Parathyroid hormone immunohistochemistry in dogs with primary and secondary hyperparathyroidism: the question of adenoma and primary hyperplasia

In primary hyperparathyroidism, calcium homeostasis is disrupted by excessive synthesis and secretion of parathyroid hormone (PTH), which is usually caused by a solitary adenoma, or less often by nodular hyperplasia or carcinoma of the parathyroid glands. So far, the distinction between these forms of primary hyperparathyroidism has been made by histological examination. In this report clinical and histological findings, including PTH immunohistochemistry, are described in five dogs with primary hyperparathyroidism, three dogs with secondary hyperparathyroidism due to chronic renal failure, and eight control dogs. In the dogs with primary hyperparathyroidism, nodular adenomatous hyperplasia was found in two animals and parathyroid adenoma in three. The dogs with chronic renal failure had diffuse parathyroid gland hyperplasia. The parathyroid glands of the control dogs and the inactive cells surrounding the hyperplastic nodules showed slight to moderate, localized, paranuclear PTH immunolabelling. In the primary nodular and secondary diffuse hyperplasia, all parathyroid cells had a diffuse cytoplasmic PTH labelling pattern, sometimes in combination with localized paranuclear labelling. In parathyroid adenoma, areas with either paranuclear labelling or diffuse cytoplasmic labelling were observed. As both parathyroid adenoma and primary nodular parathyroid gland hyperplasia have characteristics of intrinsic autonomy (i.e., suppression of the remaining endocrine tissue), there would seem to be no functional difference between the two abnormalities. It is argued that primary (multi)nodular hyperplasia is a multiple form of parathyroid adenoma.     

The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism

The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component of this system, e.g. a decrease of CaSR and/or VDR, could result in hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control parathyroids harvested from multi-organ cadaver donors. The small fragments of harvested glands were homogenized and used for Western blot analysis, whereas the remaining tissues underwent routine hematoxylin-eosin staining or immunostaining for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal; some glands displayed a mixed histological phenotype. Western blot analysis revealed a decrease of CaSR and VDR in hyperplasia and adenoma-derived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR- and VDR-immunostained sections revealed a highly differentiated and significantly decreased mean expression of both receptors, which correlated with parathyroid histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is unclear. It presumably results from constant parathyroid stimulation at the stage of S-HPTH, followed by further development of polyclonal autonomy. However, the verification of this thesis requires further study.     

Decreased expression of calcium receptor in parathyroid tissue in patients with hyperparathyroidism secondary to chronic renal failure

The response of parathyroid cells to serum calcium is regulated by a calcium-sensing receptor protein (CaR). In patients with chronic renal failure, hypocalcemia contributes to the parathyroid hyperplasia and increased parathyroid hormone secretion characteristic of secondary hyperparathyroidism (sHPT). However, patients with uremia also display reduced sensitivity to extracellular calcium; this seems to be owing to an alteration of the receptor mechanism. This study examined calcium receptor expression in the parathyroid tissue of patients with sHPT, using immunohistochemical technicques and comparison with normal tissue and parathyroid glands of patients with primary hyperparathyroidism. In all the glands studied, immunostaining was more intense in chief cells than in oxyphilic, transitional, and clear cells. The parathyroid glands of patients with sHPT displayed significantly reduced expression of CaR with respect to morphologically normal ones; a very similar reduction is reported in adenomas. Furthermore, in glands displaying multinodular hyperplasia, expression was less marked in nodule-forming cells than in internodular areas. The decreased expression of calcium receptors in the parathyroid tissue of uremic patients was thought to be owing to the different cell populations present; these parathyroid glands contained predominantly transitional, oxyphilic, and clear cells, which normally express fewer receptors than chief cells, which are more abundant in normal glands.     

