摘要:

SUMMARYMany recent studies, only a few of which are reviewed here (see Habener&Pots, 1976, for a detailed summary) have led to considerable clarification concerning critical features of the chemistry, biosynthesis, secretion and mode of action of parathyroid hormone. Certain of the confusion recently experienced in measurements of parathyroid hormone in blood is clearly explained by the heterogeneity arising from various forms of parathyroid hormone arising during biosynthesis and metabolism. Ultimately, as critical featrues of biosynthesis and metabolism of PTH as well as chemical definition of various molecular forms are achieved, considerable refinement in immunoassays should result. These advances in turn should provide better insights into the role of parathyroid dysfunction in various disorders of calcium and skeletal metabolism. From the physiological viewpoint, a clearer appreciation of the homeostatic role of parathyroid hormone in calcium metabolism is emerging as the essential features of biosynthesis, release, metabolism and action of the hormone are uncovered.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03839.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03840.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYThe replacement of the three aromatic amino acids in positions 12, 16 and 19 of human calcitonin (HCT) leucine residues, which occupy the corresponding positions in ultimobranchial, e.g. salmon and eel, calcitonins, increased the hypocalcaemic potency of the peptide, as determined by bioassay on the rat, about 10‐fold. The individual substitutions were not all equally augmentative: leucine (12) enhanced the activity of HCT about 4‐5 times, but leucine (16) and (19) afforded no increase at all. Combination of leucine (12) with a deamino cysteine at the N‐terminmus yielded an analogue 10 times more potnet than HCT. Another analogue containing valine in position 8 in place of methionine as well as the three leucine substituents in position 12, 16 and 19 proved more active than the tri‐leucine analogue, but the additional introduction of tyrosine (22) nearly doubled the hypocalcaemic potency of the latter. The duration of the hypocalcaemic effects of the substituted peptides closely followed the changes in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03841.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYTo determine the mechanism by which calcitonin acutely decreses bone resorption in man, salmon or human calcitonin was administered intravenously to five patients with Paget's disease of bone immediately after an iliac crest bone biopsy. After 30 min an adjacent bone biopsy was taken and both were evaluated by light and electron microscopy. The results indicated that calcitonin both decreases the number of osteoclasts and alters the ultrastructure of these cells. These acute effects of calcitonin on osteociasts confirm findings in other species and provide evidence in man that calcitonin, at least in part, retards bone resorption by inhibiting osteoclastic activity.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03842.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYFour cases of familial bone dysplasia with hyperphosphatasaemia were treated with synthetic human calcitonin. Prior to therapy, all four cases were characterized by marked bone deformity, pain, tenderness and elevated levels of serum alkaline phosphatase and urinary hydroxyproline. Treatment with calcitonin produced in each case a striking clinical, biochemical and radiographic remission. Pain and tenderness was greatly diminished and urinary hydroxyproline and serum alkaline phosphatase levels were significantly decreased. Radiographic regression of the bony abnormalities was apparent as early as 41/2 months after the start of treatment, Prior to therapy bones exhibit no real organization. After calcitonin treatment, the radiographic appearance of a normal cortex and medullary cavity was clearly evident for the first time.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03843.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYThe relationships between the rate of change of metacarpal cortical width, urinary hydroxyproline/creatinine ratio, net absorption of calcium and maturation value of the vaginal smear have been examined in normal post‐menopausal women and crush fracture cases. Rapid bone loss, high bone resorption and low calcium absorption are shown to be associated with poor oestrogen status, with crush fracture cases presenting an exaggerated view of the normal post‐menopausal situat

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03844.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYNon‐endocrine tumours are capable of production of ectopic hormones, precursor molecules subunits and hormone‐related fragments. The measurement of these may provide biochemical markers of maligancy, allowing presymptomatic diagnosis which may lead ultimatley to an improved prognosis for the patient. The study of ectopic humoral syndromes may yield new insights into the nature of cellular differentiation and the fundamental process of malignant cha

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03845.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYThe possibility of a relationship between cyclic AMP formation and metabolic processes in tumours has been investigated. Changes in basal activity and hormone‐responsiveness of adenylate cyclase were demonstrated in plasma membranes and intact cells from pre‐cancerous liver of rats fed a diet containing the carcinogen 3′‐methyl‐4‐dimethylaminoazobenzene. Basal adenylate cyclase activity in hyperplastic parathyroid gland membranes was 200% higher than that in parathyroid adenoma membranes, corresponding with their relative rates of parathyroid hormone secretionin vitro. Membrane adenylate cyclase activity in hypernephromas was consistently 100–300% higher than in adjacent human renal cortex. Furthermore the adenylate cyclase activity of the tumour membranes was not influenced by a wide range of hormones which were effective stimulants in ‘normal’renal cortex membranes. Conversion of 25‐hydroxycholecalciferol to 1,25‐dihydrocholecalciferol could not be demonstrated in either hypernephroma or adjacent renal cortical tissue. However, three of the four hypernephromas tested secreted a bone‐resorbing factor. Cyclic AMP formation was increased by salmon, human and porcine calcitonins in both plasma membranes and intact cells from a poorly differentiated epidermoid cell carcinoma which was itself secreting calcitonin in culture. This phenomenon might be related to a feedback regulation of calcitonin production in this cell line.The observations are consistent with the concept of a relationship between cyclic AMP formation and certain metabolic functions (e.g. hormone prod

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03846.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYMany patients with advanced non‐thyroid malignancies have elevated plasma immunoreactive calcitonin concentrations. Breast and bronchial carcinomas contain immunoreactive calcitonin and an epidermoid bronchial carcinoma has been shown to produce immunoreactive calcitoninin vitro.We have established monolayer cultures of breast carcinomas and eight out of fifteen consecutive carcinomas released immunoreactive calcitonin; some released HCG (human chorionic gonadotrophin) or CEA (carcinoembryonic antigen).In addition, a primary human breast carcinoma has been shown to release and contain calcitonin after being passaged in ‘nude’mice over 1 year.Chromatography of extracts and culture media of a bronchial carcinoma demonstrated that, in contrast with the other tumours, it secreted a from or forms of calcitonin having size, charge and immunological differences when compared to calcitonin M.Preliminary evaluation of plasma immunoreactive calcitonin estimations in patients with breast carcinoma showed that twenty‐three out of twenty‐eight patients with metastatic disease had elevated plasma calcitonin concentrations, whereas only one out of thirteen with localized disease had hi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03847.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

SUMMARYMonolayer tissue culture has been used as a system in which to study aspects of ectopic hormone secretion. Of a series of twenty‐four human bronchial carcinomas, nineteen were successfully established in culture and the supernatant medium from each tested for peptide hormones by radioimmunoassay. Six tumours were found to produce adrenocorticotrophin (ACTH), four to release calcitonin (CT) and one to release both of these hormones. No growth hormone or insulin was detected throughout the series. Netin vitrosynthesis of both ACTH and CT was demonstrated by recovery of more hormone during culture than was originally contained in the explanted tumour tissue. The production of hormone by four out of six proliferative cultures established, and its persistence through many subculture passages, confirms ectopic hormone production as a stable heritable characteristic of some lung tumours. The ability of hormone‐producing bronchial tumour cells to respond to factors known to influence hormone output from normal endocrine cells was tested. ACTH release was stimulated in one tumour by Pitressin and CT in another by gastrin. In addition, the release of CT from the same tumour cell line was shown to be inhibited by the accumulation of high external concentrations of CT as has been reported for normal C‐

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1976.tb03848.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY