Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019621 (Langerhans cell histiocytosis)
 3,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two patients with biopsy proved histiocytosis X, aged 10 months to 14 years (median 2 years) at the time of diagnosis, were observed for 6 months to 13 years (median 4 years). One patient who had received 3000 rads irradiation directly to the hypothalamic-pituitary area had clinical and biochemical evidence of growth hormone deficiency and responded to GH therapy. Thirteen patients had normal stature, normal growth velocity, and no diabetes insipidus. The GH response to insulin-induced hypoglycemia was studied in three of these 13 patients (group 1), in three children with short stature and no diabetes insipidus (group 2), and in five patients with diabetes insipidus but normal stature and growth velocity (group 3). Peak GH responses were normal (greater than 5 micrograms/L) in all patients in groups 1 and 2, but three of the five patients in group 3 had subnormal GH responses to insulin-induced hypoglycemia and to arginine, L-DOPA/propranolol, and exercise. Their growth rates continue to be normal over 6 to 14 years follow-up. Thus, although impaired GH responses were observed in four of the 12 patients tested, true growth failure occurred only in association with direct hypothalamic-pituitary irradiation. This experience and the observation that GH deficiency was diagnosed in fewer than 1% of children with histiocytosis in Canada during a 15-year period (accounting for less than 1% of all children with GH deficiency) suggest that classic GH deficiency is not a common complication of histiocytosis unless direct hypothalamic-pituitary irradiation has been given.
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PMID:Growth hormone deficiency in patients with histiocytosis X. 348 29

We evaluated the GH-releasing effect of GHRH plus arginine (ARG) in 36 patients (22 males and 14 females) with acquired GH deficiency including idiopathic inflammatory pituitary stalk thickness (n = 15), Langerhans cell histiocytosis (LCH) affecting the hypothalamic-pituitary area (n = 11), and craniopharyngioma (n = 10). All of the patients (mean age, 9.6 +/- 3.1 yr; range, 5.6-20.8) showed GH response less than 10 microg/liter after 2 pharmacological stimuli and were tested with GHRH plus ARG at a mean age of 11.2 +/- 4.1 yr. Twenty-nine patients had vasopressin deficiency, 10 had TSH deficiency, 8 had gonadotropin deficiency, and 4 had ACTH deficiency. The median peak GH response to insulin test was 2.1 microg/liter (range, 1.1-2.9), whereas it was 1.5 microg/liter (range, 1.3-2.4) after ARG. The median peak GH response to insulin was significantly lower in the patients with craniopharyngioma (1.4 microg/liter; range, 0.8-1.7) than in the patients with idiopathic pituitary stalk thickness (2.2 microg/liter; range, 1.0-2.4) or with LCH (2.6 microg/liter; range 2.0-4.3, P = 0.02). The median peak GH response to ARG was significantly lower in the patients with idiopathic inflammatory pituitary stalk thickness (1.3 microg/liter; range, 0.8-1.8) than in those with craniopharyngioma (1.5 microg/liter; range, 1.1-1.6) or with LCH (2.8 microg/liter; range, 1.9-3.2, P = 0.00007). The median peak GH response after GHRH plus ARG was significantly lower in the overall patient population (8.3 microg/liter; range, 4.4-28.4) than in the age-matched controls (49.8 microg/liter; range, 39.9-81.6, P < 0.00001). The median peak GH response was significantly lower in the patients with craniopharyngioma (4.6 microg/liter; range, 3.6-6.3) than in those with LCH (8.9 microg/liter; range, 4.4-28.4) or with idiopathic pituitary stalk thickness (12.6 microg/liter, range, 6.4-24, P = 0.07). Ten patients had a GH response of more than 20 microg/liter after GHRH plus ARG. There was a trend toward a decrease in peak GH response to GHRH plus ARG (r = -0.57, P = 0.06) as patient age increased. For cut-off values of 20 microg/liter, the sensitivity of GHRH plus ARG was 75% (95% CI, 57.8-87.9%) and the specificity was 96.4% (95% CI, 89.9-99.2%); whereas, for cut-off values of 24.2 microg/liter, sensitivity was 86.1% (95% CI, 70.5-95.3%), and specificity was 95.2% (95% CI, 88.2-98.7%). The median IGF-I level did not differ between the children with idiopathic pituitary stalk thickness (57 microg/liter; range, 46-68), those with LCH (55 microg/liter; range, 34-63), and those with craniopharyngioma (41 microg/liter; range, 39-49). The present study confirmed the diagnostic potential of the GHRH-plus-ARG test in children with acquired GH deficiency caused by hypothalamic-pituitary lesion. It stimulates GH secretion to a greater extent in those patients with GH deficiency with primary involvement of the hypothalamic area, e.g. patients with idiopathic pituitary stalk thickness or LCH, than in those with both hypothalamic and pituitary lesion, as in craniopharyngioma. In some patients, the GHRH-plus-ARG test stimulates GH response to a so-called: normal value, suggesting that pituitary responsiveness to GHRH plus ARG may fail to recognize acquired GHD. Finally, the number of pituitary hormone deficits and the patient's age affect the GH response to GHRH plus ARG.
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PMID:GHRH plus arginine in the diagnosis of acquired GH deficiency of childhood-onset. 1205 Feb 43

The osteoclast (OC) is a major player in the pathogenic bone destruction of inflammatory bone diseases such as rheumatoid arthritis and Langerhans cell histiocytosis. Recently, it was shown that immature dendritic cells (iDC) fuse faster and more efficiently than monocytes in forming OC-like multinucleated giant cells (MGCs), and that osteopontin (OPN) is involved in the pathogenesis of inflammatory bone diseases. In this study, we hypothesized that OPN is a key factor for generation of OC-like MGCs from iDCs. We used an in vitro culture system to differentiate iDCs, derived from monocytes obtained from the blood of healthy donors, into OC-like MGCs. We evaluated OPN levels and expression of OPN receptors during the course of differentiation. OPN has an arginine-glycine-aspartic acid (RGD) motif, and protease cleavage reveals a SVVYGLR motif. The concentrations of both full-length and cleaved forms of OPN increased during the course of OC-like MGC formation. Expression of OPN RGD- and SVVYGLR-recognizing receptors also increased at later stages. We analyzed whether blocking OPN binding to its receptors affected OC-like MGC formation. Monocytes treated with OPN siRNA were able to differentiate into iDCs effectively; however, differentiation of these iDCs into OC-like MGCs was significantly reduced. The formation of OC-like MGCs was not significantly reduced by RGD synthetic peptide. By contrast, SVVYGLR synthetic peptide caused a significant reduction. These data suggest that the cleaved form of OPN plays a critical role in driving iDC differentiation into OC-like MGCs in the early phase of differentiation, in an autocrine and/or paracrine fashion.
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PMID:Osteopontin has a crucial role in osteoclast-like multinucleated giant cell formation. 2412 63