PTH、细胞内钙和CaSR在心肌损伤中的“三角关系”

正甲状旁腺激素(parathyroid hormone,PTH)是甲状旁腺细胞分泌的调控机体钙磷代谢的重要激素。近年来,PTH对于心肌的毒性作用开始受到人们关注。钙敏感受体(calcium-sensing receptor,CaSR)是G蛋白偶联家族成员之一,可以感受细胞外钙浓度的细微变化,并通过多种途径调节细胞内钙浓度,进而控制PTH的分泌。CaSR在心肌细胞、     

Review: Molecular and morphological approach of uremia-induced hyperplastic parathyroid gland following direct maxacalcitol injection

The mechanisms explaining the clinical effects of direct maxacalcitol (OCT) injection into the hyperplastic parathyroid gland (PTG) in uremic patients with advanced secondary hyperparathyroidism (SHPT) were investigated by molecular and morphological examination. PTG of uremia-induced SHPT model rats were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (intact-PTH) level, vitamin D and Ca-sensing receptor (VDR and CaSR, respectively) expression levels in PTG, and the calcium (Ca)-PTH response curve were examined; the induction of apoptosis in parathyroid cells (PTC) was also analyzed by the TUNEL method, DNA electrophoresis, and electron microscopic examination. Serum intact-PTH level following DI-OCT significantly decreased. Upregulation of both VDR and CaSR, a clear shift to the left downward in the Ca-PTH curve, and many apoptotic PTCs were observed in the DI-OCT-treated PTGs. However, these findings were not observed in the DI-vehicle-treated PTGs. Moreover, these effects were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulation and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH level in uremia-induced advanced SHPT.     

Chromogranin A and B in parathyroid tissue of cases of primary hyperparathyroidism: an immunohistochemical study

Summary Routinely processed parathyroid tissues from 26 cases with primary hyperparathyroidism (19 adenomas, 7 multiglandular hyperplasia) and 8 normal human parathyroid glands were investigated with antibodies against chromogranin A and B and parathyroid hormone (PTH). Normal parathyroids were immunohistochemically positive for PTH and chromogranin A but negative for chromogranin B. Hyperplastic glands showed a focal staining for PTH and chromogranin A without correlation of the staining pattern on serial sections. Adenomas were either uniformly positive for both PTH and chromogranin A or showed a staining pattern similar to that seen in hyperplastic glands. Focal chromogranin B positivity (less than 10% of cells) was found in 3 cases (1 hyperplastic gland and 2 cases of parathyroid adenoma with an immunohistochemical staining pattern similar to hyperplastic glands). Our immunohistochemical results may support previously published findings that most parathyroid adenomas are monoclonal neoplasms whereas hyperplastic glands are of polyclonal origin.     

Calcium homeostasis,and clinical or subclinical vitamin D deficiency – Can a hypothesis of “intestinal calcistat” explain it all?

The main physiological function of vitamin D is maintenance of calcium homeostasis by its effect on calcium absorption, and bone health in association with parathyroid gland. Vitamin D deficiency (VDD) is defined as serum 25-hydroxy vitamin D (25OHD) levels <20 ng/ml. Vitamin D insufficiency is called when serum 25OHD levels are between 20–29 ng/ml, though existence of this entity has been questioned. Do all subjects with VDD have clinical disease according to this definition? Analysis of published studies suggests that calcium absorption in inversely correlated with serum 25OHD levels and calcium intake. We hypothesize that there exist an intestinal calcistat, which controls the calcium absorption independent of PTH levels. It consists of calcium sensing receptor (CaSR) on intestinal brush border, which senses calcium in intestinal cells and vitamin D system in intestinal cells. CaSR dampens the generation of active vitamin D metabolite in intestinal cells and decrease active transcellular calcium transport. It also facilitates passive paracellular diffusion of calcium in intestine. This local adaptation adjusts the fractional calcium absorption according the body requirement. Failure of local adaptation due to decreased calcium intake, decreased supply of 25OHD, mutation in CaSR or vitamin D system decreases systemic calcium levels and systemic adaptations comes into the play. Systemic adaptations consist of rise in PTH and increase in active vitamin D metabolites. These adaptations lead to bone resorption and maintenance of calcium homeostasis. Not all subjects with varying levels of VDD manifest with secondary hyperparathyroidism and decreased in bone mineral density. We suggest that rise in PTH is first indicator of VDD is rise in PTH along with decrease in BMD depending on duration of VDD. Hence, subjects with any degree of VDD with normal PTH and BMD should not be labeled as vitamin D deficient. These subjects can be called subclinical VDD, and further studies are required to assess beneficial effect of vitamin D supplementation in this subset of population. This hypothesis further highlights pitfalls in treatment of hypoparathyroidism.     

