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

Bone marrow transplants are being increasingly used to treat a broadening spectrum of serious pediatric conditions including hematologic, metabolic, and immune disorders. A common adverse effect is slowing of statural growth which, according to the author's experience, reaches 0.4 SD a year on average in the highest risk group with progressive graft-versus-host disease after whole body irradiation and transplantation of an allograft. Growth was normal in autograft recipients treated by moderate-intensity chemotherapy. High-dose chemotherapy, in particular with busulfan and cyclophosphamide, has been reported to cause growth retardation. The mechanism of failure to gain height is complex. Partial growth hormone deficiency is rare. Relative resistance of growth plates is the most likely mechanism. The role and efficacy of growth hormone replacement therapy is unclear. Conditioning regimens can affect ovarian and testicular function. Peripheral thyroid resistance can occur after whole body irradiation and transplantation of an allograft. The high rate of growth and endocrine disorders warrants close monitoring including full evaluations of growth and pubertal development as well as periodic endocrinologic investigations.
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PMID:[Endocrinal sequela in bone marrow transplantations during childhood and adolescence]. 823 98

Long-term sequelae of bone marrow transplantation (BMT) are a major concern among long-term survivors since the procedure has been considerably developed over the past decade. In this study, linear growth and growth hormone (GH) secretion were evaluated in 25 children (14 males and 11 females) with various neoplastic or non-neoplastic hematological disorders who had survived for more than 3 years after BMT. Impaired linear growth after BMT, as defined by a change in height standard deviation score (SDS) by more than -1.0 SD, was observed in 14 patients (56%). Four children showed severe growth suppression with a decrease in SD score by more than 2.0, and 10 exhibited a moderate reduction by between 1.0 and 2.0 SD. A recovery of normal height velocity was observed in those who had received BMT at a younger age. The type of disease, a difference in preconditioning regimen, the presence of chronic graft-versus-host disease or a GH secretory capacity 1 year after BMT were not contributing factors for impaired growth. A serial examination of GH secretion with insulin-induced hypoglycemia demonstrated that poor GH secretion was not necessarily a prerequisite for impaired growth. These results indicate that the secretory status of GH does not predict the future growth pattern of children who received BMT.
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PMID:Growth and growth hormone secretion in children after bone marrow transplantation. 846 May 40

An autopsy case of transfusion-associated graft-versus-host disease (TA-GVHD) is reported with immunohistochemical investigation and polymerase chain reaction (PCR) analysis. In a 58-year-old male, esophagectomy for carcinoma was performed with a transfusion of 4 units of fresh whole blood. Diarrhea, fever, erythematous rash, pain and leukopenia occurred with an onset 11 days after the operation. He died of sudden dyspnea 29 days after the operation. At autopsy, histological examinations revealed lichenoid lesion in the skin, injury of mucosal epithelia in the digestive tract and damage of interlobular bile ducts in the liver. Immunohistochemical investigation suggested the association between these lesions and CD8-positive T lymphocytes. Severe disturbances of bone marrow and lymphoid organs were accompanied with gram-positive cocci infection in the lungs, esophagus and small intestine. PCR analysis of DNA at microsatellite loci, human growth hormone (HGH) and apolipoprotein B (Apo B), showed DNA chimerism and established the definitive diagnosis of TA-GVHD.
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PMID:Transfusion-associated graft-versus-host disease diagnosed by polymerase chain reaction analysis of DNA microsatellites: an autopsy case with immunohistochemical investigation. 894 30

The exact contribution of growth hormone (GH) deficiency to the adverse growth outcome, in those receiving cranial irradiation (18-24 Gy) or total-body irradiation for haematological malignancies in childhood, remains difficult to disentangle as nearly always the cause of the growth disturbance is multifactorial: chemotherapy, graft-versus-host disease, hypothyroidism, and skeletal dysplasia may all impact on growth. There are few published data from which one can assess the efficacy of GH replacement on final height in those children who received cranial irradiation (18-24 Gy) and/or total-body irradiation; there is no evidence, however, of an increased risk of leukaemic relapse. Endocrine reassessment in the teenagers, who received cranial irradiation (18-24 Gy) for acute lymphoblastic leukaemia many years earlier, revealed a significant incidence of GH deficiency with the additional suggestion that many had been GH deficient for several years. This raises a number of important questions: What is the best way to organize long-term endocrine follow-up? How often should GH status be reassessed? What are the specific benefits of GH replacement in adult life for such individuals? These and other questions require further study.
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PMID:Growth and growth hormone status following treatment for childhood leukaemia. 969 Dec 6

