Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Correlation of thymic changes with the development of CsA-associated syngeneic graft-versus-host disease (sGVHD) suggested that the development of tolerance depends on the prompt regeneration of the thymus after stopping CsA. Accordingly, we have tested recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor I (rhIGF-1) to determine if they accelerate reconstitution of the rat thymus after CsA-induced involution. After 14 days of CsA, the thymus has marked medullary involution but normally recovers fully in 6 weeks. In this study, LEW rats were injected with vehicle, rhGH, or rhIGF-1 for 21 days after stopping CsA and were examined. The vehicle-treated rats showed partial recovery with respect to Hassall's corpuscles, class II antigen expression, medullary size, medullary dendritic cells (DC), and T cell maturation. The mature thymocytes were predominantly CD8+ T cells. Both rhGH and rhIGF-1 induced significant thymic enlargement compared with the vehicle-treated rats. They also both significantly enhanced regeneration with respect to Hassall's corpuscles. The mature thymocyte population had significantly greater CD4+ cells. In addition, rhIGF-1 induced a significant improvement in the medullary size and medullary DC. While the medullae of a normal thymus are in intimate contact with cortical class II antigen, after CsA the cortex adjacent to the medulla is primarily class II antigen negative. RhGH significantly increased the class II antigen in the deep cortex while rhIGF-1 demonstrated a trend toward greater expression in this region (P = 0.06). We conclude that rhGH and rhIGF-1 accelerate thymic regeneration post-CsA. Further studies are now indicated to establish the potential for these factors to enhance the development of antigen-specific tolerance.
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PMID:Enhancement of thymic recovery after cyclosporine by recombinant human growth hormone and insulin-like growth factor I. 194 74

To evaluate the late-effects of allogeneic bone marrow transplantation (BMT) on endocrine function 20 adults (10 females, 10 males) with hematological malignancies were studied after a mean of 3.2 years (range 1.0-10.0) following BMT. The mean age of patients at the time of BMT was 39 years. Dynamic tests of the hypothalamic-pituitary axis included growth hormone releasing hormone (GHRH), gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) stimulations with measurements of serum growth hormone (GH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH) and prolactin (PRL) responses. Adrenal function was assessed with the adrenocorticotropin (ACTH) test. Five patients (25%) had a subnormal GH response to GHRH stimulation, but all had a normal serum insulin-like growth factor I (IGF-I) value. There was an inverse nonlinear relationship between the body mass index (BMI; kg/m2) and GH response but no relation between the GH response and total body irradiation (TBI), intrathecal treatment or occurrence of graft-versus-host disease. In females, serum FSH and LH basal levels and responses to GnRH, in spite of oestrogen substitution therapy in 9/10 patients, indicated ovarian failure and early menopause. Most responses to GnRH were delayed. All males had elevated serum basal FSH levels indicating damage in seminiferous tubulus and infertility. Serum basal LH was elevated only in four males but testosterone values were all within normal limits. However, the mean free androgen index (FAI) was in the low normal range, and two subjects had abnormally low FAI. Serum free thyroxine (fT4) levels were normal in all but one, but an exaggerated TSH response to TRH occurred in seven patients (35%). Four of them had received TBI and one total nodal irradiation suggesting radiation-induced damage to the thyroid gland. In 19 of the 20 patients, adrenal function judged with ACTH test was normal. We conclude that functional impairments of the hypothalamus-pituitary-gonad/thyroid axis are common while disturbances in GH, adrenal and prolactin occur less often in patients after intensive treatment and BMT. Typically, the target organ is more commonly affected than the hypothalamus-pituitary axis. In spite of normal serum testosterone and LH values, serum FAI may reveal androgen deficiency.
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PMID:Long-term effects of allogeneic bone marrow transplantation (BMT) on pituitary, gonad, thyroid and adrenal function in adults. 972 67