Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (sBGP), a sensitive and specific marker of bone turnover, was measured in 25 patients with primary hyperparathyroidism and in 24 patients with bone metastases with or without hypercalcemia. Despite similar levels of hypercalcemia, sBGP was increased in primary hyperparathyroidism (14.2 +/- 9.6 ng/ml, P less than 0.001), was decreased in malignant hypercalcemia (3.1 +/- 2.8 ng/ml, P less than 0.001), and was normal in patients with bone metastases without hypercalcemia (6.6 +/- 2.7 ng/ml). In primary hyperparathyroidism, sBGP was correlated with serum immuno-reactive parathyroid hormone (r = 0.90), calcium (r = 0.73), and with the adenoma weight (r = 0.79). After parathyroidectomy, sBGP slowly returned to normal values within 2-6 mo, suggesting that sBGP reflects increased bone turnover rather than a direct effect of parathyroid hormone on BGP synthesis at the cell level. An iliac crest biopsy was performed in 11 patients with primary hyperparathyroidism and in 9 cancer patients in a noninvaded area. sBGP was significantly correlated with all parameters reflecting bone formation but not with bone resorption. Patients with bone metastases were analyzed according to the presence or the absence of hypercalcemia. In contrast to normocalcemic patients who had normal sBGP, hypercalcemic patients had decreased sBGP (P less than 0.001) and a lower bone formation at the cellular level (P less than 0.05). Thus, biochemical and histological data suggest that an unknown humoral factor might be responsible for this uncoupling between increased resorption and decreased formation. This uncoupling, rather than local release of calcium by the metastatic process, might be responsible for hypercalcemia in patients with bone metastases.
 ...
PMID:Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry. 348 13

Osteocalcin (or bone Gla protein, BGP) is a non-collagenous vitamin K-dependent protein accounting for 1-2% of the total bone proteins. It represents a specific index of osteoblastic activity and directly reflects the bone turnover. Serum levels of osteocalcin were measured by a radioimmunoassay method. In 40 postmenopausal women with osteoporosis, mean serum BGP levels were lower than the normal range (3.69 +/- 1.35 ng/ml), whereas they significantly increased in 7 patients with osteomalacia (10.48 +/- 3.05 ng/ml), in 12 patients with secondary hyperparathyroidism (11.1 +/- 4.9 ng/ml) and in 41 patients with Paget's disease (12.09 +/- 6.5 ng/ml). Four patients with primary hyperparathyroidism showed very high BGP levels (64.0 +/- 32.3 ng/ml), which strikingly fell after the surgical removal of a parathyroid adenoma. These results confirm that the quantitation of serum osteocalcin is a specific and sensitive method in the diagnosis of bone disease, represents a useful index of bone turnover and is particularly helpful in the follow-up of patients with treated bone disease.
 ...
PMID:Serum osteocalcin radioimmunoassay in bone diseases. 387 67

Among the vitamin K-dependent proteins, characterized by a high content of gamma-carboxyglutamic acid (Gla), one has been identified in bone tissue which has been referred to as osteocalcin (BGP): it has been found in fish, birds, mammalians, primates and in man without significant changes in structure. "In vitro" and "in vivo" studies in the experimental animal and in man have shown that BGP: 1) binds to hydroxyapatite crystals in bone tissue at the maturation of the mineral phase; 2) is probably synthesized by the osteoblasts; 3) circulates as a newly synthesized molecule before binding to bone; 4) shows a rapid turnover rate and is subjected to renal clearance. In conclusion osteocalcin seems to represent a very good index of osteoblast activity. BGP ca be measured in biological fluids by radioimmunoassay. Plasma levels in man range 4-7 ng/ml, they increase in malignant or metabolic disorders (Paget's disease of bone, bone metastases, hyperparathyroidism) and decrease in hypoparathyroidism. In this paper we report the results obtained using a new radioimmunoassay for osteocalcin; the plasma levels were measured in 72 normal adults aged 18-84 years (37 males, 35 females) and in three normal adolescents. The normal range (M +/- SD) was found to be 4,1-7,84 ng/ml. No significant differences were found between males and females, whereas adolescents showed significantly higher values than adults. A positive correlation was found between plasma BGP level and age of subjects in males as well as in females (r = 0,613, p less than 0,001). Fifteen patients with Paget's disease and two with primary hyperparathyroidism showed very high values which fell dramatically in the latter group after surgical removal of parathyroid adenoma. Six cases of secondary hyperparathyroidism were also found to have higher values than normal. The significance of the progressive increase in BGP with increasing age is still to be interpreted.
 ...
PMID:[Osteocalcin]. 633 18

