Maziarz, Richard T; Ho, Vincent T; Koreth, John; Alyea, Edwin; Soiffer, Robert; Wingard, John R; Boussiotis, Vicki; Spitzer, Thomas R; Antin, Joseph H

    2012-01-01

    Transplantation of one or two umbilical cord blood products is a useful alternative stem cell source. However, the limited number of stem cells in the infusion results in slow engraftment. In mouse models, administration of parathyroid hormone is an effective way to enhance the ability of limited numbers of hematopoietic stem cells to support hematopoiesis. In this study, patients received either a myeloablative or a reduced intensity double umbilical cord blood transplantation followed by parathyroid hormone at 100 μg daily for 28 days. Thirteen patients (median age 42 years) were enrolled. All patients engrafted; the median time to neutrophil and platelet engraftment >20x109 cells/L were 30 and 61 days respectively. The incidence of Grades II–IV acute GVHD was 38.5% at day 100. There were four deaths prior to Day 100, prompting early study closure. No patients receiving a myeloablative regimen relapsed. Overall survival at 6 months after transplantation was 62% and disease-free survival at 2 years was 39%. At the dose and schedule studied, there was no evidence that PTH influenced blood count recovery. PMID:22766223

  12. Comparison of imaging methods for diagnosing enlarged parathyroid glands in chronic renal failure

    SciTech Connect

    Takagi, H.; Tominaga, Y.; Uchida, K.; Yamada, N.; Kano, T.; Kawai, M.; Morimoto, T.

    1985-07-01

    Three noninvasive imaging methods, CT, scintigraphy with /sup 201/TlCl and /sup 99m/TcO4-, and ultrasonography, were performed on 36 patients with chronic renal failure and secondary hyperparathyroidism. The patients subsequently underwent total parathyroidectomy and parathyroid autograft. The detection rates of the three methods for the 143 excised parathyroid glands were compared according to gland weight and location. Computed tomography detected 53.8% of all glands and 77.6% of 76 glands weighing more than 500 mg. Scintigraphy detected 51.0% of all glands and 77.6% of glands heavier than 500 mg. Ultrasonography detected 42.7% of all glands and 65.8% of glands heavier than 500 mg. The detection rate of upper glands was best with CT (53.5 and 87.9%): that of lower glands was best with scintigraphy (62.0 and 78.6%). Although the combination of the three methods diagnosed 66.4% of all glands and 89.5% of glands heavier than 500 mg, CT and scintigraphy, the best two combinations, visualized 64.3 and 88.2%.

  13. Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

    PubMed Central

    Kumar, Amit; Baumann, Monika; Balbach, Jochen

    2016-01-01

    Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required. PMID:26932583

  14. Is intraoperative parathyroid hormone monitoring necessary in symptomatic primary hyperparathyroidism with concordant imaging?

    PubMed Central

    Nair, C. Gopalakrishnan; Babu, Misha J. C.; Jacob, Pradeep; Menon, Riju; Mathew, Jimmy

    2016-01-01

    Introduction: Symptomatic primary hyperparathyroidism (PHPT) is still seen frequently in referral centers all over India. These patients require parathyroidectomy and this study aimed to assess the roll of intraoperative parathyroid hormone (PTH) assay when concordant results of two localization studies were available. Study Design: We analyzed the case records of patients who underwent parathyroidectomy for PHPT from January 2005 to June 2015. Results: Of 143 patients included in the study, technetium 99m methoxyisobutylisonitrate dual phase scintigraphy showed true positive images in 93.7% and high definition ultrasonography in 84.6% of patients. Concordance in localization studies was observed in 121 (84.6%) patients, successful parathyroidectomy was done in 117 (96.7%) patients with concordant localization studies. Intraoperative PTH monitoring showed 97.84% sensitivity and 75% specificity and predicted failure in 2 patients with concordant imaging. However, re-exploration was not successful in these patients. Conclusion: When concordant result is available between parathyroid scintigraphy and anatomical imaging surgical cure rate is high in trained hands. Re-exploration is unlikely to be successful since these patients require higher imaging. PMID:27366718

  15. Parathyroid hormone-related protein is a factor in normal fish pituitary.

    PubMed

    Danks, J A; Devlin, A J; Ho, P M; Diefenbach-Jagger, H; Power, D M; Canario, A; Martin, T J; Ingleton, P M

    1993-11-01

    Using antibodies to the amino-terminal region of human parathyroid hormone-related protein (PTHrP) we have demonstrated PTHrP immunoreactivity in pituitaries and plasma of the sea bream (Sparus aurata). Pituitary cells at two distinct locations contained immunodetectable PTHrP; an anterior group in the rostral pars distalis which also contained immunoreactive thyroid stimulating hormone (TSH), and a posterior group lying at the border of the pars intermedia and proximal pars distalis between cells which stained with antibody to human corticotrophin-like intermediate lobe peptide. By Western blot analysis pituitary extracts contained two immunoreactive isoforms of PTHrP, one of 29 kDa and the other of 26 kDa. Media of pituitaries incubated for up to 14 days in Krebs-Ringer bicarbonate also had several isoforms of immunodetectable PTHrP, two of them corresponding to the 29- and 26-kDa molecular forms but there were in addition both larger and smaller molecules. The concentration of PTHrP in sea bream plasma was comparable with levels observed in human subjects with humoral hypercalcaemia of malignancy. There was no reaction between pituitary cells or pituitary extracts and antibody to human parathyroid hormone. Thus sea bream pituitary contains immunoreactive PTHrP, which appears to be released into medium during in vitro incubation and which may be a significant source of plasma immunoreactive PTHrP in vivo.

  16. Dimeric Arrangement of the Parathyroid Hormone Receptor and a Structural Mechanism for Ligand-induced Dissociation

    SciTech Connect

    Pioszak, Augen A.; Harikumar, Kaleeckal G.; Parker, Naomi R.; Miller, Laurence J.; Xu, H. Eric

    2010-06-25

    The parathyroid hormone receptor (PTH1R) is a class B G protein-coupled receptor that is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Little is known about the oligomeric state of the receptor and its regulation by hormone. The crystal structure of the ligand-free PTH1R extracellular domain (ECD) reveals an unexpected dimer in which the C-terminal segment of both ECD protomers forms an {alpha}-helix that mimics PTH/PTHrP by occupying the peptide binding groove of the opposing protomer. ECD-mediated oligomerization of intact PTH1R was confirmed in living cells by bioluminescence and fluorescence resonance energy transfer experiments. As predicted by the structure, PTH binding disrupted receptor oligomerization. A receptor rendered monomeric by mutations in the ECD retained wild-type PTH binding and cAMP signaling ability. Our results are consistent with the hypothesis that PTH1R forms constitutive dimers that are dissociated by ligand binding and that monomeric PTH1R is capable of activating G protein.

  17. High extracellular Ca2+ stimulates Ca2+-activated Cl- currents in frog parathyroid cells through the mediation of arachidonic acid cascade.

    PubMed

    Okada, Yukio; Imendra, Kotapola G; Miyazaki, Toshihiro; Hotokezaka, Hitoshi; Fujiyama, Rie; Toda, Kazuo

    2011-04-29

    Elevation of extracellular Ca(2+) concentration induces intracellular Ca(2+) signaling in parathyroid cells. The response is due to stimulation of the phospholipase C/Ca(2+) pathways, but the direct mechanism responsible for the rise of intracellular Ca(2+) concentration has remained elusive. Here, we describe the electrophysiological property associated with intracellular Ca(2+) signaling in frog parathyroid cells and show that Ca(2+)-activated Cl(-) channels are activated by intracellular Ca(2+) increase through an inositol 1,4,5-trisphophate (IP(3))-independent pathway. High extracellular Ca(2+) induced an outwardly-rectifying conductance in a dose-dependent manner (EC(50) ∼6 mM). The conductance was composed of an instantaneous time-independent component and a slowly activating time-dependent component and displayed a deactivating inward tail current. Extracellular Ca(2+)-induced and Ca(2+) dialysis-induced currents reversed at the equilibrium potential of Cl(-) and were inhibited by niflumic acid (a specific blocker of Ca(2+)-activated Cl(-) channel). Gramicidin-perforated whole-cell recording displayed the shift of the reversal potential in extracellular Ca(2+)-induced current, suggesting the change of intracellular Cl(-) concentration in a few minutes. Extracellular Ca(2+)-induced currents displayed a moderate dependency on guanosine triphosphate (GTP). All blockers for phospholipase C, diacylglycerol (DAG) lipase, monoacylglycerol (MAG) lipase and lipoxygenase inhibited extracellular Ca(2+)-induced current. IP(3) dialysis failed to induce conductance increase, but 2-arachidonoylglycerol (2-AG), arachidonic acid and 12S-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HPETE) dialysis increased the conductance identical to extracellular Ca(2+)-induced conductance. These results indicate that high extracellular Ca(2+) raises intracellular Ca(2+) concentration through the DAG lipase/lipoxygenase pathway, resulting in the activation of Cl(-) conductance.

  18. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism.

    PubMed

    Bowl, Michael R; Mirczuk, Samantha M; Grigorieva, Irina V; Piret, Sian E; Cranston, Treena; Southam, Lorraine; Allgrove, Jeremy; Bahl, Shailini; Brain, Caroline; Loughlin, John; Mughal, Zulf; Ryan, Fiona; Shaw, Nick; Thakker, Yogini V; Tiosano, Dov; Nesbit, M Andrew; Thakker, Rajesh V

    2010-05-15

    GCMB is a member of the small transcription factor family GCM (glial cells missing), which are important regulators of development, present in vertebrates and some invertebrates. In man, GCMB encodes a 506 amino acid parathyroid gland-specific protein, mutations of which have been reported to cause both autosomal dominant and autosomal recessive hypoparathyroidism. We ascertained 18 affected individuals from 12 families with autosomal recessive hypoparathyroidism and have investigated them for GCMB abnormalities. Four different homozygous germline mutations were identified in eight families that originate from the Indian Subcontinent. These consisted of a novel nonsense mutation R39X; a missense mutation, R47L in two families; a novel missense mutation, R110W; and a novel frameshifting deletion, I298fsX307 in four families. Haplotype analysis, using polymorphic microsatellites from chromosome 6p23-24, revealed that R47L and I298fsX307 mutations arose either as ancient founders, or recurrent de novo mutations. Functional studies including: subcellular localization studies, EMSAs and luciferase-reporter assays, were undertaken and these demonstrated that: the R39X mutant failed to localize to the nucleus; the R47L and R110W mutants both lost DNA-binding ability; and the I298fsX307 mutant had reduced transactivational ability. In order to gain further insights, we undertook 3D-modeling of the GCMB DNA-binding domain, which revealed that the R110 residue is likely important for the structural integrity of helix 2, which forms part of the GCMB/DNA binding interface. Thus, our results, which expand the spectrum of hypoparathyroidism-associated GCMB mutations, help elucidate the molecular mechanisms underlying DNA-binding and transactivation that are required for this parathyroid-specific transcription factor.

  19. Induction of Thermal and Mechanical Hypersensitivity by Parathyroid Hormone-related Peptide (PTHrP) Through Upregulation of TRPV1 Function and Trafficking

    PubMed Central

    Mickle, Aaron D.; Shepherd, Andrew J.; Loo, Lipin; Mohapatra, Durga P.

    2016-01-01

    The neurobiological mechanisms underlying chronic pain associated with cancers are not well understood. It has been hypothesized that factors specifically elevated in the tumor microenvironment sensitize adjacent nociceptive afferents. We show that parathyroid hormone-related peptide (PTHrP), which is found at elevated levels in the tumor microenvironment of advanced breast and prostate cancers, is a critical modulator of sensory neurons. Intraplantar injection of PTHrP led to the development of thermal and mechanical hypersensitivity in both male and female mice, which were absent in mice lacking functional transient receptor potential vanilloid-1 (TRPV1). The PTHrP treatment of cultured mouse sensory neurons enhanced action potential firing, and increased TRPV1 activation, which was dependent on protein kinase C (PKC) activity. Parathyroid hormone-related peptide induced robust potentiation of TRPV1 activation and enhancement of neuronal firing at mild acidic pH that is relevant to acidic tumor microenvironment. We also observed an increase in plasma membrane TRPV1 protein levels after exposure to PTHrP, leading to upregulation in the proportion of TRPV1-responsive neurons, which was dependent on the activity of PKC and Src kinases. Furthermore, co-injection of PKC or Src inhibitors attenuated PTHrP-induced thermal but not mechanical hypersensitivity. Altogether, our results suggest that PTHrP and mild acidic conditions could induce constitutive pathological activation of sensory neurons through upregulation of TRPV1 function and trafficking, which could serve as a mechanism for peripheral sensitization of nociceptive afferents in the tumor microenvironment. PMID:25970319

  20. Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability

    PubMed Central

    2010-01-01

    Introduction The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability. Methods The study includes 1,191 consecutive RA patients (85% women) and 1,019 controls, not on vitamin D supplements, from 22 Italian rheumatology centres. Together with parameters of disease activity, functional impairment, and mean sun exposure time, all patients had serum 25(OH)D measured in a centralized laboratory. Results A total of 55% of RA patients were not taking vitamin D supplements; the proportion of these with vitamin D deficiency (25(OH)D level <20 ng/ml) was 52%. This proportion was similar to that observed in control subjects (58.7%). One third of supplemented patients were still vitamin D deficient. In non-supplemented RA patients 25(OH)D levels were negatively correlated with the Health Assessment Questionnaire Disability Index, Disease Activity Score (DAS28), and Mobility Activities of daily living score. Significantly lower 25(OH)D values were found in patients not in disease remission or responding poorly to treatment, and with the highest Steinbrocker functional state. Body mass index (BMI) and sun exposure time were good predictors of 25(OH)D values (P < 0.001). The association between disease activity or functional scores and 25(OH)D levels remained statistically significant even after adjusting 25(OH)D levels for both BMI and sun exposure time. Conclusions In RA patients vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity and disability scores are inversely related to 25(OH)D levels. PMID:21114806

  1. A study on association of virulence determinants of verotoxic Escherichia coli isolated from cattle calves

    PubMed Central

    Parul, Singh; Bist, Basanti; Sharma, Barkha; Jain, Udit; Yadav, Janardan K.

    2016-01-01

    Aim: The present study was conducted to find the association among virulence determinants of verotoxic Escherichia coli (VTEC) isolated from cattle calf feces. Materials and Methods: A total of 216 cattle calf fecal samples were collected aseptically and processed under required conditions for the isolation of E. coli. The isolates were further subjected to multiplex polymerase chain reaction (mPCR) for the detection of virulent genes. All the VTEC isolates were serotyped at the Central Research Institute, Kasauli, Himachal Pradesh. The VTEC isolates were observed for the enterohemolysin production on washed sheep blood agar (wSBA). Results: A total of 177 presumptive E. coli were isolated from 216 calf fecal samples revealing an overall prevalence of E. coli to be 81.94%. A total of 32 (14.81%) isolates were detected as VTEC through mPCR. The prevalence of verotoxin genes vt1, vt2, and combination of vt1+vt2 in the VTEC isolates was found to be 12 (37.5%), 14 (43.75%), and 6 (18.75%), respectively. Other virulent genes eaeA and hlyA were found in 6 and 11 VTEC strains with prevalence values of 18.75% and 34.37%, respectively. A total of 13 different O serogroups were revealed in serotyping of 32 VTEC isolates. Out of 32 VTEC strains, only 26 (81.25%) were enterohemolytic on wSBA as they produced the characteristic small, turbid zone of hemolysis around the streaking line. Although enterohemolysin production has been attributed to the presence of hlyA gene, only 11 of 26 enterohemolysin producing VTEC were found to be harboring the hlyA gene (11/26) 42.03%. Conclusion: The present study concludes that there might be an association between the presence of verotoxin genes and enterohemolysin production in VTEC group of E. coli. PMID:27651684

  2. Critical determinants of mitochondria-associated neutral sphingomyelinase (MA-nSMase) for mitochondrial localization

    PubMed Central

    Rajagopalan, Vinodh; Canals, Daniel; Luberto, Chiara; Snider, Justin; Voelkel-Johnson, Christina; Obeid, Lina M.; Hannun, Yusuf A

    2014-01-01

    BACKGROUND A novel murine mitochondria-associated neutral sphingomyelinase (MA-nSMase) has been recently cloned and partially characterized. The subcellular localization of the enzyme was found to be predominantly in mitochondria. In this work, the determinants of mitochondrial localization and its topology were investigated. METHODS MA-nSMase mutants lacking consecutive regions and fusion proteins of GFP with truncated MA-nSMase regions were constructed and expressed in MCF-7 cells. Its localization was analyzed using confocal microscopy and sub-cellular fractionation methods. The sub-mitochondrial localization of MA-nSMase was determined using protease protection assay on isolated mitochondria. RESULTS The results initially showed that a putative mitochondrial localization signal (MLS), homologous to an MLS in the zebra-fish mitochondrial SMase is not necessary for the mitochondrial localization of the murine MA-nSMase. Evidence is provided to the presence of two regions in MA-nSMase that are sufficient for mitochondrial localization: a signal sequence (amino acids 24–6) that is responsible for the mitochondrial localization and an additional 'signal-anchor' sequence (amino acids 77–99) that anchors the protein to the mitochondrial membrane. This protein is topologically located in the outer mitochondrial membrane where both the C and N-termini remain exposed to the cytosol. CONCLUSIONS MA-nSMase is a membrane anchored protein with a MLS and a signal-anchor sequence at its N-terminal to localize it to the outer mitochondrial membrane. GENERAL SIGNIFICANCE Mitochondrial sphingolipids have been reported to play a critical role in cellular viability. This study opens a new window to investigate their cellular functions, and to define novel therapeutic targets. PMID:25484313

  3. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease

    PubMed Central

    Miyazaki, Márcia I.; Chiminacio Neto, Nelson; Padeski, Marcela C.; Barros, Ana Cláudia M.

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy. PMID:26745156

  4. Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV.

    PubMed

    Wang, P-Y; Currier, M A; Hansford, L; Kaplan, D; Chiocca, E A; Uchida, H; Goins, W F; Cohen, J B; Glorioso, J C; van Kuppevelt, T H; Mo, X; Cripe, T P

    2013-07-01

    Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. As PKR is a major cellular defense against Herpes simplex virus (HSV), and oncolytic HSV-1 (oHSV) mutants have shown promising antitumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was the most susceptible, NB122R was intermediate and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas downregulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a NB cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases, due to low virus receptor expression but also due to intact antiviral PKR signaling.

  5. Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease.

    PubMed

    Luz, Paola Rosa; Miyazaki, Márcia I; Chiminacio Neto, Nelson; Padeski, Marcela C; Barros, Ana Cláudia M; Boldt, Angelica B W; Messias-Reason, Iara J

    2016-01-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, whose sugar moieties are recognized by mannan binding lectin (MBL), a soluble pattern-recognition molecule that activates the lectin pathway of complement. MBL levels and protein activity are affected by polymorphisms in the MBL2 gene. We sequenced the MBL2 promoter and exon 1 in 196 chronic CD patients and 202 controls. The MBL2*C allele, which causes MBL deficiency, was associated with protection against CD (P = 0.007, OR = 0.32). Compared with controls, genotypes with this allele were completely absent in patients with the cardiac form of the disease (P = 0.003). Furthermore, cardiac patients with genotypes causing MBL deficiency presented less heart damage (P = 0.003, OR = 0.23), compared with cardiac patients having the XA haplotype causing low MBL levels, but fully capable of activating complement (P = 0.005, OR = 7.07). Among the patients, those with alleles causing MBL deficiency presented lower levels of cytokines and chemokines possibly implicated in symptom development (IL9, p = 0.013; PDGFB, p = 0.036 and RANTES, p = 0.031). These findings suggest a protective effect of genetically determined MBL deficiency against the development and progression of chronic CD cardiomyopathy.

  6. Inflammation and Cancer: Extra- and Intracellular Determinants of Tumor-Associated Macrophages as Tumor Promoters

    PubMed Central

    Vizler, Csaba; Kitajka, Klara; Puskas, Laszlo G.

    2017-01-01

    One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals. We discuss how these factors converge on intracellular determinants (STAT3, STAT6, STAT1, NF-κB, RORC1, and HIF-1α) of cell functions and drive the recruitment and polarization of TAMs. Since microRNAs (miRNAs) modulate macrophage polarization key miRNAs (miR-146a, miR-155, miR-125a, miR-511, and miR-223) are also discussed in the context of the inflammatory myeloid tumor compartment. Accumulating evidence suggests that high TAM infiltration correlates with disease progression and overall poor survival of cancer patients. Identification of molecular targets to develop new therapeutic interventions targeting these harmful tumor infiltrating myeloid cells is emerging nowadays. PMID:28197019

  7. Expression of HSV-1 Receptors in EBV-Associated Lymphoproliferative Disease Determines Susceptibility to Oncolytic HSV

    PubMed Central

    Wang, Pin-Yi; Currier, Mark A; Hansford, Loen; Kaplan, David; Chiocca, E. Antonio; Uchida, Hiroaki; Goins, William F.; Cohen, Justus B.; Glorioso, Joseph C.; van Kuppevelt, Toin H.; Mo, Xiaokui; Cripe, Timothy P

    2012-01-01

    Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disease (LPD) after hematopoietic stem cell or solid organ transplantation remains a life-threatening complication. Expression of the virus-encoded gene product, EBER, has been shown to prevent apoptosis via blockade of PKR activation. Because PKR is a major cellular defense against Herpes simplex virus, and oncolytic HSV-1 (oHSV) mutants have shown promising anti-tumor efficacy in preclinical models, we sought to determine whether EBV-LPD cells are susceptible to infection by oHSVs. We tested three primary EBV-infected lymphocyte cell cultures from neuroblastoma (NB) patients as models of naturally acquired EBV-LPD. NB12 was most susceptible, NB122R was intermediate, and NB88R2 was essentially resistant. Despite EBER expression, PKR was activated by oHSV infection. Susceptibility to oHSV correlated with the expression of the HSV receptor, nectin-1. The resistance of NB88R2 was reversed by exogenous nectin-1 expression, whereas down-regulation of nectin-1 on NB12 decreased viral entry. Xenografts derived from the EBV-LPDs exhibited only mild (NB12) or no (NB88R2) response to oHSV injection, compared with a neuroblastoma cell line that showed a significant response. We conclude that EBV-LPDs are relatively resistant to oHSV virotherapy, in some cases due to low virus receptor expression but also due to intact anti-viral PKR signaling. PMID:23254370

  8. Carotid hemodynamics is associated with monocyte count determined by serum homocysteine level in patients with essential hypertension.

    PubMed

    Jotoku, Masanori; Okura, Takafumi; Miyoshi, Ken-Ichi; Irita, Jun; Nagao, Tomoaki; Kukida, Masayoshi; Tanino, Akiko; Kudo, Kayo; Enomoto, Daijiro; Pei, Zouwei; Higaki, Jitsuo

    2015-01-01

    To examine the association between pulsatility index (PI) in the common carotid artery (CCA) as a marker of vascular resistance and cardiovascular risk factors, including serum homocysteine and inflammation, 67 hypertensive patients were enrolled. PI correlated with homocysteine and interleukin-6, monocyte count, gender, age and BMI, with monocyte count and age being independent determinants for PI. In turn, monocyte count correlated with homocysteine, tumor necrosis factor-alpha, and HDL-cholesterol, BMI, and gender, with HDL-cholesterol and homocysteine being independent determinants for monocyte count. These results indicated monocyte count determined by homocysteine is associated with arterial stiffness in hypertensive patients.

  9. Successful Localization of Abnormal Parathyroid Gland Using Ultrasound-Guided Methylene Blue Dye Injection in the Reoperative Neck.

    PubMed

    Haciyanli, Mehmet; Koruyucu, Melike Bedel; Erdoğan, Nezahat Karaca; Dere, Ozcan; Sarı, Erdem; Kumkumoğlu, Yusuf; Tavusbay, Cengiz; Kamer, Erdinc

    2015-12-01

    Persistent or recurrent hyperparathyroidism is a challenging problem for endocrine surgeons. The aim of this study was to review our experience using ultrasound-guided (US-G) methylene blue dye injection for the localization and removal of abnormal parathyroid glands in patients having primary hyperparathyroidism and previous neck surgery. Between January 2012 and May 2013, six consecutive patients with primary hyperparathyroidism (PHPT) and previous neck surgery underwent focused parathyroidectomy with the use of US-G methylene blue dye injections to localize the presumed parathyroid adenoma were included in the study. We analyzed the data of six patients who underwent reoperative parathyroid surgery using US-G methylene blue dye injection retrospectively. The dye injection was performed just prior to surgery. All patients were successfully treated for their hyperparathyroidism which was confirmed by at least 50 % drop in intraoperative parathormone level 10 min after resection. There were no complications related with US-G dye injection or with surgery. US-G methylene blue dye injection is a cheap, safe, and effective method for localization of diseased parathyroid glands and guiding surgery in the reoperative neck.

  10. Ultimobranchial body and parathyroid glands of the freshwater snake Natrix piscator in response to vitamin D3 administration.

    PubMed

    Srivastav, A K; Rani, L

    1992-06-01

    Vitamin D3 (20 I.U./100 g body wt) was administered to the freshwater snake Natrix piscator for 15 days. Elevation of serum calcium and inorganic phosphate levels was observed after the treatment. The ultimobranchial body became active whereas the parathyroid glands exhibited reduced activity.

  11. Parathyroid hormone, calcitonin, and vitamin D 1974: Present status of physiological studies and analysis of calcium homeostasis

    NASA Technical Reports Server (NTRS)

    Potts, J. T., Jr.; Swenson, K. G.

    1975-01-01

    The role of parathyroid hormone, calcitonin, and vitamin D in the control of calcium and bone metabolism was studied. Particular emphasis was placed on the physiological adaptation to weightlessness and, as a potential model for this purpose, on the immobilization characteristic of space flight or prolonged bed rest. The biosynthesis, control of secretion, and metabolism of these hormonal agents is considered.

  12. Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

    PubMed Central

    Kawakami, Kazuki; Takeshita, Ai; Furushima, Kenryo; Miyajima, Masayasu; Hatamura, Ikuji; Kuro-o, Makoto; Furuta, Yasuhide; Sakaguchi, Kazushige

    2017-01-01

    Secondary hyperparathyroidism, in which parathyroid hormone (PTH) is excessively secreted in response to factors such as hyperphosphataemia, hypocalcaemia, and low 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, is commonly observed in patients with chronic kidney disease (CKD), and is accompanied by high levels of fibroblast growth factor 23 (FGF23). However, the effect of FGF23 on the parathyroid glands (PG) remains controversial. To bind to FGF receptors, FGF23 requires αKlotho, which is highly expressed in the PG. Here, we examined the effects of Fgfr1–3, αKlotho, or Fgfr1–4 ablation specifically in the PG (conditional knockout, cKO). When mice with early to mid-stage CKD with and without cKO were compared, plasma concentrations of calcium, phosphate, FGF23, and 1,25(OH)2D did not change significantly. In contrast, plasma PTH levels, which were elevated in CKD mice, were significantly decreased in cKO mice. PG from CKD mice showed augmentation of cell proliferation, which was significantly suppressed by cKO. Parathyroid tissue cultured for 4 days showed upregulation of PTH secretion and cell proliferation in response to FGF23. Both these effects were inhibited by cKO. These findings suggest that FGF23 is a long-term inducer of parathyroid cell proliferation and PTH secretion, and is one cause of secondary hyperparathyroidism in CKD. PMID:28094278

  13. Rapid Decrease of Intact Parathyroid Hormone Could Be a Predictor of Better Response to Cinacalcet in Hemodialysis Patients

    PubMed Central

    Kim, Jwa-Kyung; Kwon, Young Joo; Kim, Soo Wan; Kim, Yeong-Hoon; Park, Cheol Whee; Choi, Kyu Bok; Hwang, Seung Duk

    2013-01-01

    Purpose Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response. Materials and Methods A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month. Results Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target. Conclusion Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH. PMID:23364981

  14. Parathyroid hormone inhibits TGF-β/Smad signaling and extracellular matrix proteins upregulation in rat mesangial cells.

    PubMed

    Peng, Fang-Fang; Xiao, Ze-Ling; Chen, Hong-Min; Chen, Yan; Zhou, Jian; Yu, Hong; Zhang, Bai-Fang

    2016-09-23

    Accumulation of glomerular matrix is a hallmark of diabetic nephropathy. TGF-β1 is a major cytokine mediating the production of various extracellular matrix (ECM) proteins. The aim of this study is to elucidate the effect of parathyroid hormone (PTH) on TGF-β1 and high glucose-induced upregulation of ECM proteins in primary mesangial cells from Sprague-Dawley rat. The results showed that PTH pretreatment prevented TGF-β1 and high glucose-induced Smad2/3 phosphorylation and consequent upregulation of fibronectin and type IV collagen within 4 h. The inhibitory effect of PTH is due to PTH1R activation, because knocking down PTH 1 receptor (PTH1R) by RNA interference reversed the inhibitory effect of PTH on TGF-β1 and high glucose-induced Smad2/3 phosphorylation and ECM upregulation. Furthermore, it is found that PTH1R associated with TGF-β type II receptor (TβR II) and both receptors internalized into the cytoplasm when mesangial cells were stimulated with PTH alone. The internalization of TβR II might reduce the amount of membrane TβR II, attenuate the sensitivity of mesangial cells to TGF-β1, and therefore inhibit Smad activation and ECM upregulation induced by TGF-β1 and high glucose. Further studies are needed to know whether the endocytic receptors are to be degraded or recycled, and evaluate the role of PTH in TGF-β1 signaling more comprehensively.

  15. Parathyroid hormone variability parameters for identifying high turnover osteodystrophy disease in hemodialysis patients: an observational retrospective cohort study.

    PubMed

    De Paola, Luciano; Coppolino, Giuseppe; Bolignano, Davide; Buemi, Michele; Lombardi, Luigi

    2010-12-01

    Abnormalities in bone morphology that develop secondary to chronic kidney disease are defined as renal osteodystrophy and are identified by bone biopsy. As systematic and sequential bone biopsy is not practicable on a large number of patients, various chemical bone markers are commonly used to detect the bone remodeling status in chronic kidney disease and to grade bone disease in the clinical setting. Recent literature has considered the effect of absolute levels of parathyroid hormone (PTH) on clinical outcomes and not the measurement of their change over time, the PTH variability. In a retrospective observational study, we examined PTH variability parameters in a group of hemodialysis patients as independent risk factors for high vs. low turnover osteopathy, and investigated their usefulness with respect to commonly used markers of renal osteodystrophy. The study was conducted on 90 chronic hemodialysis patients undergoing regular treatment at the same dialysis centre (Catanzaro, Italy) with standard bicarbonate dialysis. Patients were classified into either high or medium-low turnover osteopathy for the diagnosis based on renal osteodystrophy using the following criteria: PTH ≥ 400 pg/mL associated with bone ALP ≥ 20 ng/mL. We used a regression-based measurement of PTH variability, which was characterized by different parameters: PTH-Res-SD, PTH-Slope, PTH-Intercept, PTH-Abs-Var, and PTH-Res-SD. In our analysis, these parameters of PTH variability were demonstrated to be good independent predictive factors for high turnover osteodystrophy, and they had a greater sensitivity than the use of a single and/or mean PTH measurements in renal osteodystrophy classification.

  16. Parathyroid hormone-related protein (PTHrP) modulates adhesion, migration and invasion in bone tumor cells.

    PubMed

    Mak, Isabella W Y; Turcotte, Robert E; Ghert, Michelle

    2013-07-01

    Parathyroid-hormone-related protein (PTHrP) has been shown to be an important factor in osteolysis in the setting of metastatic carcinoma to the bone. However, PTHrP may also be central in the setting of primary bone tumors. Giant cell tumor of bone (GCT) is an aggressive osteolytic bone tumor characterized by osteoclast-like giant cells that are recruited by osteoblast-like stromal cells. The stromal cells of GCT are well established as the only neoplastic element of the tumor, and we have previously shown that PTHrP is highly expressed by these cells both in vitro and in vivo. We have also found that the stromal cells exposed to a monoclonal antibody to PTHrP exhibited rapid plate detachment and quickly died in vitro. Therefore, PTHrP may serve in an autocrine manner to increase cell proliferation and promote invasive properties in GCT. The purpose of this study was to use transcriptomic microarrays and functional assays to examine the effects of PTHrP neutralization on cell adhesion, migration and invasion. Microarray and proteomics data identified genes that were differentially expressed in GCT stromal cells under various PTHrP treatment conditions. Treatment of GCT stromal cells with anti-PTHrP antibodies showed a change in the expression of 13 genes from the integrin family relative to the IgG control. Neutralization of PTHrP reduced cell migration and invasion as evidenced by functional assays. Adhesion and anoikis assays demonstrated that although PTHrP neutralization inhibits cell adhesion properties, cell detachment related to PTHrP neutralization did not result in associated cell death, as expected in mesenchymal stromal cells. Based on the data presented herein, we conclude that PTHrP excreted by GCT stromal cells increases bone tumor cell local invasiveness and migration.

  17. Defective postnatal endochondral bone development by chondrocyte-specific targeted expression of parathyroid hormone type 2 receptor.

    PubMed

    Panda, Dibyendu Kumar; Goltzman, David; Karaplis, Andrew C

    2012-12-15

    The human parathyroid hormone type 2 receptor (PTH2R) is activated by PTH and by tuberoinfundibular peptide of 39 residues (TIP39), the latter likely acting as its natural ligand. Although the receptor is expressed at highest levels in the nervous system, we have observed that both PTH2R and TIP39 are expressed in the newborn mouse growth plate, with the receptor localizing in the resting zone and the ligand TIP39 localizing exclusively in prehypertrophic and hypertrophic chondrocytes. To address the role of PTH2R in postnatal skeletal growth and development, Col2a1-hPTH2R (PTH2R-Tg) transgenic mice were generated. The mice were viable and of nearly normal size at birth. Expression of the transgene in the growth plate was limited to chondrocytes. We found that chondrocyte proliferation was decreased, as determined by in vivo BrdU labeling of proliferating chondrocytes and CDK4 and p21 expression in the growth plate of Col2a1-hPTH2R transgenic mice. Similarly, the differentiation and maturation of chondrocytes was delayed, as characterized by decreased Sox9 expression and weaker immunostaining for the chondrocyte differentiation markers collagen type II and type X and proteoglycans. As well, there was altered expression of Gdf5, Wdr5, and β-catenin, factors implicated in chondrocyte maturation, proliferation, and differentiation.These effects impacted on the process of endochondral ossification, resulting in delayed formation of the secondary ossification center, and diminished trabecular bone volume. The findings substantiate a role for PTH2R signaling in postnatal growth plate development and subsequent bone mass acquisition.