Improvement in histological diagnosis of primary hyperparathyroidism with a monoclonal antiparathyroid antibody

The monoclonal antiparathyroid antibody E11 reacts with a glycoprotein of high molecular weight, which acts as a calcium receptor on the surface of parathyroid cells and mediates calcium regulation of parathyroid hormone (PTH) release. Reduced expression of the calcium receptor has been implicated as a cause of the defect in PTH regulation in the pathological parathyroid parenchyma of patients with hyperparathyroidism (HPT). The present study evaluated the efficacy of immunostainings with the E11 antibody in comparison with routine histopathological methods including staining by the oil red O technique for histological discrimination between normal and pathological parathyroid glands. Parathyroid tissue from euparathyroid individuals invariably presented intense and homogeneous surface staining, with the antibody on virtually all chief cells, while the pathological glands from patients with HPT consistently showed heterogeneous and reduced immunostaining. Even minimally enlarged pathological glands from individuals with mild hypercalcemia and the normal-sized glands associated with adenomas displayed parathyroid chief cells with reduced antibody reactivity. The monoclonal antiparathyroid antibody should constitute a useful tool in parathyroid histopathology not only by its ability to identify the parathyroid tissue, but also by directly demonstrating the functionally normal and abnormal cells within the parathyroid tissue.     

FUNCTIONING OXYPHIL CELL ADENOMA IN A PATIENT WITH SECONDARY HYPERPARATHYROIDISM

A 45-year-old Japanese woman who has been receiving haemodialysis for 13 years suffered from an ectopic calcifying nodule and deformity of the thorax. She was diagnosed as hyperparathyroidism secondary to chronic renal failure. Total parathyroidectomy was performed, and the excised parathyroid glands showed hyperplasia in four and an adenoma in the left upper gland. On the electron microscopic study, the adenoma was composed of oxyphil cells and transitional oxyphil cells, the latter predominating in number. It was revealed from immunohistochemical study that the oxyphil cells in adenoma were strongly stained for parathyroid hormone (PTH). Continuous stimuli to secrete PTH seemed to generate the functioning oxyphil cell adenoma with an ability of PTH production, as well as hyperplasia of parathyroid chief cells. It seems to be the first case of tertiary hyperparathyroidism caused by an oxyphil cell adenoma. Functions of oxyphil cells and transitional oxyphil cells are briefly discussed.     

Hypothesis: the case for quaternary hyperparathyroidism

We report the case of a young woman with hyperparathyroidism due to a large parathyroid adenoma associated with severe vitamin D deficiency. The case is noteworthy for the size of the parathyroid adenoma and for the young age at presentation, and is more typical of the presentation of hyperparathyroidism seen in developing countries where the prevalence of vitamin D deficiency is high. Vitamin D is known to have a suppressive effect on parathyroid cell proliferation and parathyroid hormone synthesis. Vitamin D deficiency may result in a compensatory increase in the secretion of parathyroid hormone (secondary hyperparathyroidism) which involves hyperplasia of all four parathyroid glands. Secondary hyperparathyroidism can become autonomous and this has been termed tertiary hyperparathyroidism, the underlying pathology of which has been variably described in the literature as adenoma formation or four gland hyperplasia. The pathogenesis of parathyroid adenoma formation in vitamin D deficiency remains unclear. It is possible that a proportion of cases represent the coincidence of primary hyperparathyroidism in patients with vitamin D deficiency. Alternatively, we hypothesise that autonomous four gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation and that this should be termed 'quaternary hyperparathyroidism'.     