Cushing's syndrome of adrenal origin encompasses different entities: besides the occurrence of adenoma and carcinoma, a not homogeneous group includes the ACTH-independent macro- or micronodular bilateral hyperplasia and the familial pigmented nodular hyperplasia (Carney's syndrome). Moreover, isolated cases of immunological origin and food-dependence have recently described. On clinical grounds no major characteristics may help to identify the adrenal origin of Cushing's syndrome, except for few situations as carcinoma or nodular dysplasia. Laboratory investigations of patients with adrenocortical tumor are based on ACTH and cortisol determinations in basal conditions and in response to high dose dexamethasone and CRH tests. However, isolated diagnostic problems may occur, as the presence of a black adrenocortical adenoma or the uncommon persistence of a circadian rhythmicity of glucocorticoid secretion. The evaluation of new markers of bone turnover (BGP, ICTP) and of collagen turnover (PIIINP) confirms the existence of corticosteroid-induced bone and collagen damages and may also be a useful prognostic index after treatment. Although up to now food-dependent Cushing's syndrome appears to be very rare, the adrenocortical sensitivity to GIP has been investigated in patients with either pituitary Cushing's disease, or clinically silent adrenal masses. No evidence of GIP-dependent cortisol secretion during the peptide infusion or after endogenous stimulation by OGTT was observed in any case. Since the wide availability of sensitive and noninvasive imaging techniques (CT and NMR), in recent years the finding of incidentalomas has become fairly common. In patients with incidentaloma abnormalities of the endocrine function are frequently encountered, and the "preclinical" Cushing's syndrome is increasingly recognized.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clinical and preclinical aspects of adrenal Cushing syndrome]. 765 Dec 81

'de novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of 'de novo' carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the 'de novo' carcinogenesis. 17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labelling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa (P< 0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of 'de novo' colorectal carcinogenesis.
 ...
PMID:Frequent p53 mutation in brain (fetal)-type glycogen phosphorylase positive foci adjacent to human 'de novo' colorectal carcinomas. 1138

'De novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to the colorectal carcinoma. Our previous study demonstrated that brain (fetal)-type glycogen phosphorylase (BGP) positive foci in the transitional mucosa (BGP foci) have frequent p53 mutations and that the distribution of BGP foci has a close relationship with the location of 'de novo' carcinoma. The aims of the present study were to investigate further genetic alterations in the BGP foci and to clarify the mechanism of 'de novo' carcinogenesis. Twenty-eight colorectal carcinomas with invasion into submucosa or superficial muscularis propria without any adenoma component expressing immunoreactive p53 protein were selected from 168 resected specimens. Investigations of the p53, K-ras and APC mutations was performed in the BGP foci, BGP negative colorectal mucosa and 'de novo' carcinoma using PCR-SSCP and DNA squencing. In all 28 cases, immunoreactive BGP was positive in the carcinomas and the BGP foci were observed sporadically in the mucosa adjacent to the carcinoma. No K-ras mutation was observed in either carcinoma or BGP foci in any of the cases. Mutations of p53 and APC were 14 (50.0%) and 9 (32.1%) in 'de novo' carcinomas, and 11 (39.3%) and 1 (3.6%) in BGP foci, respectively. Both p53 and APC mutations were detected in 8 and 1, p53 mutation alone in 6 and 10, APC mutation alone in 1 and 0 out of 28 carcinomas and BGP positive foci, respectively. These results suggest that the BGP foci may play a very important role in the 'de novo' colorectal carcinogenesis from the frequent genetic alterations of p53, and that there may be two major pathways, i.e., the p53-APC pathway and the p53 alone pathway, from the chain of genetic alterations between BGP foci and 'de novo' carcinoma.
 ...
PMID:Genetic pathways of 'de novo' colorectal carcinomas with reference to fetal-type glycogen phosphorylase positive foci. 1246 86