Calcium homeostasis after kidney transplantation: a prospective study.
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Adult↗
Biomedical subjects
J Rastad
Publications and source records attributed to J Rastad.
[Transperitoneal endoscopic adrenalectomy already tested].
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Adrenalectomy↗
Clinical and biochemical effects in vivo of monoclonal antitumor antibody in Verner-Morrison's syndrome.
BACKGROUND: Monoclonal antibodies have not been evaluated in metastasizing endocrine tumors, even though these lesions may induce severe morbidity of hormone excess in absence of considerable tumor burden. METHODS: A murine monoclonal antibody of the IgG2a subtype was generated by immunization with dispersed tumor cells from an endocrine pancreatic carcinoma associated with liver and peritoneal metastases as well as a therapy-resistant Verner-Morrison's syndrome. RESULTS: Immunohistochemical staining disclosed selective tissue reactivity of the antibody and conspicuous immunostaining on the surface of the tumor cells. Infusion of 100 mg antibody over 2 days into the common hepatic artery of the patient was accompanied by reduced diarrhea volume until death 6 weeks later and transient elevation of total plasma immunoreactivity for vasoactive intestinal peptide due to large molecular forms of the peptide. Postmortem examination demonstrated disappearance of peritoneal metastases as well as absence of immunostaining for the injected antibody and the transferrin receptor within residual hepatic tumors. CONCLUSION: The results substantiate that symptomatic alleviation and perhaps interference with tumor cell mass may be obtained with monoclonal antibodies in patients with endocrine tumors and that the antiidiotypic immunoglobulin response may play a role herein.
Animals↗
Detection of tumor-specific cytotoxic drug activity in vitro using the fluorometric microculture cytotoxicity assay and primary cultures of tumor cells from patients.
The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was compared with known clinical response patterns, a good correspondence was observed. The results indicate that the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tumors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients.
Antineoplastic Agents↗
Calcium sensing by human medullary thyroid carcinoma cells.
Regulation of the cytoplasmic calcium concentration ([Ca2+]i) was studied in fura-2-loaded C-cells from two human medullary thyroid carcinomas (MTC). K+ depolarization induced sustained rise of [Ca2+]i reversed by verapamil. Elevation of external Ca2+ from 0.5 to 3.0 mM triggered regular oscillations or steady-state increases of [Ca2+]i. In Ca(2+)-deficient medium Sr2+ caused steady-state increase or oscillations of the 340/380 nm fluorescence ratio. The Ca2+ and Sr2+ actions were partially reversible by verapamil. La3+ and Ce3+ elicited transient [Ca2+]i peaks independent of external Ca2+, but no oscillations. The results indicate that human MTC cells express a parathyroid-like Ca2+ sensor coupled to intracellular mobilization and influx of Ca2+. A voltage-dependent Ca2+ influx may be of importance for the oscillations of [Ca2+]i.
Calcium↗
Laparoscopic versus open cholecystectomy: hospitalization, sick leave, analgesia and trauma responses.
Laparoscopic cholecystectomy has rapidly become established as the treatment of choice for cholecystolithiasis. There is very little evidence, however, to support the claimed benefit to patients. In the present study 30 consecutive patients below the age of 65 years without acute cholecystitis and with no signs of common bile duct stones were randomized to laparoscopic or conventional open cholecystectomy. Median (interquartile range) intravenous consumption of pethidine with a patient-controlled injection device between 13 and 24 h after surgery was 125 (62-175) mg in patients who underwent the laparoscopic procedure and 200 (150-250) mg in those who had open operation. Urinary adrenaline and cortisol levels as well as those of plasma glucose, C-reactive protein and interleukin 6 were increased after surgery in both groups of patients, but without any significant difference between them. The mean(s.d.) duration of postoperative hospital stay (2.8(0.8) versus 1.8(0.6) days) and sick leave (24.0(4.4) versus 11.7(4.1) days) was significantly longer with open than laparoscopic cholecystectomy. The findings demonstrate obvious advantages of laparoscopic surgery as regards postoperative pain and convalescence, although factors reflecting the magnitude of trauma did not differ.
Absenteeism↗
A protein involved in calcium sensing of the human parathyroid and placental cytotrophoblast cells belongs to the LDL-receptor protein superfamily.