  18. Preparation and in vivo evaluation of an orally available enteric-microencapsulated parathyroid hormone (1-34)-deoxycholic acid nanocomplex

    PubMed Central

    Hwang, Seung Rim; Seo, Dong-Hyun; Byun, Youngro; Park, Jin Woo

    2016-01-01

    The N-terminal 34-amino-acid peptide fragment of human parathyroid hormone PTH (1-34), is used clinically to treat osteoporosis; however, it is currently administered by a once-daily subcutaneous injection, resulting in poor patient compliance. We have developed enteric microcapsules containing an ionic nanocomplex between PTH (1-34) and lysine-linked deoxycholic acid (LysDOCA) for the oral delivery of PTH (1-34). We measured the particle size of the PTH/LysDOCA complex and assessed its biological activity by determining the cAMP content in MC3T3-E1 cells. We also assessed its permeability across a Caco-2 cell monolayer and the bioavailability of the intrajejunally administered PTH/LysDOCA complex compared with PTH (1-34) in rats. In addition, the antiosteoporotic activity of the PTH/LysDOCA complex, encapsulated in an enteric carrier by coaxial ultrasonic atomization, was evaluated after it was orally administered to ovariectomized (OVX) rats. The formation of an ionic complex between PTH (1-34) and LysDOCA produced nanoparticles of diameter 33.0±3.36 nm, and the bioactivity of the complex was comparable with that of PTH (1-34). The Caco-2 cell permeability and AUClast value of the PTH/LysDOCA (1:10) nanocomplex increased by 2.87- and 16.3-fold, respectively, compared with PTH (1-34) alone. Furthermore, the OVX rats treated with oral PTH/LysDOCA-loaded enteric microcapsules showed an increase in bone mineral density (159%), bone volume fraction (175%), and trabecular number (174%) compared with those in the OVX control group. Therefore, the PTH/LysDOCA nanocomplex oral delivery system is a promising treatment modality for osteoporosis because it improves osteogenesis and trabecular connectivity. PMID:27621618

  19. Preparation and in vivo evaluation of an orally available enteric-microencapsulated parathyroid hormone (1-34)-deoxycholic acid nanocomplex.

    PubMed

    Hwang, Seung Rim; Seo, Dong-Hyun; Byun, Youngro; Park, Jin Woo

    The N-terminal 34-amino-acid peptide fragment of human parathyroid hormone PTH (1-34), is used clinically to treat osteoporosis; however, it is currently administered by a once-daily subcutaneous injection, resulting in poor patient compliance. We have developed enteric microcapsules containing an ionic nanocomplex between PTH (1-34) and lysine-linked deoxycholic acid (LysDOCA) for the oral delivery of PTH (1-34). We measured the particle size of the PTH/LysDOCA complex and assessed its biological activity by determining the cAMP content in MC3T3-E1 cells. We also assessed its permeability across a Caco-2 cell monolayer and the bioavailability of the intrajejunally administered PTH/LysDOCA complex compared with PTH (1-34) in rats. In addition, the antiosteoporotic activity of the PTH/LysDOCA complex, encapsulated in an enteric carrier by coaxial ultrasonic atomization, was evaluated after it was orally administered to ovariectomized (OVX) rats. The formation of an ionic complex between PTH (1-34) and LysDOCA produced nanoparticles of diameter 33.0±3.36 nm, and the bioactivity of the complex was comparable with that of PTH (1-34). The Caco-2 cell permeability and AUClast value of the PTH/LysDOCA (1:10) nanocomplex increased by 2.87- and 16.3-fold, respectively, compared with PTH (1-34) alone. Furthermore, the OVX rats treated with oral PTH/LysDOCA-loaded enteric microcapsules showed an increase in bone mineral density (159%), bone volume fraction (175%), and trabecular number (174%) compared with those in the OVX control group. Therefore, the PTH/LysDOCA nanocomplex oral delivery system is a promising treatment modality for osteoporosis because it improves osteogenesis and trabecular connectivity.

  20. Parathyroid hormone/parathyroid hormone-related protein receptor signaling is required for maintenance of the growth plate in postnatal life

    PubMed Central

    Hirai, Takao; Chagin, Andrei S.; Kobayashi, Tatsuya; Mackem, Susan; Kronenberg, Henry M.

    2011-01-01

    Parathyroid hormone (PTH)-related protein (PTHrP), regulated by Indian hedgehog and acting through the PTH/PTHrP receptor (PPR), is crucial for normal cartilage development. These observations suggest a possible role of PPR signaling in the postnatal growth plate; however, the role of PPR signaling in postnatal chondrocytes is unknown. In this study, we have generated tamoxifen-inducible and cartilage-specific PPR KO mice to evaluate the physiological role of PPR signaling in postnatal chondrocytes. We found that inactivation of the PPR in chondrocytes postnatally leads to accelerated differentiation of chondrocytes, followed by disappearance of the growth plate. We also observed an increase of TUNEL-positive cells and activities of caspase-3 and caspase-9 in the growth plate, along with a decrease in phosphorylation of Bad at Ser155 in postnatal PPR KO mice. Administration of a low-phosphate diet, which prevents apoptosis of chondrocytes, prevented the disappearance of the growth plate. Taken together, these observations suggest that the major consequences of PPR activation are similar in both the fetal and postnatal growth plates. Moreover, chondrocyte apoptosis through the activation of a mitochondrial pathway may be involved in the process of premature disappearance of the growth plate by postnatal inactivation of the PPR in chondrocytes. PMID:21173257

  1. Parathyroid hormone/parathyroid hormone-related protein receptor signaling is required for maintenance of the growth plate in postnatal life.

    PubMed

    Hirai, Takao; Chagin, Andrei S; Kobayashi, Tatsuya; Mackem, Susan; Kronenberg, Henry M

    2011-01-04

    Parathyroid hormone (PTH)-related protein (PTHrP), regulated by Indian hedgehog and acting through the PTH/PTHrP receptor (PPR), is crucial for normal cartilage development. These observations suggest a possible role of PPR signaling in the postnatal growth plate; however, the role of PPR signaling in postnatal chondrocytes is unknown. In this study, we have generated tamoxifen-inducible and cartilage-specific PPR KO mice to evaluate the physiological role of PPR signaling in postnatal chondrocytes. We found that inactivation of the PPR in chondrocytes postnatally leads to accelerated differentiation of chondrocytes, followed by disappearance of the growth plate. We also observed an increase of TUNEL-positive cells and activities of caspase-3 and caspase-9 in the growth plate, along with a decrease in phosphorylation of Bad at Ser155 in postnatal PPR KO mice. Administration of a low-phosphate diet, which prevents apoptosis of chondrocytes, prevented the disappearance of the growth plate. Taken together, these observations suggest that the major consequences of PPR activation are similar in both the fetal and postnatal growth plates. Moreover, chondrocyte apoptosis through the activation of a mitochondrial pathway may be involved in the process of premature disappearance of the growth plate by postnatal inactivation of the PPR in chondrocytes.

  2. Parathyroid Disorders

    MedlinePlus

    ... make too much or too little hormone, it disrupts this balance. If they secrete extra PTH, you ... much phosphorous. Causes include injury to the glands, endocrine disorders, or genetic conditions. Treatment is aimed at ...

  3. Endocrine tumors associated with the vagus nerve.

    PubMed

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-09-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors.

  4. Endocrine tumors associated with the vagusnerve

    PubMed Central

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-01-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural-crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aorto-pulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors. PMID:27406876

  5. Metastasis of renal cell carcinoma to the parathyroid gland 16 years after radical nephrectomy: A case report

    PubMed Central

    Torregrossa, Liborio; Rotondo, Maria Isabella; Insilla, Andrea Cacciato; Galleri, David; Guidoccio, Federica; Miccoli, Paolo; Livolsi, Virginia A.; Basolo, Fulvio

    2016-01-01

    Renal cell carcinoma (RCC) has a high metastatic potential, and most commonly metastasizes via the bloodstream, although lymphatic metastases also occur. RCC is well-known for its propensity to metastasize to unusual sites, and late metastasis, even after a number of years, is common. The occurrence of RCC metastasis to the head and neck region is uncommon, and occurs primarily in the thyroid gland and in patients with widespread dissemination. Involvement of the parathyroid gland in metastatic carcinoma is extremely rare. In the present report, a case of metastasis confined to the parathyroid gland is described, likely with intrathyroidal localization, arising from a RCC that occurred 16 years after nephrectomy. A 66-year-old man was referred to the Department of Surgery of the University Hospital of Pisa (Pisa, Italy) with a preoperative fine-needle aspiration diagnosis of a follicular lesion in the context of nodular goiter of the thyroid gland. The previous medical history of the patient included a right nephrectomy for the treatment of clear cell RCC in February 1997. No other distant metastases were identified as of the latest follow-up in March 2014. At the time of thyroid surgery, the thyroid and parathyroid function tests were normal. The gross appearance of the surgical specimen was a multinodular goiter with a solid nodule measuring 33 mm on the left lobe of the thyroid gland. Microscopic examination revealed a completely encapsulated lesion consisting of clear cells arranged in a solid pattern and intermixed with fragments of parathyroid tissue. Following immunohistochemical examination, the clear cell lesion was negative for thyroid transcription factor-1 and thyroglobulin and strongly positive for epithelial membrane antigen, cluster of differentiation 10 and vimentin. To the best of our knowledge, this is the second case of metastasis to the parathyroid gland from a RCC reported in the literature. PMID:27899986

  6. Faecal Microbiota Composition in Adults Is Associated with the FUT2 Gene Determining the Secretor Status

    PubMed Central

    Wacklin, Pirjo; Tuimala, Jarno; Nikkilä, Janne; Sebastian Tims; Mäkivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Mättö, Jaana

    2014-01-01

    The human intestine is colonised with highly diverse and individually defined microbiota, which likely has an impact on the host well-being. Drivers of the individual variation in the microbiota compositions are multifactorial and include environmental, host and dietary factors. We studied the impact of the host secretor status, encoded by fucosyltransferase 2 (FUT2) -gene, on the intestinal microbiota composition. Secretor status determines the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucosa. The study population was comprised of 14 non-secretor (FUT2 rs601338 genotype AA) and 57 secretor (genotypes GG and AG) adult individuals of western European descent. Intestinal microbiota was analyzed by PCR-DGGE and for a subset of 12 non-secretor subjects and 12 secretor subjects additionally by the 16S rRNA gene pyrosequencing and the HITChip phylogenetic microarray analysis. All three methods showed distinct clustering of the intestinal microbiota and significant differences in abundances of several taxa representing dominant microbiota between the non-secretors and the secretors as well as between the FUT2 genotypes. In addition, the non-secretors had lower species richness than the secretors. The soft clustering of microbiota into enterotypes (ET) 1 and 3 showed that the non-secretors had a higher probability of belonging to ET1 and the secretors to ET3. Our study shows that secretor status and FUT2 polymorphism are associated with the composition of human intestinal microbiota, and appears thus to be one of the key drivers affecting the individual variation of human intestinal microbiota. PMID:24733310

  7. Sources and magnitude of bias associated with determination of polychlorinated biphenyls in environmental samples

    USGS Publications Warehouse

    Eganhouse, R.P.; Gossett, R.W.

    1991-01-01

    Recently complled data on the composition of commercial Aroclor mixtures and ECD (electron capture detector) response factors for all 209 PCB congeners are used to develop estimates of the bias associated with determination of polychlorinated blphenyis. During quantitation of multlcomponent peaks by congener-specific procedures error is introduced because of variable ECD response to isomeric PCBs. Under worst case conditions, the magnitude of this bias can range from less than 2% to as much as 600%. Multicomponent peaks containing the more highly and the lower chlorinated congeners experience the most bias. For this reason, quantitation of ??PCB in Aroclor mixtures dominated by these species (e.g. 1016) are potentially subject to the greatest error. Comparison of response factor data for ECDs from two laboratories shows that the sign and magnitude of calibration bias for a given multicomponent peak is variable and depends, in part, on the response characteristics of individual detectors. By using the most abundant congener (of each multicomponent peak) for purposes of calibration, one can reduce the maximum bias to less than 55%. Moreover, due to cancellation of errors, the bias resulting from summation of all peak concentrations (i.e. ??PCB) becomes vanishingly small (200%) and highly variable in sign and magnitude. In this case, bias originates not only from the incomplete chromatographic resolution of PCB congeners but also the overlapping patterns of the Aroclor mixtures. Together these results illustrate the advantages of the congener-specific method of PCB quantitation over the traditional Aroclor Method and the extreme difficulty of estimating bias incurred by the latter procedure on a post hoc basis.

  8. Resistance determinants and their association with different transposons in the antibiotic-resistant Streptococcus pneumoniae.

    PubMed

    Korona-Glowniak, Izabela; Siwiec, Radoslaw; Malm, Anna

    2015-01-01

    Multiple resistance of Streptococcus pneumoniae is generally associated with their unique recombination-mediated genetic plasticity and possessing the mobile genetic elements. The aim of our study was to detect antibiotic resistance determinants and conjugative transposons in 138 antibiotic-resistant pneumococcal strains isolated from nasopharynx of healthy young children from Lublin, Poland. These strains resistant to tetracycline and/or to chloramphenicol/erythromycin/clindamycin were tested by PCR using the specific genes as markers. The presence of Tn916 family transposons, carrying tet(M) and int/xisTn916, was observed in all of the tested strains. Tn916 was detected in 16 strains resistant only to tetracycline. Tn6002 and Tn3872-related element were found among 99 erm(B)-carrying strains (83.8% and 3.0%, resp.). Eight strains harbouring mef(E) and erm(B) genes were detected, suggesting the presence of Tn2010 and Tn2017 transposons. Among 101 chloramphenicol-resistant strains, two variants of Tn5252-related transposon were distinguished depending on the presence of int/xis5252 genes specific for cat gene-containing Tn5252 (75.2% of strains) or int Sp23FST81 gene, specific for cat-containing ICESp23FST81 element (24.8% of strains). In 6 strains Tn916-like and Tn5252-like elements formed a Tn5253-like structure. Besides clonal dissemination of resistant strains of pneumococci in the population, horizontal transfer of conjugative transposons is an important factor of the high prevalence of antibiotic resistance.

  9. Cropping systems and cultural practices determine the Rhizoctonia anastomosis groups associated with Brassica spp. in Vietnam.

    PubMed

    Hua, Gia Khuong Hoang; Bertier, Lien; Soltaninejad, Saman; Höfte, Monica

    2014-01-01

    Ninety seven Rhizoctonia isolates were collected from different Brassica species with typical Rhizoctonia symptoms in different provinces of Vietnam. The isolates were identified using staining of nuclei and sequencing of the rDNA-ITS barcoding gene. The majority of the isolates were multinucleate R. solani and four isolates were binucleate Rhizoctonia belonging to anastomosis groups (AGs) AG-A and a new subgroup of A-F that we introduce here as AG-Fc on the basis of differences in rDNA-ITS sequence. The most prevalent multinucleate AG was AG 1-IA (45.4% of isolates), followed by AG 1-ID (17.5%), AG 1-IB (13.4%), AG 4-HGI (12.4%), AG 2-2 (5.2%), AG 7 (1.0%) and an unknown AG related to AG 1-IA and AG 1-IE that we introduce here as AG 1-IG (1.0%) on the basis of differences in rDNA-ITS sequence. AG 1-IA and AG 1-ID have not been reported before on Brassica spp. Pathogenicity tests revealed that isolates from all AGs, except AG-A, induced symptoms on detached leaves of several cabbage species. In in vitro tests on white cabbage and Chinese cabbage, both hosts were severely infected by AG 1-IB, AG 2-2, AG 4-HGI, AG 1-IG and AG-Fc isolates, while under greenhouse conditions, only AG 4-HGI, AG 2-2 and AG-Fc isolates could cause severe disease symptoms. The occurrence of the different AGs seems to be correlated with the cropping systems and cultural practices in different sampling areas suggesting that agricultural practices determine the AGs associated with Brassica plants in Vietnam.

  10. Cropping Systems and Cultural Practices Determine the Rhizoctonia Anastomosis Groups Associated with Brassica spp. in Vietnam

    PubMed Central

    Soltaninejad, Saman; Höfte, Monica

    2014-01-01

    Ninety seven Rhizoctonia isolates were collected from different Brassica species with typical Rhizoctonia symptoms in different provinces of Vietnam. The isolates were identified using staining of nuclei and sequencing of the rDNA-ITS barcoding gene. The majority of the isolates were multinucleate R. solani and four isolates were binucleate Rhizoctonia belonging to anastomosis groups (AGs) AG-A and a new subgroup of A-F that we introduce here as AG-Fc on the basis of differences in rDNA-ITS sequence. The most prevalent multinucleate AG was AG 1-IA (45.4% of isolates), followed by AG 1-ID (17.5%), AG 1-IB (13.4%), AG 4-HGI (12.4%), AG 2-2 (5.2%), AG 7 (1.0%) and an unknown AG related to AG 1-IA and AG 1-IE that we introduce here as AG 1-IG (1.0%) on the basis of differences in rDNA-ITS sequence. AG 1-IA and AG 1-ID have not been reported before on Brassica spp. Pathogenicity tests revealed that isolates from all AGs, except AG-A, induced symptoms on detached leaves of several cabbage species. In in vitro tests on white cabbage and Chinese cabbage, both hosts were severely infected by AG 1-IB, AG 2-2, AG 4-HGI, AG 1-IG and AG-Fc isolates, while under greenhouse conditions, only AG 4-HGI, AG 2-2 and AG-Fc isolates could cause severe disease symptoms. The occurrence of the different AGs seems to be correlated with the cropping systems and cultural practices in different sampling areas suggesting that agricultural practices determine the AGs associated with Brassica plants in Vietnam. PMID:25372406

  11. Root-Associated Methane Oxidation and Methanogenesis: Key Determinants of Wetland Methane Emissions

    NASA Technical Reports Server (NTRS)

    King, G. M.