Functioning oxyphil cell adenoma in a patient with secondary hyperparathyroidism

A 45-year-old Japanese woman who has been receiving haemodialysis for 13 years suffered from an ectopic calcifying nodule and deformity of the thorax. She was diagnosed as hyperparathyroidism secondary to chronic renal failure. Total parathyroidectomy was performed, and the excised parathyroid glands showed hyperplasia in four and an adenoma in the left upper gland. On the electron microscopic study, the adenoma was composed of oxyphil cells and transitional oxyphil cells, the latter predominating in number. It was revealed from immunohistochemical study that the oxyphil cells in adenoma were strongly stained for parathyroid hormone (PTH). Continuous stimuli to secrete PTH seemed to generate the functioning oxyphil cell adenoma with an ability of PTH production, as well as hyperplasia of parathyroid chief cells. It seems to be the first case of tertiary hyperparathyroidism caused by an oxyphil cell adenoma. Functions of oxyphil cells and transitional oxyphil cells are briefly discussed.     

Interleukin-6 production and secretion by human parathyroids

Parathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection of parathyroid tumours. Because IL-6 is also expressed in normal parathyroids and in other endocrine cells (adrenal and islet), we hypothesized that parathyroid tumours might contribute directly to the elevated serum IL-6 levels in patients with hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, and chromogranin-A (an endocrine and neuroendocrine tumour marker) in normal, adenomatous and hyperplastic parathyroids. Using immunofluorescence and confocal microscopy, IL-6 co-localized with PTH and with chromogranin-A in parathyroid cells. All cultured parathyroid tumours secreted IL-6 at levels markedly higher than optimally stimulated peripheral blood mononuclear cells. Supernates from cultured parathyroids stimulated proliferation of an IL-6-dependent cell line, and anti-IL-6 MoAb abolished this stimulatory effect. IL-6 mRNA was documented in cultured parathyroid tumours, cultured normal parathyroids, fresh operative parathyroid tumours and fresh operative normal specimens. In conclusion, these data show that parathyroid tumours and normal parathyroids contain, produce and secrete IL-6. Our findings present a novel pathway by which human parathyroids may contribute markedly to IL-6 production and elevation of serum IL-6 levels in patients with hyperparathyroidism. The physiological relevance of IL-6 production by human parathyroids remains to be determined, but IL-6 secretion by parathyroid tumours may contribute to bone loss and to other multi-system complaints observed in these patients.     

Immunocytochemical staining patterns for parathyroid hormone and chromogranin in parathyroid hyperplasia, adenoma, and carcinoma

Parathyroid glands (PGs) contain less secretory granules with presumably less stored parathyroid hormone (PTH) than many other endocrine glands. Immunocytochemical staining for PTH has been hindered by the lack of commercially available, reliable antibodies against human PTH. By treating deparaffinized tissue sections with an antigen-retrieval procedure, immunocytochemical staining for PTH and chromogranin A (CHA) was performed using commercially available monoclonal antibodies to investigate the functional activity of hyperfunctioning PGs, including chief cell hyperplasia (CCH), adenoma, and carcinoma, compared with that of normal PGs. In normal PGs, PTH and CHA immunostaining was diffusely granular in the chief cell cytoplasm, but was weak in oxyphil cells. The immunostaining in hyperfunctioning PGs was less dense in CCH, and adenomas were less intensely stained than the densely stained peripherally located normal rim. The one carcinoma case studied showed less staining at the periphery and in the mid-portion of the tumor. Thus, immunocytochemical staining for PTH and CHA provides further information on stored, immunoreactive PTH status and will improve functional analysis of hyperfunctioning parathyroid glands.     