Monoclonal anti-parathyroid antibodies have been utilized to isolate a single-chain glycoprotein of 500 kDa, which apparently acts as a sensor of the extracellular calcium concentration and is expressed on the surface of human parathyroid, placental, and kidney tubule cells. The present contribution reports the isolation of a cDNA clone encoding this protein in human placenta and subsequent Northern blots confirming the mRNA expression also in human parathyroid and kidney cells. Close similarity in sequence as well as in tissue distribution is demonstrated with the rat Heymann nephritis antigen, a kidney tubule glycoprotein with calcium-binding ability. The 500-kDa protein belongs to the LDL-receptor superfamily of glycoproteins, claimed to function primarily as protein receptors and characterized by functionally important calcium-binding capacity. It is proposed that the currently identified protein constitutes part of a common structure for the sensing of extracellular calcium concentrations and influences calcium homeostasis in different organs.
Base Sequence↗
Different secretory actions of pancreastatin in bovine and human parathyroid cells.
Chromogranin A is an acidic protein that is costored and cosecreted with parathyroid hormone (PTH) from parathyroid cells. Pancreastatin (PST), is derived from chromogranin A, and inhibits secretion from several endocrine/neuroendocrine tissues. Effects of different pancreastatin peptides were investigated on dispersed cells from bovine and human parathyroid glands. Bovine PST(1-47) and bovine PST(32-47) inhibited PTH release from bovine cells in a dose-dependent manner. The former peptide was more potent and suppressed the secretion at 1-100 nM. This inhibition was evident in 0.5 and 1.25 mM, but not in 3.0 mM external Ca2+. Both peptides failed to alter the concentration of cytoplasmic Ca2+ ([Ca2+]i) of bovine cells. Human PST(1-52) and PST(34-52) did not affect PTH release or [Ca2+]i of parathyroid cells from patients with hyperparathyroidism, nor [Ca2+]i of normal human parathyroid cells. Furthermore, bovine PST(1-47) and bovine PST(32-47) failed to alter the secretion of abnormal human parathyroid cells. The study indicates that PST exerts secretory inhibition on bovine but not human parathyroid cells, and that this action does not involve alterations of [Ca2+]i.
Animals↗
Impaired parathyroid hormone release in human immunodeficiency virus infection.
Patients with human immunodeficiency virus type 1 (HIV-1) seropositivity exhibited significantly lower intact serum parathyroid hormone (PTH) values (mean, 13.6 ng/liter; n = 44) than healthy controls (mean, 38.1 ng/liter; p < 0.001; n = 50). The reduction was greater among patients with no or mild immunodeficiency (> 400 x 10(6) CD4+ lymphocytes/ml blood; n = 22) than in those with severe immunodeficiency (< 200 x 10(6) CD4+ lymphocytes/ml blood; n 22; p = 0.03), although total serum calcium was normal in all groups. Patients with severe immunodeficiency demonstrated an inverse correlation between total serum calcium and serum PTH (r2 = 0.367; p < 0.01), which was also present in healthy controls (r2 = 0.482; p < 0.001), but not among the seropositive patients with no or mild immunodeficiency (r2 = 0.017; p = 0.58). Parathyroid cells express a protein recognized by antibodies directed against CD4, the HIV-1 receptor. This implies that these cells may be directly infected with HIV-1 and also interact with circulating autoantibodies against CD4, thus resulting in impaired PTH release.
Autoantibodies↗
Cytoplasmic calcium regulation and the electrocardiogram in patients with primary hyperparathyroidism.
Primary hyperparathyroidism (HPT) is a disease caused by an abnormal cytosolic regulation of calcium concentration [Ca++]i leading to an increased secretion of parathyroid hormone and thereby increased levels of extracellular calcium. It is well known that the QT-interval measured at electrocardiography (ECG) is shortened in HPT subjects. Whether this is due to an abnormal intracellular handling of calcium also in the heart or to the raised extracellular calcium levels is not known. In order to study the extent to which the deranged extra- and intracellular levels of calcium in HPT patients were related to ECG characteristics, [Ca++]i was determined in vitro by microfluorometry in surgery-removed parathyroid cells at extracellular calcium concentrations of 0.5 mM and 30.0 mM and ECG was recorded preoperatively in 42 HPT patients and in 15 subjects operated on for atoxic goitre. Serum calcium and plasma-ionized calcium also were measured preoperatively. The QT-interval and ST-segment duration were both shortened in the HPT patients compared to controls (P < 0.001). [Ca++]i at 3.0 mM extracellular calcium divided by that at 0.5 mM was correlated to the QT-interval, when measured at the onset of the T-wave (QoT, r = 0.39, P < 0.03) and early diastolic phase (end of T-wave to onset of p-wave, r = -0.34, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Multiple endocrine neoplasia type 1. Clinical features and screening.
The clinical and biochemical features of multiple endocrine neoplasia type 1 are presented with a focus on methods for the early detection of the parathyroid, pituitary, and endocrine pancreas. A rationale is provided for early detection of MEN 1-associated abnormalities including a discussion of improved quality of life and reduction of morbidity and mortality.