    1997-01-01

    During the award period, we have assessed the extent and controls of methane oxidation in north temperate wetlands. It is evident that wetlands have been a major global source of atmospheric methane in the past, and are so at present. It is also evident that microbial methane oxidation consumes a variable fraction of total wetland methane production, perhaps 10%-90%. Methane oxidation is thus a potentially important control of wetland methane emission. Our efforts have been designed to determine the extent of the process, its controls, and possible relationships to changes that might be expected in wetlands as a consequence of anthropogenic or climate-related disturbances. Current work, has emphasized controls of methane oxidation associated with rooted aquatic plants. As for the sediment-water interface, we have observed that oxygen availability is a primary limiting factor. Our conclusion is based on several different lines of evidence obtained from in vitro and in situ analyses. First, we have measured the kinetics of methane oxidation by intact plant roots harboring methane-oxidizing bacteria, as well as the kinetics of the methanotrophs themselves. Values for the half-saturation constant (apparent K(sub m)) are approximately 5 microns. These values are roughly equivalent to, or much less than porewater methane concentrations, indicating that uptake is likely saturated with respect to methane, and that some other parameter must limit activity. Methane concentrations in the lacunar spaces at the base of plant stems are also comparable to the half-saturation constants (when expressed as equivalent dissolved concentrations), providing further support for limitation of uptake by parameters other than methane.

  12. In vivo effects of calcium entry blockers on human parathyroid adenoma cells with special reference to calcium sensing ability and the hormone secretion.

    PubMed

    Horikawa, Y; Nakajima, H; Iizuka, K; Imagawa, A; Tomita, K; Shiba, E; Takai, S; Miyagawa, J; Kuwajima, M; Namba, M; Hanafusa, T; Matsuzawa, Y

    1999-01-01

    We evaluated the effects of calcium-entry blockers on parathyroid hormone (PTH) secretion by human parathyroid adenoma cells in vitro. Nifedipine and bamidipine inhibited PTH secretion, while diltiazem had no significant effect. Cytosolic calcium concentrations were measured by use of the calcium-sensitive fluorescent dye fluo-3 with confocal laser scanning microscopy. Nifedipine increased the cytosolic concentration of calcium, whereas diltiazem decreased it. Results suggest that, in parathyroid adenoma cells, regulation of PTH secretion with respect to intracellular calcium concentration would be maintained despite differing response of intracellular calcium concentration following exposure to calcium-entry blockers.

  13. Determinants of the higher order association of the restriction factor TRIM5alpha and other tripartite motif (TRIM) proteins.

    PubMed

    Li, Xing; Yeung, Darwin F; Fiegen, Ann M; Sodroski, Joseph

    2011-08-12

    Many tripartite motif (TRIM) proteins self-associate, forming dimers and higher order complexes. For example, dimers of TRIM5α, a host factor that restricts retrovirus infection, assemble into higher order arrays on the surface of the viral capsid, resulting in an increase in avidity. Here we show that the higher order association of different TRIM proteins exhibits a wide range of efficiencies. Homologous association (self-association) was more efficient than the heterologous association of different TRIM proteins, indicating that specificity determinants of higher order self-association exist. To investigate the structural determinants of higher order self-association, we studied TRIM mutants and chimeras. These studies revealed the following: 1) the RING domain contributes to the efficiency of higher order self-association, which enhances the binding of TRIM5α to the human immunodeficiency virus (HIV-1) capsid; 2) the RING and B-box 2 domains work together as a homologous unit to promote higher order association of dimers; 3) dimerization is probably required for efficient higher order self-association; 4) the Linker 2 region contributes to higher order self-association, independently of effects of Linker 2 changes on TRIM dimerization; and 5) for efficiently self-associating TRIM proteins, the B30.2(SPRY) domain is not required for higher order self-association. These results support a model in which both ends of the core TRIM dimer (RING-B-box 2 at one end and Linker 2 at the other) contribute to the formation of higher order arrays.

  14. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.

    PubMed

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M

    2016-04-12

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption.

  15. Cinacalcet for Hypercalcemia Caused by Pulmonary Squamous Cell Carcinoma Producing Parathyroid Hormone-Related Peptide

    PubMed Central

    Bech, Anneke; Smolders, Koen; Telting, Darryl; de Boer, Hans

    2012-01-01

    Background Current treatments for hypercalcemia caused by lung cell carcinomas producing parathyroid hormone-related peptide (PTH-rp) have limited efficacy, probably because of their lack of effect on PTH-rp secretion. In this case study we explored the efficacy of the calcimimetic cinacalcet as suppressor of PTH-rp production. Patient A 57-year-old male with severe and recurrent hypercalcemia induced by a PTH-rp-producing squamous cell lung carcinoma, stage cT4N3M1b, poorly responding to standard treatments. Results Serum PTH-rp levels were not affected by saline, calcitonin or zoledronate. PTH-rp decreased during chemotherapy and cinacalcet monotherapy. The combination of chemotherapy plus cinacalcet was most effective in rapidly reducing serum calcium and PTH-rp. Conclusion This case study is the first to suggest that cinacalcet may be of value in some cases of PTH-rp-dependent hypercalcemia. Corroborative evidence is needed. PMID:22379470

  16. The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis.

    PubMed

    Squizzato, Alessandro; Van Zaane, Bregje; Gerdes, Victor E A; Büller, Harry R

    2011-02-01

    Endocrine disorders can influence the hemostatic balance. Abnormal coagulation test results have been observed in patients with abnormal hormone levels. The present review updates the available evidence on the influence of pituitary, adrenal, and parathyroid hormones on the coagulation and the fibrinolytic system, and their possible clinical implications. The literature supports a possible relevant clinical effect of the imbalance between coagulation and fibrinolysis on thrombotic events in endogenous Cushing's syndrome. An effect on markers of coagulation and fibrinolysis has been shown for hyperprolactinemia, growth hormone excess or deficiency, exogenous hypercortisolism, pheochromocytoma, primary hyperaldosteronism, and hyperparathyroidism. However, the clinical relevance is still unproven. Until definitive evidence is available, clinicians should be aware of the possibility that endocrine disorders may be risk factors for thrombotic events.

  17. Evolution of Parathyroid Hormone Receptor Family and Their Ligands in Vertebrate

    PubMed Central

    On, Jason S. W.; Chow, Billy K. C.; Lee, Leo T. O.

    2015-01-01

    The presence of the parathyroid hormones in vertebrates, including PTH, PTH-related peptide (PTHrP), and tuberoinfundibular peptide of 39 residues (TIP39), has been proposed to be the result of two rounds of whole genome duplication in the beginning of vertebrate diversification. Bioinformatics analyses, in particular chromosomal synteny study and the characterization of the PTH ligands and their receptors from various vertebrate species, provide evidence that strongly supports this hypothesis. In this mini-review, we summarize recent advances in studies regarding the molecular evolution and physiology of the PTH ligands and their receptors, with particular focus on non-mammalian vertebrates. In summary, the PTH family of peptides probably predates early vertebrate evolution, indicating a more ancient existence as well as a function of these peptides in invertebrates. PMID:25806022

  18. Negative regulation of parathyroid hormone-related protein expression by steroid hormones.

    PubMed

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-04-15

    Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  19. 4D MRI for the Localization of Parathyroid Adenoma: A Novel Method in Evolution.

    PubMed

    Merchavy, Shlomo; Luckman, Judith; Guindy, Michal; Segev, Yoram; Khafif, Avi

    2016-03-01

    The sestamibi scan (MIBI) and ultrasound (US) are used for preoperative localization of parathyroid adenoma (PTA), with sensitivity as high as 90%. We developed 4-dimensional magnetic resonance imaging (4D MRI) as a novel tool for identifying PTAs. Eleven patients with PTA were enrolled. 4D MRI from the mandible to the aortic arch was used. Optimization of the timing of image acquisition was obtained by changing dynamic and static sequences. PTAs were identified in all except 1 patient. In 9 patients, there was a complete match between the 4D MRI and the US and MIBI, as well as with the operative finding. In 1 patient, the adenoma was correctly localized by 4D MRI, in contrast to the US and MIBI scan. The sensitivity of the 4D MRI was 90% and after optimization, 100%. Specificity was 100%. We concluded that 4D MRI is a reliable technique for identification of PTAs, although more studies are needed.

  20. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation

    PubMed Central

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption. PMID:27068606

  1. Development of monoclonal antibodies against parathyroid hormone: genetic control of the immune response to human PTH

    SciTech Connect

    Nussbaum, S.R.; Lin, C.S.; Potts, J.T. Jr.; Rosenthal, A.S.; Rosenblatt, M.

    1985-01-01

    Seventeen monocloanl antibodies against the aminoterminal portion of parathyroid hormone (PTH) were generated by using BALB/c mouse for immunization fully biologically active synthetic human PTH-(1-34) and bovine PTH-(1-84) as immunogens, monoclonal antibody methods, and a solid-phase screening assay. Isotypic analysis of these monoclonal antibodies was performed using affinity purified goat antimouse immunoglobulins specific for IgG heavy chains and ..mu..(IgM). All antibodies were IgM as evidenced by 40 times greater than background activity when 25,000 cpm of /sup 125/I-labelled goat anti-mouse IgM was used as second antibody in a radioimmunoassay.

  2. Mass Spectrometric Immunoassay for Parathyroid Hormone Related Protein (PTHrP)

    SciTech Connect

    Zheng, K.; Rivera, J.D.; Vogel, J.S.; Buchholz, B.A.; Burton, D.W.; Deftos, L.J.; Herold, D.A.; Fitzgerald, R.L.

    2000-06-16

    Many cancers, including prostate, breast and lung express parathyroid hormone related protein (PTHrP). Despite the common tumor overexpression of PTHrP, serum levels of PTHrP are not commonly elevated in affected patients. They postulate that the reasons for the discrepancy between tissue and serum measurements of PTHrP are the inadequate sensitivity and specificity of current PTHrP serum assays. To improve the clinical value of PTHrP serum assays for the cancer patient, they are developing a new generation of novel and ultrasensitive PTHrP serum immunoassays based on immunoaffinity purification, nanospray liquid chromatography tandem mass spectrometry (LC/MS/MS) and accelerator mass spectrometry (AMS).

  3. Identification of RAN1 orthologue associated with sex determination through whole genome sequencing analysis in fig (Ficus carica L.)

    PubMed Central

    Mori, Kazuki; Shirasawa, Kenta; Nogata, Hitoshi; Hirata, Chiharu; Tashiro, Kosuke; Habu, Tsuyoshi; Kim, Sangwan; Himeno, Shuichi; Kuhara, Satoru; Ikegami, Hidetoshi

    2017-01-01

    With the aim of identifying sex determinants of fig, we generated the first draft genome sequence of fig and conducted the subsequent analyses. Linkage analysis with a high-density genetic map established by a restriction-site associated sequencing technique, and genome-wide association study followed by whole-genome resequencing analysis identified two missense mutations in RESPONSIVE-TO-ANTAGONIST1 (RAN1) orthologue encoding copper-transporting ATPase completely associated with sex phenotypes of investigated figs. This result suggests that RAN1 is a possible sex determinant candidate in the fig genome. The genomic resources and genetic findings obtained in this study can contribute to general understanding of Ficus species and provide an insight into fig’s and plant’s sex determination system. PMID:28120935

  4. Identification of RAN1 orthologue associated with sex determination through whole genome sequencing analysis in fig (Ficus carica L.).

    PubMed

    Mori, Kazuki; Shirasawa, Kenta; Nogata, Hitoshi; Hirata, Chiharu; Tashiro, Kosuke; Habu, Tsuyoshi; Kim, Sangwan; Himeno, Shuichi; Kuhara, Satoru; Ikegami, Hidetoshi

    2017-01-25

    With the aim of identifying sex determinants of fig, we generated the first draft genome sequence of fig and conducted the subsequent analyses. Linkage analysis with a high-density genetic map established by a restriction-site associated sequencing technique, and genome-wide association study followed by whole-genome resequencing analysis identified two missense mutations in RESPONSIVE-TO-ANTAGONIST1 (RAN1) orthologue encoding copper-transporting ATPase completely associated with sex phenotypes of investigated figs. This result suggests that RAN1 is a possible sex determinant candidate in the fig genome. The genomic resources and genetic findings obtained in this study can contribute to general understanding of Ficus species and provide an insight into fig's and plant's sex determination system.

  5. Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling.

    PubMed

    McGarvey, Jennifer C; Xiao, Kunhong; Bowman, Shanna L; Mamonova, Tatyana; Zhang, Qiangmin; Bisello, Alessandro; Sneddon, W Bruce; Ardura, Juan A; Jean-Alphonse, Frederic; Vilardaga, Jean-Pierre; Puthenveedu, Manojkumar A; Friedman, Peter A

    2016-05-20

    The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domain-containing proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor.

  6. HUMAN INTERVENTIONS TO CHARACTERIZE NOVEL RELATIONSHIPS BETWEEN THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND PARATHYROID HORMONE

    PubMed Central

    Brown, Jenifer M.; Williams, Jonathan S.; Luther, James M.; Garg, Rajesh; Garza, Amanda E.; Pojoga, Luminita H.; Ruan, Daniel T.; Williams, Gordon H.; Adler, Gail K.; Vaidya, Anand

    2014-01-01

    Observational studies in primary hyperaldosteronism (PA) suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiologic relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without PA. PTH was measured before and after: Study 1) low-dose angiotensin II [AngII] infusion (1 ng/kg/min) and captopril administration (25 mg × 1); Study 2) high-dose AngII infusion (3 ng/kg/min); Study 3) blinded crossover randomization to aldosterone infusion (0.7 µg/kg/hr) and vehicle; and Study 4) blinded randomization to spironolactone (50mg/daily) or placebo for 6 weeks. Infusion of AngII at 1 ng/kg/min acutely increased aldosterone (+148%) and PTH (+10.3%), while AngII at 3 ng/kg/min induced larger incremental changes in aldosterone (+241%) and PTH (+36%) (P<0.01). Captopril acutely decreased aldosterone (−12%) and PTH (−9.7%) (P<0.01). In contrast, aldosterone infusion robustly raised serum aldosterone (+892%) without modifying PTH. However, spironolactone therapy over 6 weeks modestly lowered PTH when compared to placebo (P<0.05). In vitro studies revealed the presence of AngII type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues. We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without PA: the acute modulation of PTH by the RAAS appears to be mediated by AngII, whereas the long-term influence of the RAAS on PTH may involve aldosterone. Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted. PMID:24191286

  7. Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes

    PubMed Central

    1996-01-01

    The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2- terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell. PMID:8922395

  8. Pelvic fracture from major blunt trauma. Outcome is determined by associated injuries.

    PubMed Central

    Poole, G V; Ward, E F; Muakkassa, F F; Hsu, H S; Griswold, J A; Rhodes, R S

    1991-01-01

    Pelvic hemorrhage has been implicated as the cause of death in 50% of patients who die following pelvic fractures. To establish correlates of morbidity and mortality from pelvic fractures due to blunt trauma, we reviewed 236 patients treated during 4 years. The average age of the 144 men and 92 women was 31.5 years, the average Injury Severity Score was 21.3, the average blood requirement was 5 units, and the average hospital stay was 16.8 days. One hundred fifty-two patients (64.4%) were injured in motor vehicle accidents, 33 (14%) had motor vehicle-pedestrian accidents, 16 (6.8%) had crush injuries, 12 (5.1%) each had either motorcycle accidents or falls, and 11 (4.6%) had miscellaneous accidents. Eighteen patients (7.6%) died, with seven (38.9%) deaths due to hemorrhage. Only one death was caused by pelvic hemorrhage. Other deaths were due to hemorrhage from other sites (6), head injury (5), sepsis or multiple-organ failure (4), pulmonary injury (1), and pulmonary embolus (1). None of the septic deaths was related to a pelvic hematoma. Multivariate multiple regression analysis showed that the severity of injury was correlated with indices of severity of pelvic fractures such as fracture site (p less than 0.0001), fracture displacement (p less than 0.005), pelvic stability (p less than 0.0001), and vector of injury (p less than 0.01). However death could not be predicted on the basis of these indices of severity (p greater than 0.28). Of the nine patients who underwent pelvic arteriography, three required embolization of actively bleeding pelvic vessels, but seven had intra-abdominal hemorrhage that required laparotomy, and eight developed a coagulopathy. Massive bleeding from pelvic fractures was uncommon, and the major threat of hemorrhage was from nonpelvic sites. Furthermore, although injury severity was correlated with the severity of the pelvic fracture, hospital outcome was determined by associated injuries and not by the pelvic fracture. PMID:2039283

  9. Influence of Vitamin D and Parathyroid Hormone on Bone and Metabolic Risk in Women with Previous Gestational Diabetes

    PubMed Central

    Serra, Monica C.; Ryan, Alice S.

    2016-01-01

    The purpose of this study was to compare plasma 25-hydroxy vitamin D (25(OH)D) and parathyroid hormone (PTH), VO2max, bone (by DXA), and metabolic outcomes across age and race-matched postmenopausal women (54±1 years; mean±SEM): 1) with previous gestational diabetes (GDM) (32±1 kg/m2; N=17), 2) without previous GDM, but with a similar BMI to GDM (32±1 kg/m2; N=17), and 3) without previous GDM, but with a higher BMI than GDM (36±1 kg/m2; N=17; P<0.01). The prevalence of 25(OH)D insufficiency and deficiency was high (~80%), but not different across groups, while PTH tended to be ~30% lower in women with a history of GDM (P=0.09). Women with a history of GDM had lower HDL cholesterol and higher diastolic blood pressure and fasting and 2-hr glucose levels (by oral glucose tolerance test) (vs. groups 2 and 3; P’s<0.05). Bone mineral density (BMD) tended to be slightly higher in women with prior GDM than the BMI matched women with no prior GDM (P=0.09). Overall, higher PTH was associated with lower femoral neck (r=−0.33) and (r=−0.38) (P’s<0.05), while lower 25(OH)D was associated with lower VO2max (r=0.25, P=0.05) and higher fasting glucose (r=−0.14) and insulin (r=−0.29 (P’s<0.05). We observe that the poor metabolic profiles of postmenopausal women with a history of GDM are independent of 25(OH)D and PTH. However, due to associations between 25(OH)D and PTH with bone and metabolic outcomes, maintaining recommended 25(OH)D and PTH concentrations is important regardless of a previous history of GDM. PMID:26882050

  10. Structural Basis for Parathyroid Hormone-related Protein Binding to the Parathyroid Hormone Receptor and Design of Conformation-selective Peptides

    SciTech Connect

    Pioszak, Augen A.; Parker, Naomi R.; Gardella, Thomas J.; Xu, H. Eric

    2009-12-01

    Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R), a class B G protein-coupled receptor. Both peptides hold clinical interest for their capacities to stimulate bone formation. PTH and PTHrP display different selectivity for two distinct PTH1R conformations, but how their binding to the receptor differs is unclear. The high resolution crystal structure of PTHrP bound to the extracellular domain (ECD) of PTH1R reveals that PTHrP binds as an amphipathic {alpha}-helix to the same hydrophobic groove in the ECD as occupied by PTH, but in contrast to a straight, continuous PTH helix, the PTHrP helix is gently curved and C-terminally 'unwound.' The receptor accommodates the altered binding modes by shifting the side chain conformations of two residues within the binding groove: Leu-41 and Ile-115, the former acting as a rotamer toggle switch to accommodate PTH/PTHrP sequence divergence, and the latter adapting to the PTHrP curvature. Binding studies performed with PTH/PTHrP hybrid ligands having reciprocal exchanges of residues involved in different contacts confirmed functional consequences for the altered interactions and enabled the design of altered PTH and PTHrP peptides that adopt the ECD-binding mode of the opposite peptide. Hybrid peptides that bound the ECD poorly were selective for the G protein-coupled PTH1R conformation. These results establish a molecular model for better understanding of how two biologically distinct ligands can act through a single receptor and provide a template for designing better PTH/PTHrP therapeutics.

  11. Dual-specificity phosphatases are implicated in severe hyperplasia and lack of response to FGF23 of uremic parathyroid glands from rats.

    PubMed

    Román-García, Pablo; Carrillo-López, Natalia; Naves-Díaz, Manuel; Rodríguez, Isabel; Ortiz, Alberto; Cannata-Andía, Jorge B

    2012-04-01

    Phosphate load accelerates the progression of secondary hyperparathyroidism (sHPT). In advanced stages of sHPT, there is a marked hyperplasia and resistance to classical regulatory endocrine factors such as calcium, calcitriol, or fibroblast growth factor 23 (FGF23), which suppresses PTH secretion by an ERK-dependent mechanism. Nephrectomized rats were fed with a high- or normal-phosphorus diet for different periods of time to induce sHPT. Biochemical parameters, parathyroid gland microarrays, quantitative real-time PCR, and immunohistochemistry (ERK/phospho-ERK) were performed. To test the role of dual-specificity phosphatases (Dusp) on parathyroid gland regulation, normal parathyroid glands were cultured with FGF23 and Dusp. Uremic rats fed with a high-phosphorus diet showed more severe sHPT, higher serum FGF23 levels and mortality, and decreased parathyroid Klotho gene expression. In all stages of sHPT, parathyroid microarrays displayed a widespread gene expression down-regulation; only a few genes were overexpressed, among them, Dusp5 and -6. In very severe sHPT, a significant reduction in phospho-ERK (the target of Dusp) and a significant increase of Dusp5 and -6 gene expression were observed. In ex vivo experiments with parathyroid glands, Dusp partially blocked the effect of FGF23 on PTH secretion, suggesting that Dusp might play a role in parathyroid regulation. The overexpression of Dusp and the inactivation of ERK found in the in vivo studies together with the ex vivo results might be indicative of the defense mechanism triggered to counteract hyperplasia, a mechanism that can also contribute to the resistance to the effect of FGF23 on parathyroid gland observed in advanced forms of chronic kidney disease.

  12. Direct Versus Indirect Determination Of Suspended Sediment Associated Metals In A Mining-Influenced Watershed

    EPA Science Inventory

    The differentiation between the concentration of metals associated with suspended sediments and those in the dissolved phase is often of importance in aquatic ecosystems, for such reasons as toxicity evaluation, total maximum daily load calculations, and a better understanding of...

  13. A Methodology for Determining Land Value and Associated Benefits Created from Dredged Material Containment.

    DTIC Science & Technology

    1978-06-01

    site development, in particular the economic aspects, more explicit planning considerations are also warranted in the internal CE study process. The...planning rather than an engineering function. The particulat research effort reported on herein was one ol five aimed at assessing tho economic ...Michael M. McLaughlin, SCS Engineers; Patrick F. Kane, KRS Associates;and Richard Almy, International Association of Assessing Officers. Technical

  14. EVALUATION OF THREE CLEANING METHODS FOR REMOVING ASBESTOS FROM CARPET. DETERMINATION OF AIRBORNE ASBESTOS CONCENTRATIONS ASSOCIATED WITH EACH METHOD

    EPA Science Inventory

    This study was conducted to compare the effectiveness of three cleaning methods to remove asbestos from contaminated carpet and to determine the airborne asbestos concentrations associated with the use of each method. The carpet on which the methods were tested was naturally cont...

  15. Understanding the Association between Future Time Perspective and Self-Regulated Learning through the Lens of Self-Determination Theory

    ERIC Educational Resources Information Center

    de Bilde, Jerissa; Vansteenkiste, Maarten; Lens, Willy

    2011-01-01

    The present cross-sectional research examined a process underlying the positive association between holding an extended future time perspective (FTP) and learning outcomes through the lens of self-determination theory. High school students and university students (N = 275) participated in the study. It was found that students with an extended FTP…

  16. Determining Advanced and Basic Financial Literacy Relations and Overconfidence, and Informative Social Media Association of University Students in Turkey

    ERIC Educational Resources Information Center

    Karaa, Ibrahim E.; Kugu, Tayfun D.

    2016-01-01

    The purposes of the paper are, first, to investigate financial literacy in university students and to determine the relationship between basic and advanced financial literacy; second, to present a positive association between social media usage and financial literacy; third, to examine demographic factors consistent with previous studies; and,…

  17. Parathyroid hormone is a plausible mediator for the metabolic syndrome in the morbidly obese: a cross-sectional study

    PubMed Central

    2011-01-01

    Background The biological mechanisms in the association between the metabolic syndrome (MS) and various biomarkers, such as 25-hydroxyvitamin D (vit D) and magnesium, are not fully understood. Several of the proposed predictors of MS are also possible predictors of parathyroid hormone (PTH). We aimed to explore whether PTH is a possible mediator between MS and various possible explanatory variables in morbidly obese patients. Methods Fasting serum levels of PTH, vit D and magnesium were assessed in a cross-sectional study of 1,017 consecutive morbidly obese patients (68% women). Dependencies between MS and a total of seven possible explanatory variables as suggested in the literature, including PTH, vit D and magnesium, were specified in a path diagram, including both direct and indirect effects. Possible gender differences were also included. Effects were estimated using Bayesian path analysis, a multivariable regression technique, and expressed using standardized regression coefficients. Results Sixty-eight percent of the patients had MS. In addition to type 2 diabetes and age, both PTH and serum phosphate had significant direct effects on MS; 0.36 (95% Credibility Interval (CrI) [0.15, 0.57]) and 0.28 (95% CrI [0.10,0.47]), respectively. However, due to significant gender differences, an increase in either PTH or phosphate corresponded to an increased OR for MS in women only. All proposed predictors of MS had significant direct effects on PTH, with vit D and phosphate the strongest; -0.27 (95% CrI [-0.33,-0.21]) and -0.26 (95% CrI [-0.32,-0.20]), respectively. Though neither vit D nor magnesium had significant direct effects on MS, for women they both affected MS indirectly, due to the strong direct effect of PTH on MS. For phosphate, the indirect effect on MS, mediated through serum calcium and PTH, had opposite sign than the direct effect, resulting in the total effect on MS being somewhat attenuated compared to the direct effect only. Conclusion Our results

  18. Atomic emission spectrometric determination of ephedrine, cinchonine, chlorpheniramine, atropine and diphenhydramine based on formation of ion associates with ammonium reineckate.

    PubMed

    Khalil, S

    1999-12-01

    Ion-associate complexes of ephedrine HCl (I), cinchonine HCl (II), chlorpheniramine maleate (III), atropine sulphate (IV) and diphenhydramine HCl (V) with ammonium reineckate were precipitated and their solubilities were studied as a function of pH, ionic strength and temperature. Saturated solutions of each ion-associate under the optimum precipitation conditions were prepared and the Cr ion content in the supernatant was determined. The solubility products were thus elucidated at different temperatures. A new accurate and precise method using direct current plasma-atomic emission spectrometry for the determination of the investigated drugs in pure solutions and in pharmaceutical preparations is described. The drugs can determined by the present method in the ranges 1.6-52,2.64-85.8,3.12-101.4,5.52-180.4 and 2.72-75.85 microg/ml solutions of I, II, III, IV and V, respectively.

  19. Indirect atomic absorption determination of atropine, diphenhydramine, tolazoline, and levamisole based on formation of ion-associates with potassium tetraiodometrcurate.

    PubMed

    El Ries, M A; Khalil, S

    2001-04-01

    Ion-associate complexes of atropine sulphate (I), diphenhydramine HCl (II), tolazoline HCl (III) and levamisole HCl (IV) with potassium tetraiodomercurate were precipitated and their solubilities were studied as a function of pH, ionic strength and temperature. Saturated solutions of each ion-associate under the optimum precipitation conditions were prepared and the metal ion-content in the supernatant was determined. The solubility products were thus calculated at different temperatures. A new accurate and precise method using atomic absorption spectrometry for the determination of the investigated drugs in pure solutions and in pharmaceutical preparations is described. The drugs can be determined by the present method in the ranges 13.6--138.8, 5.6-58, 3.6--39.6 and 4.8--48 microg/ml solutions of I--IV, respectively.

  20. Considerations in determining the cost of measurement uncertainty associated with dimensional tolerances verification

    NASA Astrophysics Data System (ADS)

    Sanz Lobera, A.; López, M. Villeta; Sebastián Pérez, M. A.

    2012-04-01

    The verification of compliance with a design specification in manufacturing requires the use of metrological instruments to check if the magnitude associated with the design specification is or not according with tolerance range. Such instrumentation and their use during the measurement process, has associated an uncertainty of measurement whose value must be related to the value of tolerance tested. Most papers dealing jointly tolerance and measurement uncertainties are mainly focused on the establishment of a relationship uncertainty-tolerance without paying much attention to the impact from the standpoint of process cost. This paper analyzes the cost-measurement uncertainty, considering uncertainty as a productive factor in the process outcome. This is done starting from a cost-tolerance model associated with the process. By means of this model the existence of a measurement uncertainty is calculated in quantitative terms of cost and its impact on the process is analyzed.

  1. Utility of (18)F-choline photon emission tomography/computed tomography in the diagnosis of parathyroid adenoma.

    PubMed

    Damle, Nishikant Avinash; Tripathi, Madhavi; Behera, Abhishek; Aggarwal, Sameer; Bal, Chandrasekhar; Aggarwal, Shipra; Aggarwal, Vivek; Kandasamy, Devasenathipathi; Taywade, Sameer

    2016-01-01

    Recently, the role of (18)F-choline in the detection of parathyroid adenomas has been reported. At our institution, we are currently studying the role of this tracer in comparison to the standard methoxy-isobutyl-isonitrile.(MIBI) scan with single photon emission tomography/computed tomography. Our initial results show that (18)F-choline is at least as good as 99mTc-MIBI scan. We present here a representative case of a 45-year-old woman with multiple skeletal lytic lesions and a high parathyroid hormone.(PTH) who underwent both these imaging techniques with concordant results, further confirmed by histopathology and postoperative fall in serum PTH levels.

  2. Utility of 18F-choline photon emission tomography/computed tomography in the diagnosis of parathyroid adenoma

    PubMed Central

    Damle, Nishikant Avinash; Tripathi, Madhavi; Behera, Abhishek; Aggarwal, Sameer; Bal, Chandrasekhar; Aggarwal, Shipra; Aggarwal, Vivek; Kandasamy, Devasenathipathi; Taywade, Sameer

    2016-01-01

    Recently, the role of 18F-choline in the detection of parathyroid adenomas has been reported. At our institution, we are currently studying the role of this tracer in comparison to the standard methoxy-isobutyl-isonitrile.(MIBI) scan with single photon emission tomography/computed tomography. Our initial results show that 18F-choline is at least as good as 99mTc-MIBI scan. We present here a representative case of a 45-year-old woman with multiple skeletal lytic lesions and a high parathyroid hormone.(PTH) who underwent both these imaging techniques with concordant results, further confirmed by histopathology and postoperative fall in serum PTH levels. PMID:27385893

  3. Transient response of thyroidectomized pigs to bolus calcium injections and the effect of salmon calcitonin and parathyroid hormone.

    PubMed

    Jaros, G G; Van Hoorn-Hickman, R; Maier, H; Newman, E

    1983-04-01

    The intravenous injection of calcium gluconate (0.11 mM/kg body weight) into conscious thyroidectomized pigs elicits a 30% rise in both ionized and total calcium concentrations of plasma, which return to basal levels within 180 min. The administration of calcitonin (2.5-10 MRC U/kg body weight) reduces this time to 30 to 40 min which is similar to the time obtained in thyroid intact animals. These results suggest that calcitonin may be involved in the fast calcium removal processes and thus in the short-term regulating system of calcium homeostasis. Neither parathyroidectomy nor the administration of parathyroid hormone affected the time for recovery in thyroidectomized pigs, suggesting that the short-term regulation is independent on the parathyroid gland and its hormone.

  4. The effects of parathyroid hormone and estradiol on cadmium accumulation by Madin-Darby canine kidney cells

    SciTech Connect

    Flanagan, J.L.

    1990-01-01

    Chronic exposure to the toxic metal cadmium causes osteomalacia, osteoporosis, increased serum parathyroid hormone, renal stone formation, hypercalciuria and renal tubular dysfunction, reflecting one or more disturbances of calcium homeostasis. Since renal cadmium (Cd[sup 2+]) transport proceeds in both proximal and distal tubules and parathyroid hormone (PTH) regulates calcium reabsorption at distal nephron sites, it was postulated that PTH may also stimulate Cd[sup 2+] transport in distal tubules. Madin-Darby canine kidney (MDCK) cells, which express a distal phenotype including PTH-sensitive adenylate cyclase and calcium transport, were used as the cell model for the present study. Cadmium uptake was measured using [[sup 109]Cd[sup 2+

  5. Cortical activation associated with determination of depth order during transparent motion perception: A normalized integrative fMRI-MEG study.

    PubMed

    Natsukawa, Hiroaki; Kobayashi, Tetsuo

    2015-10-01

    When visual patterns drifting in different directions and/or at different speeds are superimposed on the same plane, observers perceive transparent surfaces on planes of different depths. This phenomenon is known as transparent motion perception. In this study, cortical activities were measured using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) to reveal the cortical dynamics associated with determination of depth order during transparent motion perception. In addition, offline eye movement measurements were performed to determine the latencies of the start of both pursuit eye movements and depth attention that are important in determination of the depth order. MEG and fMRI data were analyzed by a normalized integrative fMRI-MEG method that enables reconstruction of time-varying dipole moments of activated regions from MEG signals. Statistical analysis of fMRI data was performed to identify activated regions. The activated regions were used as spatial constraints for the reconstruction using the integrative fMRI-MEG method. We focused on the period between latencies (216-405 ms) determined by eye movement experiment, which are related to determination of the depth order. The results of integrative analysis revealed that significant neural activities were observed in the visual association area, the human middle temporal area, the intraparietal sulcus, the lateral occipital cortex, and the anterior cingulate cortex between 216 and 405 ms. These results suggest that initial eye movement and accompanying cortical activations during focused duration play an important role in determining the depth order during transparent motion perception.

