Abstract:
:Osteopetrosis is a rare metabolic bone disease characterized by a generalized increase in skeletal mass. It is inherited in a number of mammalian species, including man, and results from a congenital defect in the development or function of the osteoclasts. The consequent impairment of bone resorption prevents formation of bone marrow cavities, causes delayed or absent tooth eruption and results often in abnormally shaped bone. The pathogenetic defect may be intrinsic either to the osteoclast lineage or to the mesenchymal cells that constitute the microenvironment supporting the development and activation of the osteoclasts. In the first example, the disease can be cured by transplantation of hemopoietic cells. In some cases, bone marrow transplantation has also been successful in curing human osteopetrosis. This, together with the variability in the age of onset and severity of clinical aspects, suggests that a multiplicity of genetic mutations may cause the human disease. In recent years the genetic effects of some osteopetrotic mutations have been identified. This new information has been essential for the understanding of osteoclast biology. Colony stimulating factor 1 (CSF-1), the growth factor for cells of the mononuclear phagocytic system, is also essential for the development of osteoclasts. In the osteopetrotic (op) mouse, no biologically active CSF-1 is synthesized due to a point mutation in the coding region of its gene. This leads to an almost complete lack of osteoclast development and to impaired bone resorption. Altered CSF-1 production seems also to be involved in the toothless (tl) rat osteopetrosis. Recently, the mutation responsible for the microphthalmic (mi) mouse osteopetrosis has been identified in the gene encoding a member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription factors. The mi gene product seems to play a role in the fusion process of osteoclast precursor cells. Finally, osteopetrosis has been the result of experimental gene disruption in mice. Targeted disruption of the c-src proto-oncogene encoding a nonreceptor tyrosine kinase leads to a form of osteopetrosis where osteoclasts are present but inactive. This indicates that pp60c-src, localized primarily on ruffled border membranes and vacuoles of the osteoclasts, is important for osteoclastic function. Disruption of the c-fos proto-oncogene, a major component of the AP-1 transcription factor complex, leads to an osteopetrotic phenotype characterized by a complete absence of osteoclasts. The defect is intrinsic to hemopoietic precursors that are unable to progress beyond an early stage of osteoclast differentiation. In humans, deficiency of carbonic anhydrase II has been identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. A lack of expression of the vacuolar proton pump has been observed in osteoclasts of a patient with craniometaphyseal dysplasia. In conclusion, the disease, although rare, is of great pathophysiological relevance for our understanding of the processes that govern the development and function of osteoclasts.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Felix R,Hofstetter W,Cecchini MGdoi
10.1530/eje.0.1340143subject
Has Abstractpub_date
1996-02-01 00:00:00pages
143-56issue
2eissn
0804-4643issn
1479-683Xjournal_volume
134pub_type
杂志文章,评审abstract::To study the involvement of gonadotropin-releasing hormone (GnRH) in glycosylation of circulating gonadotropin isoforms in anorexia nervosa (AN), 14 amenorrhoic patients with AN, 14 age-matched volunteers in early follicular phase, and five normal-weight re-fed patients with AN were investigated under baseline conditi...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1380076
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVE:The acute decrease in iodide organification in the thyroid in response to excess iodide is termed the acute Wolff-Chaikoff effect and normal organification resumes in spite of continued high plasma iodide concentrations (escape from the acute Wolff-Chaikoff effect). We have recently reported that large doses ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1440139
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVE:Disturbed renal function may play an important role in the clinico-pathological presentation of primary hyperparathyroidism (pHPT). We studied the influence of renal function on the clinico-pathological characteristics of 141 patients (123 women and 18 men) with surgically proven pHPT. METHODS:The 141 patien...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1480597
更新日期:2003-06-01 00:00:00
abstract:Background:Hypophosphataemic rickets (HR) comprise a clinically and genetically heterogeneous group of conditions, defined by renal-tubular phosphate wasting and consecutive loss of bone mineralisation. X-linked hypophosphataemia (XLH) is the most common form, caused by inactivating dominant mutations in PHEX, a gene e...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-20-0275
更新日期:2020-11-01 00:00:00
abstract:CONTEXT:Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified. OBJECTIVE:To investigate CVD risk in adults with CO craniopharyn...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0449
更新日期:2009-11-01 00:00:00
abstract:DESIGN:While androgens and estrogens control glucocorticoid secretion in animal models, how the sex-steroid milieu determines cortisol secretion in humans is less clear. To address this issue, cortisol was measured in archival sera obtained at 10-min intervals for 5 h in 42 healthy men administered double placebo, plac...
journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1530/EJE-10-0149
更新日期:2010-06-01 00:00:00
abstract:UNLABELLED:In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1360401
更新日期:1997-04-01 00:00:00
abstract::Low levels of insulin-like growth factor I (IGF-I) in critical illness are observed despite increased or normal levels of growth hormone (GH). The mechanisms for this apparent GH resistance have not been elucidated. As many of the acute inflammatory responses in critical illness are mediated by the proinflammatory cyt...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1350729
更新日期:1996-12-01 00:00:00
abstract:CONTEXT:A wide range (15-56%) of prevalences of anterior pituitary insufficiency are reported in patients after traumatic brain injury (TBI). However, different study populations, study designs, and diagnostic procedures were used. No data are available on emergency-department-based cohorts of TBI patients. OBJECTIVE:...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0436
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:To assess the individuals' thyroid volume changes after the mandatory nationwide iodine fortification (IF) program in two Danish areas with different iodine intake at baseline (Copenhagen, mild iodine deficiency (ID) and Aalborg, moderate ID). DESIGN:A longitudinal population-based study (DanThyr). METHODS:...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0918
更新日期:2014-03-08 00:00:00
abstract:OBJECTIVE:Activin is a growth and differentiation factor of many cell types, and has recently been implicated in inflammatory processes. Clinical data linking activin and its binding protein, follistatin (FS), are lacking. We measured serum levels of activin and FS in patients diagnosed with septicemia. PATIENTS AND M...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1480559
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVE:Epidemiological studies have shown an increased risk for prostate carcinoma in men with serum IGF-I in the upper part of the age-related reference range. Recombinant human GH (rhGH) is widely used in patients with GH deficiency, usually raising the serum IGF-I levels into the normal range: safety surveillance...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1470059
更新日期:2002-07-01 00:00:00
abstract::Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Tall individuals are usually referred to endocrinologists so that hormonal disorders leading to abnormal growth are excluded. However, the majority of these patients have familial tall stature or constitut...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-16-1054
更新日期:2017-06-01 00:00:00
abstract::We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concen...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1380640
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:Identification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves' disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options. PURPOSE:We performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD i...
journal_title:European journal of endocrinology
pub_type: 杂志文章,meta分析,评审
doi:10.1530/EJE-16-0725
更新日期:2017-01-01 00:00:00
abstract:Background:Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone. Aim:To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus. ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0299
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Glucocorticoids are the mainstay of immunosuppression for active moderate-severe Graves' orbitopathy (GO). AIM:To analyze the response to therapy and the contribution of glucocorticoid receptor (GR) gene polymorphisms to the therapeutic outcome of intravenous glucocorticoids (IVGC) in active moderate-severe...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0611
更新日期:2013-11-22 00:00:00
abstract:OBJECTIVE:Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1530/eje.0.1430577
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:The current guidelines for the management of adrenal incidentaloma advise hormonal and radiological follow-up of patients for 2-5 years after the initial diagnosis. However, the vast majority of adrenal incidentaloma are non-functional benign cortical adenomas that require no treatment, so the routine applica...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-15-0199
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:Affective alterations and poorer quality of life often persist in patients with Cushing's syndrome (CS) in remission. Brain-derived neurotrophic factor (BDNF) regulates the hypothalamic-pituitary-adrenal axis (HPA) and is highly expressed in brain areas controlling mood and response to stress. Our aims were t...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0779
更新日期:2017-02-01 00:00:00
abstract:Objective:Children with Prader-Willi syndrome (PWS) have mild to moderate cognitive impairment. Short-term studies showed positive effects of growth hormone (GH) on cognitive development. This study investigated the effects of 8 years of GH on cognitive development in children with PWS. We also investigated whether sta...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0479
更新日期:2020-04-01 00:00:00
abstract::Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for over 15 years. Early weight- and surface area-based dosing regimens were effective but resulted in supraphysiological levels of IGF1 and increased incidence of side effects. Current practice has moved towards individualised r...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-12-0563
更新日期:2013-02-20 00:00:00
abstract:OBJECTIVES:Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D(3) (25(OH)D(3)) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0545
更新日期:2011-10-01 00:00:00
abstract:CONTEXT AND OBJECTIVE:The precise diagnosis of partially virilised women with 46,XY disorders of sex development (DSD) is often obscure. In practice, this group often comes under the poorly defined, clinically based label of partial androgen insensitivity syndrome (PAIS). In a previous study, we found that 5α-reductase...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-14-0994
更新日期:2015-06-01 00:00:00
abstract::Descent of the testis from an intra-abdominal site in foetal life to an extracorporeal location after birth is a mandatory developmental process to ensure that the mature testis promotes normal spermatogenesis. The two phases of transabdominal and inguinoscrotal descent occur approximately during the first and last th...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-08-0458
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVE:A polymorphism near the promoter region of the IGF-I gene has been associated with serum IGF-I levels, body height and birth weight. In this study, we investigated whether this polymorphism is associated with body composition in young healthy subjects in two cohorts of different generations. DESIGN:Observati...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02101
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVES:Many reports demonstrate improvements in cardiovascular risk factors during GH replacement (rhGH) in adult GH deficiency (GHD). However, it remains to be determined to what extent these changes translate into a reduction of increased cardiovascular morbidity and mortality. The aim of this study was to evalua...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-06-0699
更新日期:2007-04-01 00:00:00
abstract:OBJECTIVE:Vitamin D insufficiency is common in primary hyperparathyroidism (pHPT). Patients with pHPT frequently have a reduced health-related quality of life (HRQoL). Our objectives were to evaluate whether HRQoL in pHPT is associated with vitamin D insufficiency and whether vitamin D supplementation after parathyroid...
journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1530/EJE-14-0757
更新日期:2015-02-01 00:00:00
abstract::Ionomycin, which mobilizes Ca2+, and phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), were used to compare the effects/interactions of Ca2+ and PKC on luteinizing hormone (LH) secretion from pituitaries of intact male and acutely ovariectomized (72 h) rats. Quartered pituitaries from dono...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1300151
更新日期:1994-02-01 00:00:00
abstract:OBJECTIVE:The kisspeptin/GPR54 pathway has been proven to be crucial in the process of puberty onset, yet the polymorphisms in the KISS1 gene and their relationships with central precocious puberty (CPP) have not been investigated. This study was performed to reveal the relationship between the gene and the disease. D...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0061
更新日期:2007-07-01 00:00:00