Genetic Testing↗
Total thyroidectomy in therapy-resistant Graves' disease.
BACKGROUND: Influences of total thyroidectomy have not been evaluated in patients with severe Graves' disease who might respond less satisfactorily to subtotal thyroid resection. METHODS: Thirty-three patients with Graves' disease underwent total thyroidectomy because of persistent endocrine ophthalmopathy (n = 28) or elevated thyrotrophin receptor antibody titers (n = 25) despite a mean of 2 years of thyrostatic therapy. Moreover, six and four patients had undergone radioiodine treatment and subtotal thyroid resection, respectively. Perioperative findings and complications have been investigated, as have influences on endocrine ophthalmopathy and thyrotrophin receptor antibody titers during a mean of 2.5 postoperative years. RESULTS: Total thyroidectomy substantiated mean thyroid weights of 17 gm, 2.3 hours of operating time, and total blood loss of 264 cc. Vocal cord paralysis and vitamin D-treated hypocalcemia occurred in two and three patients, respectively, and invariably persisted less than 6 months. Normalization of elevated thyrotrophin receptor antibody titers occurred in 86% of patients without radioiodine exposure, and stable or improved signs of endocrine ophthalmopathy were found in 96% of patients examined 6 or more months after the operation. CONCLUSIONS: Total thyroidectomy seems to be a surgically safe procedure in complicated Graves' disease and to provide normalization of therapy-resistant thyrotrophin receptor antibody titers. Because favorable influences might also encompass severe endocrine ophthalmopathy, prospective analysis on its efficiency is warranted.
Adult↗
Positron emission tomography with 11C-methionine in hyperparathyroidism.
BACKGROUND: Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism. METHODS: Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained. RESULTS: Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET. CONCLUSIONS: The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.
Adult↗
Relationship between abnormal regulation of cytoplasmic calcium and elevated blood pressure in patients with primary hyperparathyroidism.
Primary hyperparathyroidism (HPT) is characterised by a defective calcium sensitivity of the parathyroid glands. HPT is, furthermore, associated with a high prevalence of hypertension. In the present study BP was measured before operation, during surgery and after operation in 42 HPT patients and in 15 control subjects operated for non-toxic goitre. Parathyroid tissue was removed from all patients and the concentration of cytoplasmic calcium [Ca2+]i was determined in vitro in dispersed single cells by means of microfluometry at extracellular calcium concentrations of 0.5 mM and 3.0 mM. The SBP levels were found to be raised both before (158 +/- 23 (SD) mmHg vs. 144 +/- 24 mmHg in controls, P < 0.05), during surgery (maximal level 167 +/- 22 mmHg vs. 146 +/- 16 mmHg in controls, P < 0.01) and after operation (maximal level 180 +/- 26 mmHg vs. 148 +/- 20 mmHg in controls, P < 0.001) in the HPT subject when compared with controls. SBP during surgery was found to be related to the in vitro measured [Ca2+]i in the parathyroid cells at 3.0 mM extracellular calcium concentration or to the ratio of [Ca2+]i at 3.0 mM-0.5 mM (r = -0.25 and -0.27, respectively; P < 0.05). The degree of suppression of PTH release in vitro at 3.0 mM extracellular calcium was found to be related to both systolic and diastolic BP (r = 0.57 and r = 0.53, respectively; P < 0.05) before surgery. In conclusion, BP was found to be raised in HPT patients both before operation as well as during surgery and after operation.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Regulation of proliferation in JEG-3 cells by a 500-kDa Ca2+ sensor and parathyroid hormone-related protein.
JEG-3 cells are derived from human trophoblasts and demonstrated to express a 500-kDa Ca2+ sensing protein, which elicits biphasic elevations of cytoplasmic Ca2+ concentrations ([Ca2+]i) and mediates Ca2+ regulation of parathyroid hormone-related protein (PTHrP) release from placental cytotrophoblasts. Cytocentrifuged JEG-3 cells were immunostained by monoclonal and polyclonal antiserum toward PTHrP (1-34) and (38-64). Elevation of external Ca2+ from 0.5 to 3.0 mM induced only a sluggish rise in [Ca2+]i and no stimulation of cAMP production despite a more than twofold elevation of PTHrP(1-34) release. Monoclonal antibodies recognizing functionally discrepant epitopes of the Ca2+ sensor protein substantiated uncoupling of this sensor in the Ca(2+)-regulated PTHrP release. Exogenous activation of protein kinase C by a phorbol ester strongly augmented the secretion of PTHrP(1-34), whereby uncoupling of the Ca2+ sensor was partially reversed. This functional differentiation was associated with reduced [3H]thymidine incorporation in JEG-3 cells. Proliferation of these cells was inhibited by 71% upon rise of extracellular Ca2+ from 0.5 to 3.0 mM, and this inhibition was abolished by antibody-mediated interference with the Ca2+ sensor function. PTHrP(1-86) and PTH(1-34) at concentrations up to 10(-7) M decreased proliferation and stimulated the cAMP content of JEG-3 cells. The findings support concomitant Ca2+ sensor and PTH/PTHrP receptor expression in JEG-3 cells, and that Ca2+ inhibits proliferation by actions on the Ca2+ sensor as well as by stimulation of PTHrP release possibly mediating autocrine growth inhibition.