  6. The Role of Cyclic AMP and Its Relationship to Parathyroid Hormone Response in an In Vitro Model of Chondrogenesis.

    DTIC Science & Technology

    1992-06-01

    examined the effect of bovine parathyroid hoimone 1-34 (bPTH) on an important marker enzyme of chondrocyte maturation, alkaline phosphatase (ALPase), in an...incubated in DMEM, 10% fetal bovine serum and ascorbic acid containing: (1) vehicle; (2) 10-7 to 10-L2M bPTH; (3) forskolin and IBMX; or (4) 10-7 to 10-- 2...A. Effect of bPTH on Alkaline Phosphatase Specific Activity ................................ B. Effect of IBMX and

  7. Pathway-based analysis of GWAs data identifies association of sex determination genes with susceptibility to testicular germ cell tumors.

    PubMed

    Koster, Roelof; Mitra, Nandita; D'Andrea, Kurt; Vardhanabhuti, Saran; Chung, Charles C; Wang, Zhaoming; Loren Erickson, R; Vaughn, David J; Litchfield, Kevin; Rahman, Nazneen; Greene, Mark H; McGlynn, Katherine A; Turnbull, Clare; Chanock, Stephen J; Nathanson, Katherine L; Kanetsky, Peter A

    2014-11-15

    Genome-wide association (GWA) studies of testicular germ cell tumor (TGCT) have identified 18 susceptibility loci, some containing genes encoding proteins important in male germ cell development. Deletions of one of these genes, DMRT1, lead to male-to-female sex reversal and are associated with development of gonadoblastoma. To further explore genetic association with TGCT, we undertook a pathway-based analysis of SNP marker associations in the Penn GWAs (349 TGCT cases and 919 controls). We analyzed a custom-built sex determination gene set consisting of 32 genes using three different methods of pathway-based analysis. The sex determination gene set ranked highly compared with canonical gene sets, and it was associated with TGCT (FDRG = 2.28 × 10(-5), FDRM = 0.014 and FDRI = 0.008 for Gene Set Analysis-SNP (GSA-SNP), Meta-Analysis Gene Set Enrichment of Variant Associations (MAGENTA) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) analysis, respectively). The association remained after removal of DMRT1 from the gene set (FDRG = 0.0002, FDRM = 0.055 and FDRI = 0.009). Using data from the NCI GWA scan (582 TGCT cases and 1056 controls) and UK scan (986 TGCT cases and 4946 controls), we replicated these findings (NCI: FDRG = 0.006, FDRM = 0.014, FDRI = 0.033, and UK: FDRG = 1.04 × 10(-6), FDRM = 0.016, FDRI = 0.025). After removal of DMRT1 from the gene set, the sex determination gene set remains associated with TGCT in the NCI (FDRG = 0.039, FDRM = 0.050 and FDRI = 0.055) and UK scans (FDRG = 3.00 × 10(-5), FDRM = 0.056 and FDRI = 0.044). With the exception of DMRT1, genes in the sex determination gene set have not previously been identified as TGCT susceptibility loci in these GWA scans, demonstrating the complementary nature of a pathway-based approach for genome-wide analysis of TGCT.

  8. Extraversion, neuroticism and verbal reasoning ability as determinants of paired associates learning

    ERIC Educational Resources Information Center

    Allsopp, J. F.; Eysenck, H. J.

    1975-01-01

    Predictions based on theories of verbal learning proposed by Spence and Eysenck were compared by using a noncompetitive list of paired-associates formed from seven synonym pairs, and a competitive list formed by pairing each of the seven S words with a R word with which it was not synonymous. (Editor)

  9. Determination of association constants between steroid compounds and albumins by partial-filling ACE.

    PubMed

    Amundsen, Lotta K; Sirén, Heli

    2007-10-01

    ACE is a popular technique for evaluating association constants between drugs and proteins. However, ACE has not previously been applied to study the association between electrically neutral biomolecules and plasma proteins. We studied the affinity between human and bovine serum albumins (HSA and BSA, respectively) and three neutral endogenous steroid hormones (testosterone, epitestosterone and androstenedione) and two synthetic analogues (methyltestosterone and fluoxymesterone) by applying the partial-filling technique in ACE (PF-ACE). From the endocrinological point of view, the distribution of endogenous steroids among plasma components is of great interest. Strong interactions with albumins suppress the biological activity of steroids. Notable differences in the association constants were observed. In the case of the endogenous steroids, the interactions between testosterone and the albumins were strongest, and those between androstenedione and the albumins were substantially weaker. The association constants, K(b), for testosterone, epitestosterone and androstenedione and HSA at 37 degrees C were 32 100 +/- 3600, 21 600 +/- 1500 and 13 300 +/- 1300 M(-1), respectively, while the corresponding values for the steroids and BSA were 18 800 +/- 1500, 14 000 +/- 400 and 7800 +/- 900 M(-1). Methyltestosterone was bound even more strongly than testosterone, while fluoxymesterone was only weakly bound by the albumins. Finally, the steroids were separated by PF-ACE with HSA and BSA used as resolving components.

  10. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis

    EPA Science Inventory

    ABSTRACT BACKGROUND Anti-neutrophil cytoplasmic autoantibodies (ANCA) specific for myeloperoxidase (MPO) or proteinase 3 (PR3) are detectable in >90% of patients with ANCA-associated vasculitis (AAV). ANCA titers do not correlate well with disease activity. In vivo and in vi...

  11. Determinants among PhD Economists of Membership in a Professional Association.

    ERIC Educational Resources Information Center

    Diamond, Arthur M., Jr.; Haurin, Donald R.

    1994-01-01

    Tested hypotheses about the value of American Economic Association (AEA) membership. An AEA economist is likely to be male, from a highly ranked PhD school, active in publishing research, highly cited for publications, and not in either the business administration or the agriculture subfields. The study involved 913 economists who received their…

  12. Task instructions determine the visuospatial and verbal-spatial nature of number-space associations.

    PubMed

    Georges, Carrie; Schiltz, Christine; Hoffmann, Danielle

    2015-01-01

    Evidence for number-space associations comes from the spatial-numerical association of response codes (SNARC) effect, consisting in faster reaction times to small/large digits with the left/right hand, respectively. Two different proposals are commonly discussed concerning the cognitive origin of the SNARC effect: the visuospatial account and the verbal-spatial account. Recent studies have provided evidence for the relative dominance of verbal-spatial over visuospatial coding mechanisms, when both mechanisms were directly contrasted in a magnitude comparison task. However, in these studies, participants were potentially biased towards verbal-spatial number processing by task instructions based on verbal-spatial labels. To overcome this confound and to investigate whether verbal-spatial coding mechanisms are predominantly activated irrespective of task instructions, we completed the previously used paradigm by adding a spatial instruction condition. In line with earlier findings, we could confirm the predominance of verbal-spatial number coding under verbal task instructions. However, in the spatial instruction condition, both verbal-spatial and visuospatial mechanisms were activated to an equal extent. Hence, these findings clearly indicate that the cognitive origin of number-space associations does not always predominantly rely on verbal-spatial processing mechanisms, but that the spatial code associated with numbers is context dependent.

  13. Experimental determination of the particle motions associated with the low order acoustic modes in enclosures

    NASA Technical Reports Server (NTRS)

    Byrne, K. P.; Marshall, S. E.

    1983-01-01

    A procedure for experimentally determining, in terms of the particle motions, the shapes of the low order acoustic modes in enclosures is described. The procedure is based on finding differentiable functions which approximate the shape functions of the low order acoustic modes when these modes are defined in terms of the acoustic pressure. The differentiable approximating functions are formed from polynomials which are fitted by a least squares procedure to experimentally determined values which define the shapes of the low order acoustic modes in terms of the acoustic pressure. These experimentally determined values are found by a conventional technique in which the transfer functions, which relate the acoustic pressures at an array of points in the enclosure to the volume velocity of a fixed point source, are measured. The gradient of the function which approximates the shape of a particular mode in terms of the acoustic pressure is evaluated to give the mode shape in terms of the particle motion. The procedure was tested by using it to experimentally determine the shapes of the low order acoustic modes in a small rectangular enclosure.

  14. Failed Switching off in the MIBI-Parathyroid Scintigraphy in a Dialyzed Patient with Secondary Hyperparathyroidism Responsive to Cinacalcet Therapy

    PubMed Central

    Bolasco, Piergiorgio; Serra, Alessandra; Loi, Maurizio; Galfré, Andrea; Piga, Mario

    2010-01-01

    The aims of your case report is to show the predictivity of 99mTc-sestamibi (MIBI) scintigraphy and doppler ultrasound imaging on secondary hyperparathyroidism (SHPT) in a patient responsive to calcimimetic treatment. Moreover, it has been reported that calcimimetic has great potential in reducing the volume of the parathyroid gland. On the other hand, the MIBI scintigraphy is considered a crucial diagnostic procedure to monitor the response to therapy in terms of turnover and cellular metabolism; whereas, ultrasound to monitor the volume variation in response to treatment. It is described the case of a 73-year-old man on hemodialysis from 1995 for ESRD. Within 2 years the patient gradually developed SHPT with progressively increased iPTH up to 1,000 ρg/ml. The ultrasound, highlighted the presence of two parathyroid hyperplasia, confirmed by scintigraphy, showing focal increase uptake of sestamibi in the same anatomical areas. As a result of the patient's refusal to perform a parathyroidectomy, cinacalcet, was administered (65 mg overage daily dose). After a year of treatment, there was a striking decrease of iPTH (from 1300 to 57 ρg/ml, −95%); but, on the contrary to expectations, this positive metabolic outcome, was not followed by parathyroid changes in ultrasound and scintigraphic findings. PMID:20652073

  15. Ectopic intrathyroidal thymus accompanied by intrathyroidal parathyroid as a cause of a solitary thyroid nodule in adult.

    PubMed

    Kim, Aeri; Kang, Su Hwan; Bae, Young Kyung

    2014-01-01

    Ectopic intrathyroidal thymic tissue can form a mass lesion within the thyroid gland and has rarely been reported in children. We report a case of intrathyroidal thymus accompanied by an intrathyroidal parathyroid gland in a 29-year-old woman who visited our hospital due to right neck mass diagnosed as metastatic papillary carcinoma by aspiration cytology in an outside hospital. She had a history of right thyroidectomy due to papillary thyroid carcinoma three years ago. Ultrasonographic examination of the left thyroid gland showed a well-defined hyperechoic nodule, which did not show change in size compared with the previous study. She underwent complete thyroidectomy with right neck dissection. Grossly, the left thyroid had a well demarcated pale yellow nodule measuring 0.9 cm in diameter. On microscopic examination, the nodule was composed of mature fat tissue, ectopic thymic tissue with Hassall's corpuscles, and an intrathyroidal parathyroid gland. This is an exceedingly rare case of ectopic intrathyroidal thymus with intrathyroidal parathyroid gland, in an adult.

  16. Binding of ( sup 125 I)iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    SciTech Connect

    Jones, J.I.; Fitzpatrick, L.A. )

    1990-04-01

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with (125I) iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for (125I) iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited (125I) iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes.

  17. Yes-associated protein in the liver: Regulation of hepatic development, repair, cell fate determination and tumorigenesis.

    PubMed

    Nguyen, Quy; Anders, Robert A; Alpini, Gianfranco; Bai, Haibo

    2015-10-01

    The liver is a vital organ that plays a major role in many bodily functions from protein production and blood clotting to cholesterol, glucose and iron metabolism and nutrition storage. Maintenance of liver homeostasis is critical for these essential bodily functions and disruption of liver homeostasis causes various kinds of liver diseases, some of which have high mortality rate. Recent research advances of the Hippo signalling pathway have revealed its nuclear effector, Yes-associated protein, as an important regulator of liver development, repair, cell fate determination and tumorigenesis. Therefore, a precise control of Yes-associated protein activity is critical for the maintenance of liver homeostasis. This review is going to summarize the discoveries on how the manipulation of Yes-associated protein activity affects liver homeostasis and induces liver diseases and the regulatory mechanisms that determine the Yes-associated protein activity in the liver. Finally, we will discuss the potential of targeting Yes-associated protein as therapeutic strategies in liver diseases.

  18. Messenger RNA stability of parathyroid hormone-related protein regulated by transforming growth factor-beta1.

    PubMed

    Sellers, R S; Capen, C C; Rosol, Thomas J

    2002-02-25

    Humoral hypercalcemia of malignancy (HHM), a paraneoplastic syndrome associated with epithelial cancers, including squamous cell carcinoma (SCC), is due to expression and secretion of parathyroid hormone-related protein (PTHrP). Transforming growth factor-beta1 (TGFbeta1), expressed by many tumors, has been demonstrated in vitro to increase the half-life of PTHrP mRNA. In this study, oral squamous carcinoma cells (SCC2/88) had a two-fold increase in PTHrP mRNA stability (from 45 to 90 min) in response to treatment with TGFbeta1. In order to examine the mechanism of TGFbeta1-mediated PTHrP mRNA stability, a cell-free assay of mRNA degradation was utilized in which the degradation of in vitro-transcribed mRNA incubated with cytoplasmic protein extracts from SCC2/88 treated with vehicle or TGFbeta1 was measured. In this assay, full-length PTHrP mRNA was not significantly stabilized in TGFbeta1-treated samples when compared to vehicle treated samples. However, there was a striking (>5-fold) increase in PTHrP mRNA half-life in TGFbeta1-treated samples when PTHrP mRNA lacked the 3'-untranslated region (3'-UTR). In contrast, the degradation of 3'-UTR-truncated PTHrP mRNA using the cell-free assay was not altered in vehicle-treated samples. UV cross-linking of PTHrP mRNA and cytoplasmic proteins from cells treated with either vehicle or TGFbeta1 revealed numerous mRNA-binding proteins. TGFbeta1 treatment resulting in decreased binding of 33, 31, 27, 20 and 18 kDa binding proteins to the terminal coding region. These studies revealed that TGFbeta1-induced PTHrP mRNA stability might be, in part, the result of cis-acting sequences within the coding region of the PTHrP mRNA.

  19. Social determinants of child abuse: evidence of factors associated with maternal abuse from the Egypt demographic and health survey

    PubMed Central

    Antai, Diddy; Braithwaite, Patrick; Clerk., George

    2016-01-01

    Abstract: Background: Child abuse or maltreatment is a significant global public health problem of unknown global prevalence. About 40 million children aged 0 - 14 years require health and social care globally. The prevalence, determinants, and trends of national or global rates of child abuse and maltreatment are largely unknown. Methods: Data for this retrospective cross-sectional study were derived from the 2005 Egyptian Demographic and Health Survey (2005 EDHS), and included 19474 women aged 15-49 years. Multivariate logistic regression analyses by stepwise regression, backward method were used to determine the independent contribution of the possible social determinants of child abuse, with the direction and magnitude of associations expressed as odds ratios (OR) and their 95% confident interval levels (95% CI). Results: Identified determinants of child abuse included exposure to intimate partner violence (IPV), justifying wife beating, exposure to generational IPV, and such factors as younger age of the women, male sex, partners’ lower education, poverty, residence in urban areas, younger children, and residence in households with 3 - 5 children. Conclusions: Experience of IPV, mothers’ justification of wife beating, and generational IPV were associated with elevated odds of child abuse. Findings indicate possible high levels of unmet child protection needs, and stress the need for professionals working with children to employ culturally-sensitive methods in investigating social determinants of child abuse. PMID:26401957

  20. Genome-wide association analysis to identify chromosomal regions determining components of earliness in wheat.

    PubMed

    Le Gouis, J; Bordes, J; Ravel, C; Heumez, E; Faure, S; Praud, S; Galic, N; Remoué, C; Balfourier, F; Allard, V; Rousset, M

    2012-02-01

    The modification of flowering date is considered an important way to escape the current or future climatic constraints that affect wheat crops. A better understanding of its genetic bases would enable a more efficient and rapid modification through breeding. The objective of this study was to identify chromosomal regions associated with earliness in wheat. A 227-wheat core collection chosen to be highly contrasted for earliness was characterized for heading date. Experiments were conducted in controlled conditions and in the field for 3 years to break down earliness in the component traits: photoperiod sensitivity, vernalization requirement and narrow-sense earliness. Whole-genome association mapping was carried out using 760 molecular markers and taking into account the five ancestral group structure. We identified 62 markers individually associated to earliness components corresponding to 33 chromosomal regions. In addition, we identified 15 other significant markers and seven more regions by testing marker pair interactions. Co-localizations were observed with the Ppd-1, Vrn-1 and Rht-1 candidate genes. Using an independent set of lines to validate the model built for heading date, we were able to explain 34% of the variation using the structure and the significant markers. Results were compared with already published data using bi-parental populations giving an insight into the genetic architecture of flowering time in wheat.

  1. The association of waist hip ratio and angiographically determined coronary artery disease.

    PubMed

    Hartz, A; Grubb, B; Wild, R; Van Nort, J J; Kuhn, E; Freedman, D; Rimm, A

    1990-08-01

    Body fat distribution as measured by the ratio of waist circumference to hip circumference (WHR) is now accepted as an important risk factor for a number of diseases. This study evaluated the association of WHR and coronary artery disease (CAD). Measurements included the subjects' height, weight, waist girth, hip girth, significant CAD on coronary angiography, and cholesterol levels. A history of myocardial infarction, angina, diabetes or hypertension was obtained from subject interviews. The subjects were analyzed in two age groups: younger than age 60 (88 men and 39 women) and age 60 or older (85 men and 63 women). For older women the relative odds of CAD comparing women at the 75th percentile of WHR to women at the 25th percentile was 3.67 (P = 0.003), with a 95 percent confidence interval of 1.57-8.57. The relative odds was reduced to 2.80 after adjusting for all other risk factors. WHR was significantly associated with angiographic evidence of CAD in all women combined after adjusting for age (P = 0.0004), but it was not significantly associated with CAD in younger women or in men. The results suggest that in older women the risk of CAD increases with a greater percentage of body fat in the abdomen.