Ultrasonography methods in the diagnosis of renal osteodystrophy

Bone disease, i.e. renal osteodystrophy, is commonly seen in patients with chronic renal failure. It encompasses all the disorders of mineral and bone metabolism associated with chronic renal insufficiency, i.e. secondary hyperparathyroidism, retention and accumulation of beta 2 microglobulin and aluminum. The most frequent cause of renal osteodystrophy is secondary hyperthyroidism, with a consequence of high turnover bone disease. Secondary hyperparathyroidism, i.e. increased parathyroid hormone (PTH) secretion and parathyroid gland hyperplasia, develops early in the course of chronic renal insufficiency. Hypocalcemia, phosphate retention and deficiency of calcitriol stimulate PTH synthesis and secretion and parathyroid cell proliferation, i.e. hyperplasia. Parathyroid cell proliferation is initially polyclonal (diffuse hyperplasia), and later it is monoclonal or multiclonal (nodular hyperplasia). Calcitriol receptors as well as calcium-sensing receptors are significantly reduced in parathyroid glands in nodular hyperplasia. Patients with such parathyroid gland hyperplasia are often resistant to vitamin D therapy. A specific form of bone disease is beta 2 amyloidosis. Destructive arthropathy, cystic changes and carpal tunnel syndrome are clinical manifestations of dialysis-related amyloidosis, which is one of the major complications in patients on longterm hemodialysis. Aluminum intoxication leads to the low turnover bone disease and consequential osteomalacia or aplastic bone lesions, the cause of which has not yet been fully clarified. Ultrasound can be a useful, economical and noninvasive method in the evaluation of renal osteodystrophy. Ultrasound waves are very important for noninvasive imaging of soft tissue, especially parathyroid glands, pathologic changes of the joints, and for detection of metastatic calcifications. They are also useful in the evaluation of skeletal status in dialysis patients. Ultrasound waves of a frequency above the limit of human hearing are used in the morphological diagnosis of parathyroid gland. Today, because of its simplicity and non-invasiveness, it is a generally accepted method for the detection of enlarged parathyroid gland in patients with secondary hyperparathyroidism, for the monitoring of pathologic changes, and for making decisions on the method of treatment based on the size and number of parathyroid glands. Ultrasound can distinguish nodal from diffuse parathyroid hyperplasia. Under ultrasound guidance it is possible to perform fine needle aspiration biopsy, to confirm ultrasound findings, and percutaneous inactivation of parathyroid gland (PEI) with alcohol. Ultrasound is useful in the diagnosis of pathologic changes of the musculoskeletal system in patients with beta 2 amyloidosis, to assess the process of its spread, especially in the shoulder joint where the changes are most pronounced (rotator cuff thickness, amyloid deposits as hyperechogenic pads, and detection of fluid in the joint), but it can also be used to examine other joints as well as soft tissue in which metastatic calcifications may occur. Standard ultrasound equipment (pulse-echo) and linear probe of 5-13 MHz are used, also serving for ultrasound examination of the neck, joints and soft tissue. Quantitative bone ultrasonometry is based on different physical characteristics of the ultrasound including: transmission, Speed Of Sound (SOS) in meters/sec and Broad Band Attenuation (BUA) in dB/MHz, and different concepts of the apparatus. These parameters depend on the strength and architecture of the bones and describe better the changes in bone structure in dialysis patients by calculation of the Stiffness Index (QUI), better than the standard bone densitometry by dual-energy x-ray absorptiometry, which only measures bone density. Combined ultrasound measurement of the bone in several locations may be successful in monitoring dialysis patients.     

Clinical Impact of <Emphasis Type="Italic">p27</Emphasis><Superscript><Emphasis Type="Italic">Kip1</Emphasis></Superscript> and CaSR Expression on Primary Hyperparathyroidism

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27^Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27^Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27^Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p <?0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p <?0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p =?0.032). There was a negative association between CaSR expression and body mass index (BMI) (p =?0.027, r =???0.313). There was no significant relationship between p27^Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p >?0.05). The expressions of p27^Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27^Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.     

Parathyroid hormone: radioimmunoassay and clinical interpretation.