Calcium↗
MHC class I and II antigen expression on parathyroid cells and prospects for their allogenic transplantation.
Homologous parathyroid transplantation has been utilized with rare success in patients suffering from parathyroid hypofunction. Major factors determining the possibility for such transplantation comprise the hitherto essentially unexplored expression and inducibility of MHC class I and II antigens on parathyroid cells. Cryosectioned and dispersed normal human parathyroid tissue displayed no or very low immunohistochemical reactivity for both class I and II antigens on the parenchymal cells, whereas the adenomatous and hyperplastic parenchyma of pathological glands encompassed a higher expression of these antigens. Monolayer culture of parathyroid cells in the presence of IFN-alpha or IFN-gamma induced class I and II antigens on the abnormal but not on the normal parathyroid cells, and no detectable induction of these molecules was obtained by varying the extracellular calcium concentration. The results indicate that normal parathyroid cells may constitute candidates for allogenic transplantation, and that further studies on the modulation of MHC-coded molecules in these cells should facilitate the utility of this potential therapy.
Cell Transplantation↗
Expression of the addisonian autoantigen in human adrenal tumors.
Sera of patients with Addison's disease contain autoantibodies recognizing antigen(s) in the adrenal cortex. In the present study we have examined the antigen expression in normal (n = 6) and pathological human adrenal tissues (n = 24) and also in the human steroid-producing adrenocortical cell line NCI-H295. Sera from two patients with Addison's disease were selected as they strongly stained the human adrenal gland and identified a 54 kDa autoantigen previously demonstrated as 21-hydroxylase. These sera reacted with normal human adrenal cortex (n = 6), all hyperplasias (n = 5) and all the adrenocortical cancers (n = 9), whereas slight or no reactivity was observed in the adenomas without any detectable excess of peripheral steroids (n = 4). Both patient sera reacted in an identical manner with each tissue specimen and they also reacted strongly with the steroid-producing cell line. The data demonstrate that the expression of the Addisonian autoantigen correlates with the functional activity of adrenocortical neoplasms. Furthermore they suggest, that immunohistochemical stainings for steroid-producing enzymes may be clinically useful in the characterization of adrenal lesions.
Addison Disease↗
Incidence, structure, and function of enlarged parathyroid glands discovered accidentally during thyroid surgery.
BACKGROUND: Operation on rare patients with mainly a severe renal stone disease and considerably elevated urinary calcium excretion has substantiated the association of parathyroid gland abnormalities with normocalcemia. This study examines incidence, structure, and functional characteristics of enlarged parathyroid glands of patients with normocalcemia scheduled for thyroid surgery. METHODS: Eleven enlarged parathyroid glands weighing 110 to 1000 mg were discovered in 9 (1.5%) of 594 patients with normocalcemia undergoing thyroid operation. The preoperative total serum calcium concentration was 2.30 to 2.52 mmol/L and less than 2.38 mmol/L in four of the nine patients. Intact serum parathyroid hormone and alkaline phosphatase levels were elevated in only one individual, and all patients showed normal serum creatinine values. RESULTS: All but three of the 11 enlarged parathyroid glands exhibited microscopic abnormality on routine histopathologic examination, including staining for cytoplasmic fat with oil red 0. Immunohistochemical staining with a monoclonal antibody recognizing the functionally important calcium receptor of the parathyroid cell surface and analysis of the calcium-regulated cytoplasmic Ca2+ concentration of dispersed parathyroid cells substantiated that only a single gland of 130 mg had no discernible functional abnormality. CONCLUSIONS: The findings underline the diagnostic difficulties of parathyroid histopathology and support the presence of disturbed parathyroid hormone secretion even in normocalcemic patients with enlarged parathyroid glands. The functional derangement of these glands substantiates the indication for their surgical excision even in patients exhibiting midnormal serum calcium concentrations, although their possible contribution to the development of a clinically overt hyperparathyroidism can only be speculated.
Adult↗