  2. Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Jee, W. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

    1995-01-01

    The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone

  3. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    PubMed

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  4. Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

    NASA Technical Reports Server (NTRS)

    Ma, Y. F.; Jee, W. S. S.; Ke, H. Z.; Lin, B. Y.; Liang, X. G.; Li, M.; Yamamoto, N.

    1994-01-01

    The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates

  5. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    PubMed Central

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the

  6. Individual and combined effects of noise-like whole-body vibration and parathyroid hormone treatment on bone defect repair in ovariectomized mice.

    PubMed

    Matsumoto, Takeshi; Sato, Daisuke; Hashimoto, Yoshihiro

    2016-01-01

    The effectiveness of intermittent administration of parathyroid hormone and exposure to whole-body vibration on osteoporotic fracture healing has been previously investigated, but data on their concurrent use are lacking. Thus, we evaluated the effects of intermittent administration of parathyroid hormone, whole-body vibration, and their combination on bone repair in osteoporotic mice. Noise-like whole-body vibration with a broad frequency range was used instead of conventional sine-wave whole-body vibration at a specific frequency. Mice were ovariectomized at 9 weeks of age and subjected to drill-hole surgery in the right tibial diaphysis at 11 weeks. The animals were divided into four groups (n = 12 each): a control group, and groups treated with intermittent administration of parathyroid hormone, noise-like whole-body vibration, and both. From postoperative day 2, the groups treated with intermittent administration of parathyroid hormone and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were subcutaneously administered parathyroid hormone at a dose of 30 µg/kg/day. The groups treated with noise-like whole-body vibration and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were exposed to noise-like whole-body vibration at a root mean squared acceleration of 0.3g and frequency components of 45-100 Hz for 20 min/day. Following 18 days of interventions, the right tibiae were harvested, and the regenerated bone was analyzed by micro-computed tomography and nanoindentation testing. Compared with the control group, callus volume fraction was 40% higher in groups treated with intermittent administration of parathyroid hormone and 73% higher in groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration, and callus thickness was 35% wider in groups treated with both

  7. Racial differences in the relationship between vitamin D, bone mineral density, and parathyroid hormone in the National Health and Nutrition Examination Survey

    PubMed Central

    Farwell, W. R.; Kermah, D.; Taylor, E. N.

    2011-01-01

    Summary It is unclear whether optimal levels of 25-hydroxyvitamin D (25(OH)D) in whites are the same as in minorities. In adult participants of NHANES, the relationships between 25(OH)D, bone mineral density (BMD), and parathyroid hormone (PTH) differed in blacks as compared to whites and Mexican-Americans, suggesting that optimal 25(OH)D levels for bone and mineral metabolism may differ by race. Introduction Blacks and Hispanics have lower 25-hydroxyvitamin D concentrations than whites. However, it is unclear whether 25(OH)D levels considered “optimal” for bone and mineral metabolism in whites are the same as those in minority populations. Methods We examined the relationships between 25(OH)D and parathyroid hormone in 8,415 adult participants (25% black and 24% Mexican-American) in the National Health and Nutrition Examination Surveys 2003–2004 and 2005–2006; and between 25(OH)D and bone mineral density in 4,206 adult participants (24% black and 24% Mexican-American) in the 2003–2004 sample. Results Blacks and Mexican-Americans had significantly lower 25(OH)D and higher PTH concentrations than whites (P<0.01 for both). BMD significantly decreased (P<0.01) as serum 25(OH)D and calcium intake declined among whites and Mexican-Americans, but not among blacks (P=0.2). The impact of vitamin D deficiency (25 (OH)D≤20 ng/ml) on PTH levels was modified by race/ethnicity (P for interaction, 0.001). Whereas inverse relationships between 25(OH)D and PTH were observed above and below a 25(OH)D level of 20 ng/ml in whites and Mexican-Americans, an inverse association between 25(OH)D and PTH was only observed below this threshold in blacks, with the slope of the relationship being essentially flat (P=0.7) above this cut-point, suggesting that PTH may be maximally suppressed at lower 25(OH)D levels in blacks than in whites or Mexican-Americans. Conclusions The relationships between 25(OH)D, BMD, and PTH may differ by race among US adults. Whether race

  8. Determination of Factors Associated with Natural Soil Suppressivity to Potato Common Scab

    PubMed Central

    Sagova-Mareckova, Marketa; Daniel, Ondrej; Omelka, Marek; Kristufek, Vaclav; Divis, Jiri; Kopecky, Jan

    2015-01-01

    Common scab of potatoes is a disease, which is difficult to manage due to complex interactions of the pathogenic bacteria (Streptomyces spp.) with soil, microbial community and potato plants. In Bohemian-Moravian Highlands in the Czech Republic two sites (Vyklantice and Zdirec) were selected for a study of common scab disease suppressivity. At both sites, a field with low disease severity occurs next to one with high severity and the situation was regularly observed over four decades although all four fields undergo a crop rotation. In the four fields, quantities of bacteria, actinobacteria and the gene txtB from the biosynthetic gene cluster of thaxtomin, the main pathogenicity factor of common scab, were analyzed by real-time PCR. Microbial community structure was compared by terminal fragment length polymorphism analysis. Soil and potato periderm were characterized by contents of carbon, nitrogen, phosporus, sulphur, calcium, magnesium, and iron. Quality of organic matter was assessed by high performance liquid chromatography of soil extracts. The study demonstrated that the suppressive character of the fields is locally specific. At Zdirec, the suppressivity was associated with low txtB gene copies in bulk soil, while at Vyklantice site it was associated with low txtB gene copies in the tuberosphere. The differences were discussed with respect to the effect of abiotic conditions at Zdirec and interaction between potato plant and soil microbial community at Vyklantice. Soil pH, Ca soil content or cation concentrations, although different were not in the range to predict the disease severity. Low severity of common scab was associated with low content of soil C, N, C/N, Ca and Fe suggesting that oligotrophic conditions may be favorable to common scab suppression. PMID:25612311

  9. Using FLOWFFF and HPSEC to determine trace metal-colloid associations in wetland runoff.

    PubMed

    Neubauer, Elisabeth; v d Kammer, Frank; Hofmann, Thilo

    2013-05-15

    Natural organic matter (NOM) and iron colloids can coexist in surface water. These colloids might exhibit different affinities to metals and metalloids. Previously it has been shown, that organic and inorganic colloids in the low nanometer range can be fractionated using Flow Field-Flow Fractionation analyzes (FlowFFF), but it is not yet understood how the presence of inorganic colloids influences results obtained by High Performance Size Exclusion Chromatography (HPSEC). Studies that compare the use of these size-separation techniques for the analyzes of organic and inorganic colloids and associated elements are needed in order to interpret results obtained by either of these methods. Therefore, associations between colloids from a small stream draining a wetland area and a selected range of elements (Fe, Al, Ti, Pb, Cu, Ni, As, U, and Rare Earth Elements (REE)) have been investigated. FlowFFF analyzes and HPSEC analyzes were combined with ultrafiltration, functional group titration and arsenic speciation analysis. NOM and, in a sample with a pH > 5.2, slightly larger iron organo-mineral colloids, were present in the <0.2 μm fraction in the surface water. Both exhibited notably different affinities for trace elements. Cu, Ni, Al, and the REE all showed similar modes (i.e. peak maxima) and size distributions to the NOM, while Pb and As showed a preferential association with iron organo-mineral colloids. It was not possible to differentiate between NOM and iron-organo mineral colloids with HPSEC. The differences in the results regarding the apparent molecular mass distributions obtained by FlowFFF and HPSEC are discussed.

  10. HIV-1 Nef responsiveness is determined by Env variable regions involved in trimer association and correlates with neutralization sensitivity.

    PubMed

    Usami, Yoshiko; Göttlinger, Heinrich

    2013-11-14

    HIV-1 Nef and the unrelated murine leukemia virus glycoGag similarly enhance the infectivity of HIV-1 virions. We now show that the effects of Nef and glycoGag are similarly determined by variable regions of HIV-1 gp120 that control Env trimer association and neutralization sensitivity. Whereas neutralization-sensitive X4-tropic Env proteins conferred high responsiveness to Nef and glycoGag, particles bearing neutralization-resistant R5-tropic Envs were considerably less affected. The profoundly different Nef/glycoGag responsiveness of a neutralization-resistant and a neutralization-sensitive R5-tropic Env could be switched by exchanging their gp120 V1/V2 regions, which also switches their neutralization sensitivity. Within V1/V2, the same determinants governed Nef/glycoGag responsiveness and neutralization sensitivity, indicating that these phenotypes are mechanistically linked. The V1/V2 and V3 regions, which form an apical trimer-association domain, together determined the Nef and glycoGag responsiveness of an X4-tropic Env. Our results suggest that Nef and glycoGag counteract the inactivation of Env spikes with relatively unstable apical trimer-association domains.

  11. A method for determining transmembrane helix association and orientation in detergent micelles using small angle x-ray scattering.

    PubMed Central

    Bu, Z; Engelman, D M

    1999-01-01

    Solution small angle x-ray scattering can be used to study the association of transmembrane proteins solubilized in detergent micelles. We have used the alpha-helical transmembrane domain of the human erythrocyte glycophorin A (GpA) fused to the carboxyl terminus of monomeric staphylococcal nuclease (SN/GpA) as a model system for study. By matching the average electron density of the detergent micelles to that of the buffer solution, the micelle contribution to the small angle scattering vanishes, and the molecular weight and the radius of gyration of the proteins can be determined. SN/GpA has been found to dimerize in a zwitterionic detergent micelle, N-dodecyl-N,N-(dimethylammonio)butyrate (DDMAB), whose average electron density naturally matches the electron density of an aqueous buffer. The dimerization occurs through the transmembrane domains of GpA. With the aid of the nuclease domain scattering, the orientation of the helices within a dimer can be determined to be parallel by radius of gyration analysis. The association constant of a mutant (G83I) that weakens the GpA dimerization has been determined to be 24 microM in the DDMAB environment. The experimental methods established here could be used to apply solution small angle x-ray scattering to studying the association and interactions of other membrane proteins. PMID:10423450

  12. Determinants of bird conservation-action implementation and associated population trends of threatened species.

    PubMed

    Luther, David A; Brooks, Thomas M; Butchart, Stuart H M; Hayward, Matt W; Kester, Marieke E; Lamoreux, John; Upgren, Amy

    2016-12-01

    Conservation actions, such as habitat protection, attempt to halt the loss of threatened species and help their populations recover. The efficiency and the effectiveness of actions have been examined individually. However, conservation actions generally occur simultaneously, so the full suite of implemented conservation actions should be assessed. We used the conservation actions underway for all threatened and near-threatened birds of the world (International Union for Conservation of Nature Red List of Threatened Species) to assess which biological (related to taxonomy and ecology) and anthropogenic (related to geoeconomics) factors were associated with the implementation of different classes of conservation actions. We also assessed which conservation actions were associated with population increases in the species targeted. Extinction-risk category was the strongest single predictor of the type of conservation actions implemented, followed by landmass type (continent, oceanic island, etc.) and generation length. Species targeted by invasive nonnative species control or eradication programs, ex situ conservation, international legislation, reintroduction, or education, and awareness-raising activities were more likely to have increasing populations. These results illustrate the importance of developing a predictive science of conservation actions and the relative benefits of each class of implemented conservation action for threatened and near-threatened birds worldwide.

  13. Determinants of perceived sexism and their role on the association of sexism with mental health.

    PubMed

    Borrell, Carme; Artazcoz, Lucia; Gil-González, Diana; Pérez, Katherine; Pérez, Glòria; Vives-Cases, Carmen; Rohlfs, Izabella

    2011-08-31

    The authors of this study sought to compare the socioeconomic factors related to perceived sexism in employed and non-employed Spanish women and to examine whether the relationship of perceived sexism with mental health outcomes is reduced when such factors are taken into account. Data were taken from the 2006 Spanish Health Survey, including women aged 20-64 years (n=10,927). Multivariate logistic regression models were used to analyze the independent relationships between socioeconomic variables and perceived sexism and also between perceived sexism and poor mental health. In this latter case, socioeconomic variables were included by blocks in the logistic models. Perceived sexism was higher among employed women (3.9% vs. 2.8% among non-employed) and mainly among those in a managerial position (11.35%; adjusted OR: 2.71, 95% CI: 1.30-5.67) and having irregular working hours (5.5%; adjusted OR: 1.60, 95% CI: 1.10-2.34). Socioeconomic and family characteristics were associated with perceived sexism among women. Perceived sexism was associated with poor mental health, and this remained the case when different independent variables were taken into account. These results highlight the importance of taking into account gender discrimination in different aspects of our society, such as work and family organization, and in planning mental health interventions.

  14. Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control

    NASA Astrophysics Data System (ADS)

    Kagami, Haruna; Akutsu, Tatsuya; Maegawa, Shingo; Hosokawa, Hiroshi; Nacher, Jose C.

    2015-10-01

    Deciphering the association between life molecules and human diseases is currently an important task in systems biology. Research over the past decade has unveiled that the human genome is almost entirely transcribed, producing a vast number of non-protein-coding RNAs (ncRNAs) with potential regulatory functions. More recent findings suggest that many diseases may not be exclusively linked to mutations in protein-coding genes. The combination of these arguments poses the question of whether ncRNAs that play a critical role in network control are also enriched with disease-associated ncRNAs. To address this question, we mapped the available annotated information of more than 350 human disorders to the largest collection of human ncRNA-protein interactions, which define a bipartite network of almost 93,000 interactions. Using a novel algorithmic-based controllability framework applied to the constructed bipartite network, we found that ncRNAs engaged in critical network control are also statistically linked to human disorders (P-value of P = 9.8 × 10-109). Taken together, these findings suggest that the addition of those genes that encode optimized subsets of ncRNAs engaged in critical control within the pool of candidate genes could aid disease gene prioritization studies.

  15. Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control.

    PubMed

    Kagami, Haruna; Akutsu, Tatsuya; Maegawa, Shingo; Hosokawa, Hiroshi; Nacher, Jose C

    2015-10-13

    Deciphering the association between life molecules and human diseases is currently an important task in systems biology. Research over the past decade has unveiled that the human genome is almost entirely transcribed, producing a vast number of non-protein-coding RNAs (ncRNAs) with potential regulatory functions. More recent findings suggest that many diseases may not be exclusively linked to mutations in protein-coding genes. The combination of these arguments poses the question of whether ncRNAs that play a critical role in network control are also enriched with disease-associated ncRNAs. To address this question, we mapped the available annotated information of more than 350 human disorders to the largest collection of human ncRNA-protein interactions, which define a bipartite network of almost 93,000 interactions. Using a novel algorithmic-based controllability framework applied to the constructed bipartite network, we found that ncRNAs engaged in critical network control are also statistically linked to human disorders (P-value of P = 9.8 × 10(-109)). Taken together, these findings suggest that the addition of those genes that encode optimized subsets of ncRNAs engaged in critical control within the pool of candidate genes could aid disease gene prioritization studies.

  16. Histopathology of melanosis coli and determination of its associated genes by comparative analysisof expression microarrays

    PubMed Central

    LI, XIAO-AN; ZHOU, YAN; ZHOU, SHU-XIAN; LIU, HAI-RONG; XU, JIN-MEI; GAO, LONG; YU, XIAN-JING; LI, XIAO-HUI

    2015-01-01

    Melanosis coli (MC) refers to the condition characterized by abnormal brown or black pigmentation deposits on the colonic mucosa. However, the histopathological findings and genes associated with the pathogenesis of melanosis coli remain to be fully elucidated. The present study aimed to examine the histopathological features and differentially expressed genes of MC. This involved performing hematoxylin and eosin staining, specific staining and immunohistochemistry on tissues sections, which were isolated from patients diagnosed with MC. DNA expression microarray analysis, western blotting and immunofluorescence assays were performed to analyze the differentially expressed genes of melanosis coli. The results demonstrated that the pigment deposits in MC consisted of lipofuscin. A TUNEL assay revealed that a substantial number of apoptotic cells were present within the macrophages and superficial lamina propria of the colonic epithelium. Expression microarray analysis revealed that the significantly downregulated genes were CYP3A4, CYP3A7, UGT2B11 and UGT2B15 in melanosis coli. Western blotting and immunofluorescence assays indicated that the expression of CYP3A4 in the normal tissue was higher than in the MC tissue. The results of the present study provided a comprehensive description of the histopathological characteristics and pathogenesis of MC and for the first time, to the best of our knowledge, demonstrated that the cytochrome P450-associated genes were significantly downregulated in melanosis coli. This novel information can be used to assist in further investigations of melanosis coli. PMID:26238215

  17. An investigation to determine association between foodborne illness and number of citations in a food establishment.

    PubMed

    Sharkey, Kenneth W; Alam, Mohammad; Mase, William; Ying, Jun

    2012-09-01

    This article analyzes the inspectional data for the food protection program at the Cincinnati Health Department prior to the implementation of a standardization program for food inspections and food inspection training. The main objectives of the authors' study were to assess if current foodborne illness risk factors were associated with different risk classes of food establishments and the relationships between foodborne illness risk factors using non-Centers for Disease Control and Prevention (CDC) foodborne illness risk factors and CDC foodborne illness risk factor criteria. Additionally the authors' study provides information on whether the standardization of staff reduced the number of risk factors at food establishments, reducing the opportunity for a foodborne illness. This research compares the mean number of violations cited per inspection at food establishments of various risk classes. The authors' findings show that both CDC and non-CDC foodborne illness risk factors were positively associated to the risk class of the food establishment; however, more non-CDC than CDC foodborne illness risk factors were cited by the sanitarians at each level of risk class.