A radioimmunoassay for serum immunoreactive parathyroid hormone (iPTH), which has had widespread clinical use for five years, is described in detail. The iPTH results in large groups of patients are reported, and are discussed in relation to the specificity of the assay and in relation to other assays. The assay has excellent precision and is highly proficient in discrimination of groups of patients. Ninety-three percent of 412 patients with surgically proven primary hyperparathyroidism were confidently separated from normal subjects or patients with hypercalcemia owing to other causes, while 86 percent of 160 patients with chronic renal failure and secondary hyperparathyroidism had iPTH values more than 2 S.D. above the normal mean. Results in patients with ectopic hyperparathyroidism were lower than in primary hyperparathyroidism although these groups showed considerable overlap. The antiserum used in this assay for iPTH appears to be specific for the carboxy-terminal region of the secreted or intact form of PTH but recognizes predominantly the secreted form rather than carboxy-terminal fragments believed to be in the circulation. It does not recognize amino terminal fragments. The assay is useful in selective venous catheterization for preoperative localization of hyperfunctioning parathyroid tissue.     

The effect of histamine2 and muscarine receptor antagonists on plasma levels of parathyroid hormone and calcitonin

Summary Long-term administration of cimetidine, a histamine₂ receptor antagonist, has been reported to normalize elevated parathyroid hormone (PTH) concentrations in patients with secondary [1] and primary hyperparathyroidism [2] and even to improve the clinical symptoms. We have compared the effect of cimetidine and pirenzepine on PTH and calcitonin (CT) plasma levels in a short-term trial on patients with secondary hyperparathyroidism. After cimetidine a significant effect on PTH was seen within 30 min lasting 30 min and after pirenzepine, within 60 min and lasting 60 min. The effect on CT was only significant after cimetidine.     

BsmI polymorphism of the vitamin D receptor gene in hyperparathyroid or hypoparathyroid dialysis patients.

Since bone mineral density may be influenced by the polymorphisms of the vitamin D receptor (VDR) gene, we studied whether VDR genotypes might drive the progression toward hyperparathyroidism or hypoparathyroidism in patients with end-stage renal disease. On the basis of their parathyroid hormone (PTH) levels, we divided 99 patients undergoing dialysis into 2 groups: 56 patients with hypoparathyroidism (PTH < 104 pg/mL [< 11 pmol/L]) and 43 with hyperparathyroidism (PTH > 261 pg/mL [> 27.5 pmol/L]). The BB polymorphism was more frequent in patients with hypoparathyroidism (34%) than in patients with hyperparathyroidism (16%), but the difference did not reach statistical significance. Patients with the B allele and BB genotype had a significantly lower dialytic age and serum PTH and alkaline phosphatase levels than patients with the b allele and bb genotype. These results suggest that in end-stage renal disease, the BB genotype may mark a higher risk of developing hypoparathyroidism and diminished bone turnover.     

The expression of parathyroid hormone messenger RNA in normal and abnormal parathyroid tissue.

The distribution and expression of preproparathyroid hormone (PTH) mRNA were investigated in parathyroid tissue from 57 parathyroidectomy specimens. PTH mRNA was detected by in situ hybridization using digoxigenin-labelled oligonucleotide probes. Cell morphology was seen to correlate with PTH mRNA expression. Strong expression of PTH mRNA was confined to cells which on haematoxylin and eosin staining had large vesicular nuclei. These included both vacuolated and non-vacuolated cells. Chief cells with small dark nuclei and scanty cytoplasm had little or no expression. In both adenoma and chief cell hyperplasia, the striking difference from normal was the greatly increased proportion of cells expressing PTH mRNA. In adenomas, the rim of uninvolved parathyroid tissue showed PTH mRNA expression similar to that of normal parathyroid. In hyperplasia, there was frequently concordance of staining within individual nodules. The findings establish morphological criteria for activity of parathyroid tissue and support current concepts of the different pathogenesis of hyperplasia and adenoma. The expression of PTH mRNA in oxyphil change and parathyroid carcinoma was also investigated.     

CaSR抑制剂Calhex231通过PTH-AR途径参与创伤失血性休克大鼠血管低反应性的调节

目的:探讨钙敏感性受体(CaSR)抑制剂Calhex231(Cal)是否通过甲状旁腺素(PTH)-肾上腺素受体(AR)途径参与创伤失血性休克大鼠血管低反应性的调节.方法:检测Cal对创伤失血性休克大鼠血PTH水平的影响,并观察外源给予PTH对正常和休克大鼠血压的影响;Western blot法检测Cal对大鼠肠系膜上动...