  18. Heart rate recovery: autonomic determinants, methods of assessment and association with mortality and cardiovascular diseases.

    PubMed

    Peçanha, Tiago; Silva-Júnior, Natan Daniel; Forjaz, Cláudia Lúcia de Moraes

    2014-09-01

    Cardiovascular disease (CVD) is the primary cause of mortality worldwide. Cardiac autonomic dysfunction seems to be related to the genesis of several CVDs and is also linked to the increased risk of mortality in CVD patients. The quantification of heart rate decrement after exercise - known as heart rate recovery (HRR) - is a simple tool for assessing cardiac autonomic activity in healthy and CVD patients. Furthermore, since The Cleveland Clinic studies, HRR has also been used as a powerful index for predicting mortality. For these reasons, in recent years, the scientific community has been interested in proposing methods and protocols to investigate HRR and understand its underlying mechanisms. The aim of this review is to discuss current knowledge about HRR, including its potential primary and secondary physiological determinants, as well as its role in predicting mortality. Published data show that HRR can be modelled by an exponential curve, with a fast and a slow decay component. HRR may be influenced by population and exercise characteristics. The fast component mainly seems to be dictated by the cardiac parasympathetic reactivation, probably promoted by the deactivation of central command and mechanoreflex inputs immediately after exercise cessation. On the other hand, the slow phase of HRR may be determined by cardiac sympathetic withdrawal, possibly via the deactivation of metaboreflex and thermoregulatory mechanisms. All these pathways seem to be impaired in CVD, helping to explain the slower HRR in such patients and the increased rate of mortality in individuals who present a slower HRR.

  19. Regulation of the osterix (Osx, Sp7) promoter by osterix and its inhibition by parathyroid hormone.

    PubMed

    Barbuto, Richard; Mitchell, Jane

    2013-01-01

    Osterix (Osx, Sp7) is a zinc-finger transcription factor belonging to the specificity protein (Sp) family expressed in cells of the osteoblast lineage in the developing skeleton where it regulates expression of a number of osteoblastic genes. We previously reported inhibition of osterix mRNA and protein by parathyroid hormone (PTH) stimulation of cAMP in osteoblasts. We here show that Osx expression in osteoblasts is regulated by Sp proteins as demonstrated by mithramycin A inhibition of Osx mRNA and OSX protein levels. Mutation of putative transcription factor binding sites within the Osx promoter demonstrated a tandem repeat sequence that selectively binds OSX but not other Sp factors expressed in osteoblasts (Sp1, Sp3, or Tieg (Klf10)). Mutation of either or both the repeat sequences inhibited 90% of the promoter activity and also abrogated some of the PTH-mediated inhibition of the promoter. Previous studies have shown growth factor regulation of Osx expression by MAPK proteins, particularly p38 phosphorylation of OSX that increases its transcriptional activity. PTH stimulation of osteoblasts inhibits MAPK components (ERK, JNK, and p38) but inhibition of Osx mRNA and protein expression by PTH was selectively mimicked by p38 inhibition and expression of constitutively active MKK6, which stimulates p38, blocked PTH inhibition of OSX. Together, our studies suggest that OSX autoregulation is a major mechanism in osteoblasts and that PTH stimulation inhibits osterix by inhibition of p38 MAPK regulation of OSX.

  20. Regulation of the osterix (Osx, Sp7) promoter by osterix and its inhibition by parathyroid hormone

    PubMed Central

    Barbuto, Richard; Mitchell, Jane

    2013-01-01

    Osterix (Osx, Sp7) is a zinc-finger transcription factor belonging to the specificity protein (Sp) family expressed in cells of the osteoblast lineage in the developing skeleton where it regulates expression of a number of osteoblastic genes. We previously reported inhibition of osterix mRNA and protein by parathyroid hormone (PTH) stimulation of cAMP in osteoblasts. We here show that Osx expression in osteoblasts is regulated by Sp proteins as demonstrated by mithramycin A inhibition of Osx mRNA and OSX protein levels. Mutation of putative transcription factor binding sites within the Osx promoter demonstrated a tandem repeat sequence that selectively binds OSX but not other Sp factors expressed in osteoblasts (Sp1, Sp3, or Tieg (Klf10)). Mutation of either or both the repeat sequences inhibited 90% of the promoter activity and also abrogated some of the PTH-mediated inhibition of the promoter. Previous studies have shown growth factor regulation of Osx expression by MAPK proteins, particularly p38 phosphorylation of OSX that increases its transcriptional activity. PTH stimulation of osteoblasts inhibits MAPK components (ERK, JNK, and p38) but inhibition of Osx mRNA and protein expression by PTH was selectively mimicked by p38 inhibition and expression of constitutively active MKK6, which stimulates p38, blocked PTH inhibition of OSX. Together, our studies suggest that OSX autoregulation is a major mechanism in osteoblasts and that PTH stimulation inhibits osterix by inhibition of p38 MAPK regulation of OSX. PMID:23682129

  1. Enterokinase cleavage of fusion proteins for preparation of recombinant human parathyroid hormone 1-34.

    PubMed

    Xiu, Zhao-Yang; Zhou, He-Yue; Yu, Ying; Dai, Jin-Feng; Chen, Chang-Qing

    2002-07-01

    An engineering E.coli strain, BL21 (DE3)/pGEX-4T hPTH (1-34), was constructed by oligonucleotide annealing and PCR amplifying the target gene, then ligating it with pGEX-4T-3 vector and transferring into BL21 host. The yield of soluble fusion protein of GST-hPTH(1-34) expressed from BL21(DE3)/pGEX-4T hPTH(1-34) is about 10 g/L after high-density, high expression culture and purification by affinity chromatography. Following the simple digestion of enterokinase, about 0.6 g/L intact hPTH (1-34) was harvested. The product is checked by HPLC MS and N-terminus sequence analysis. The purified recombinant hPTH(1-34) stimulated adenylate cyclase in rabbit renal cortical cell membranes to exactly the same extent as synthetic human parathyroid hormone standards, indicating that the recombinant product has full biological activity.

  2. Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone

    SciTech Connect

    Pang, P.K.T.; Wang, R.; Shan, J.; Karpinski, E.; Benishin, C.G. )

    1990-01-01

    The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca{sup 2+} channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca{sup 2+} currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca{sup 2+} channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca{sup 2+} in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues PTH can act as an endogenous blocker of Ca{sup 2+} entry.

  3. Canine renal parathyroid hormone receptor is a glycoprotein: characterization and partial purification

    SciTech Connect

    Karpf, D.B.; Arnaud, C.D.; King, K.; Bambino, T.; Winer, J.; Nyiredy, K.; Nissenson, R.A.

    1987-12-01

    Covalent labeling of the canine renal parathyroid hormone receptor with (/sup 125/I)bPTH(1-34) reveals several major binding components that display characteristic consistent with a physiologically relevant adenylate cyclase linked receptor. Through the use of the specific glycosidases neuraminidase and endoglycosidase F and affinity chromatography on lectin-agarose gels, we show here that the receptor is a glycoprotein that contains several complex N-linked carbohydrate chains consisting of terminal sialic acid and penultimate galactose in a ..beta..1,4 linkage to N-acetyl-D-glucosamine. No high mannose chains or O-linked glycans appear to be present. The peptide molecular weight of the deglycosylated labeled receptor is 62,000 (or 58,000 if the mass of bPTH(1-34) is excluded). The binding of (/sup 125/I)bPTH(1-34) to the receptor is inhibited in a dose-dependent fashion by wheat-germ agglutinin, but not by either succinylated wheat-germ agglutinin or Ricinus communis lectin, suggesting that terminal sialic acid may be involved in agonist binding. A combination of lectin affinity chromatography and immunoaffinity chromatography affords a 200-fold purification of the covalently labeled receptor.

  4. Differential sorting of human parathyroid hormone after transduction of mouse and rat salivary glands.

    PubMed

    Adriaansen, J; Perez, P; Goldsmith, C M; Zheng, C; Baum, B J

    2008-10-01

    Gene transfer to salivary glands leads to abundant secretion of transgenic protein into either saliva or the bloodstream. This indicates significant clinical potential, depending on the route of sorting. The aim of this study was to probe the sorting characteristics of human parathyroid hormone (hPTH) in two animal models for salivary gland gene transfer. PTH is a key hormone regulating calcium levels in the blood. A recombinant serotype 5 adenoviral vector carrying the hPTH cDNA was administered to the submandibular glands of mice and rats. Two days after delivery, high levels of hPTH were found in the serum of mice, leading to elevated serum calcium levels. Only low amounts of hPTH were found in the saliva. Two days after vector infusion into rats, a massive secretion of hPTH was measured in saliva, with little secretion into serum. Confocal microscopy showed hPTH in the glands, localized basolaterally in mice and apically in rats. Submandibular gland transduction was effective and the produced hPTH was biologically active in vivo. Whereas hPTH sorted toward the basolateral side in mice, in rats hPTH was secreted mainly at the apical side. These results indicate that the interaction between hPTH and the cell sorting machinery is different between mouse and rat salivary glands. Detailed studies in these two species should result in a better understanding of cellular control of transgenic secretory protein sorting in this tissue.

  5. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug.

    PubMed

    Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A; Schense, Jason C

    2009-03-01

    Regenerative medicine requires innovative therapeutic designs to accommodate high morphogen concentrations in local depots, provide their sustained presence, and enhance cellular invasion and directed differentiation. Here we present an example for inducing local bone regeneration with a matrix-bound engineered active fragment of human parathyroid hormone (PTH(1-34)), linked to a transglutaminase substrate for binding to fibrin as a delivery and cell-invasion matrix with an intervening plasmin-sensitive link (TGplPTH(1-34)). The precursor form displays very little activity and signaling to osteoblasts, whereas the plasmin cleavage product, as it would be induced under the enzymatic influence of cells remodeling the matrix, was highly active. In vivo animal bone-defect experiments showed dose-dependent bone formation using the PTH-fibrin matrix, with evidence of both osteoconductive and osteoinductive bone-healing mechanisms. Results showed that this PTH-derivatized matrix may have potential utility in humans as a replacement for bone grafts or to repair bone defects.

  6. A novel calcium-sensing receptor antagonist transiently stimulates parathyroid hormone secretion in vivo.

    PubMed

    Arey, Brian J; Seethala, Ramakrishna; Ma, Zhengping; Fura, Aberra; Morin, Jennifer; Swartz, Joann; Vyas, Viral; Yang, Wu; Dickson, John K; Feyen, Jean H M

    2005-04-01

    Circulating calcium (Ca(2+)) is a primary regulator of bone homeostasis through its action on PTH secretion. Extracellular Ca(2+) modulates PTH secretion through a cell surface G protein-coupled receptor, the calcium-sensing receptor (CaR). The expression of the CaR suggests a critical role in cellular regulation by calcium in various organs, including parathyroid gland, bone, and kidney. Despite an obvious pharmacological utility for CaR antagonists in the treatment of disease, only a limited number of such classes of compounds exist. We have identified a novel class of small molecules with specific activity at the CaR. This class of compounds is represented by compound 1. It possesses potent antagonist activity at the human CaR with IC(50) values of 64 nm and 230 nm in inhibiting intracellular Ca(2+) flux and inositol phosphate generation in vitro, respectively. When administered to male rats in vivo, compound 1 robustly increased serum PTH levels. The stimulation of PTH secretion was rapid and transient when administered either iv or orally. The pharmacokinetic profile of compound 1 after oral administration revealed that maximal plasma levels of compound were reached within 1 h and the half-life of the compound to be approximately 2 h in rats. These data describe a representative compound of a novel chemical class than previously described allosteric modulators that offer a new avenue for the development of improved treatments of osteoporosis.

  7. Lipoprotein receptor-related protein 6 is required for parathyroid hormone-induced Sost suppression.

    PubMed

    Li, Changjun; Wang, Weishan; Xie, Liang; Luo, Xianghang; Cao, Xu; Wan, Mei

    2016-01-01

    Parathyroid hormone (PTH) suppresses the expression of the bone formation inhibitor sclerostin (Sost) in osteocytes by inducing nuclear accumulation of histone deacetylases (HDACs) to inhibit the myocyte enhancer factor 2 (MEF2)-dependent Sost bone enhancer. Previous studies revealed that lipoprotein receptor-related protein 6 (LRP6) mediates the intracellular signaling activation and the anabolic bone effect of PTH. Here, we investigated whether LRP6 mediates the inhibitory effect of PTH on Sost using an osteoblast-specific Lrp6-knockout (LRP6-KO) mouse model. An increased level of Sost mRNA expression was detected in femur tissue from LRP6-KO mice, compared to wild-type littermates. The number of osteocytes expressing sclerostin protein was also increased in bone tissue of LRP6-KO littermates, indicating a negative regulatory role of LRP6 on Sost/sclerostin. In wild-type littermates, intermittent PTH treatment significantly suppressed Sost mRNA expression in bone and the number of sclerostin(+) osteocytes, while the effect of PTH was much less significant in LRP6-KO mice. Additionally, PTH-induced downregulation of MEF2C and 2D, as well as HDAC changes in osteocytes, were abrogated in LRP6-KO mice. These data indicate that LRP6 is required for PTH suppression of Sost expression.

  8. Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression

    NASA Technical Reports Server (NTRS)

    Lotinun, Sutada; Sibonga, Jean D.; Turner, Russell T.

    2002-01-01

    A mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.

  9. Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: international standards guideline statement.

    PubMed

    Randolph, Gregory W; Dralle, Henning; Abdullah, Hisham; Barczynski, Marcin; Bellantone, Rocco; Brauckhoff, Michael; Carnaille, Bruno; Cherenko, Sergii; Chiang, Fen-Yu; Dionigi, Gianlorenzo; Finck, Camille; Hartl, Dana; Kamani, Dipti; Lorenz, Kerstin; Miccolli, Paolo; Mihai, Radu; Miyauchi, Akira; Orloff, Lisa; Perrier, Nancy; Poveda, Manuel Duran; Romanchishen, Anatoly; Serpell, Jonathan; Sitges-Serra, Antonio; Sloan, Tod; Van Slycke, Sam; Snyder, Samuel; Takami, Hiroshi; Volpi, Erivelto; Woodson, Gayle

    2011-01-01

    Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. Despite the increasing use of IONM, review of the literature and clinical experience confirms there is little uniformity in application of and results from nerve monitoring across different centers. We provide a review of the literature and cumulative experience of the multidisciplinary International Neural Monitoring Study Group with IONM spanning nearly 15 years. The study group focused its initial work on formulation of standards in IONM as it relates to important areas: 1) standards of equipment setup/endotracheal tube placement and 2) standards of loss of signal evaluation/intraoperative problem-solving algorithm. The use of standardized methods and reporting will provide greater uniformity in application of IONM. In addition, this report clarifies the limitations of IONM and helps identify areas where additional research is necessary. This guideline is, at its forefront, quality driven; it is intended to improve the quality of neural monitoring, to translate the best available evidence into clinical practice to promote best practices. We hope this work will minimize inappropriate variations in monitoring rather than to dictate practice options.

  10. Parathyroid hormone 1-34 enhances extracellular matrix deposition and organization during flexor tendon repair.

    PubMed

    Lee, Daniel J; Southgate, Richard D; Farhat, Youssef M; Loiselle, Alayna E; Hammert, Warren C; Awad, Hani A; O'Keefe, Regis J

    2015-01-01

    Parathyroid hormone (PTH) 1-34 is known to enhance fracture healing. Tendon repair is analogous to bone healing in its dependence on the proliferation and differentiation of mesenchymal stem cells, matrix formation, and tissue remodeling.(1,2,3) We hypothesized that PTH 1-34 enhances tendon healing in a flexor digitorum longus (FDL) tendon repair model. C57Bl/6J mice were treated with either intraperitoneal PTH 1-34 or vehicle-control (PBS). Tendons were harvested at 3-28 days for histology, gene expression, and biomechanical testing. The metatarsophalangeal joint range of motion was reduced 1.5-2-fold in PTH 1-34 mice compared to control mice. The gliding coefficient, a measure of adhesion formation, was 2-3.5-fold higher in PTH 1-34 mice. At 14 days post-repair, the tensile strength was twofold higher in PTH 1-34 specimens, but at 28 days there were no differences. PTH 1-34 mice had increased fibrous tissue deposition that correlated with elevated expression of collagens and fibronectin as seen on quantitative PCR. PTH 1-34 accelerated the deposition of reparative tissue but increased adhesion formation.

  11. DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis.

    PubMed

    Wang, Yufeng; Lei, Rong; Zhuang, Xueqian; Zhang, Ning; Pan, Hong; Li, Gang; Hu, Jing; Pan, Xiaoqi; Tao, Qian; Fu, Da; Xiao, Jianru; Chin, Y Eugene; Kang, Yibin; Yang, Qifeng; Hu, Guohong

    2014-04-01

    Bone metastasis is a frequent complication of breast cancer that is often accelerated by TGF-β signaling; however, little is known about how the TGF-β pathway is regulated during bone metastasis. Here we report that deleted in liver ca