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

Few data are available on the long-term effect of bone marrow transplantation (BMT) on growth. This study examines those factors that play a role in the final height outcome of patients who underwent BMT during childhood. Data on 181 of 230 patients with aplastic anemia, leukemias, and lymphomas who had BMT before puberty (mean age, 9.8 +/- 2.6 years) and who had reached their final height were analyzed. An overall decrease in final height standard deviation score (SDS) value was found compared with the height at BMT (P < 10(7)) and with the genetic height (P < 10(7)). Girls did better than boys, and the younger in age the person was at time of BMT, the greater the loss in height. Previous cranial irradiation + single-dose total body irradiation (TBI) caused the greatest negative effect on final height achievement (P < 10(4)). Fractionation of TBI reduces this effect significantly and conditioning with busulfan and cyclophosphamide seems to eliminate it. The type of transplantation, graft-versus-host disease, growth hormone, or steroid treatment did not influence final height. Irradiation, male gender and young age at BMT were found to be major factors for long-term height loss. Nevertheless, the majority of patients (140/181) have reached adult height within the normal range of the general population.
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PMID:Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the Working Party for Late Effects-EBMT. 1036 Nov 7

Late effects following HSCT are related to either the transplant process or to the transplant preparative regimen. Problems related to the transplant process include delayed recovery of the immune system and chronic GVHD. Chronic GVHD presents between 3-14 months post-HSCT in approximately 20% of matched sibling transplants and 40% of matched unrelated donor recipients. Most commonly involved sites are skin, mouth, liver, gastrointestinal tract, and eye. Patients with platelet count < 100,000/ml and receiving cortocosteroid therapy at day 80 with any clinical manifestations of chronic GVHD require prolonged immune suppressive therapy with prednisone, cyclosporine +/- other agents. Treatment should be administered until all clinical and pathological signs and symptoms of chronic GVHD have resolved which may take one to several years. Problems related to the transplant preparative regimen include those involving the endocrine system, eyes, lungs, bone, and development of secondary malignancies. Endocrine deficiencies include growth failure with growth hormone (GH) deficiency, overt hypothyroidism, primary gonadal failure, Type 1 or Type 2 diabetes, and exocrine pancreatic insufficiency. These problems develop at any time post-HSCT, but usually occur within the first few years and should be treated with appropriate hormone supplementation. Eye problems are primarily related to development of cateracts secondary to total body irradiation (TBI) or prolonged corticosteroid use. Cateracts developing after fractionated frequently do not require removal. Pulmonary problems may be due to bronchiolitis obliterans (BO) or to restrictive lung disease. BO may be associated with chronic GVHD and may respond to chronic GVHD therapy. Restrictive lung disease does not occur for many years after HSCT. There is not therapy for this problem. Development of decreased bone mineral density (BMD) is related to GH deficiency and/or corticosteroid therapy. Treatment includes withdrawal of corticosteroids, administration of GH and calcium, Vitamin D and antiresorptive agents. All malignant disease survivors are at risk for development of secondary malignancies, including survivors of HSCT. Recipients of TBI are at highest risk as are children. All pediatric and adult survivors of HSCT should be followed for their life-time for development of delayed effects of transplantation.
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PMID:Chronic graft-versus-host disease and late effects after hematopoietic stem cell transplantation. 1243 Aug 95

The aim of hematopoietic stem cell transplantation (HSCT) is to cure patients of malignancies, autoimmune diseases, and immunodeficiency disorders by redirecting the immune system: the often described graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Unfortunately, fulfillment of this goal is often hampered by relapse of the underlying disease, graft-versus-host disease (GVHD), or severe opportunistic infections, which account for the majority of post-transplantation deaths. Moreover, studies of long-term survivors of transplantation indicate an accelerated immune aging due to the transplantation procedure itself, preceding chemo- or radiotherapy, and acute and chronic GVHD. Significant advances have been made towards overcoming these obstacles by enhancing immune reconstitution with hematopoietic growth factors (HGFs) such as granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) or through the application of cytokines. In addition, there are approaches to promote the thymic-dependent development of naive T cells, which are prepared for the interaction with a multitude of pathogens. Examples are the application of keratinocyte growth factor (KGF), neuroendocrine hormones such as growth hormone or prolactin, sex hormone ablation, or the invention of a three-dimensional artificial thymus based on a cytomatrix. Might these measures result in a higher rate of healthy and fully recovered patients? Here we review progress in each of these areas.
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PMID:Hematopoietic growth factors including keratinocyte growth factor in allogeneic and autologous stem cell transplantation. 1763 Nov 84

Hematopoietic stem cell transplantation (HSCT) is associated with a period of immune incompetence that particularly affects the T cell lineage. Strategies to enhance T cell reconstitution could significantly improve the survival of HSCT recipients by decreasing the incidence of fatal infectious complications and by enhancing graft-versus-tumor activity. In recent years, a variety of promising strategies have been established in preclinical models to improve T cell recovery in particular after allogeneic T cell-depleted HSCT, without aggravating graft-versus-host disease while preserving or even improving graft-versus-tumor activity. These therapies include treatment with keratinocyte growth factor (KGF), growth hormone (GH), LHRH agonists, interleukin 7 (IL-7) and interleukin 15 (IL-15). Thanks to the establishment of Notch-based culture systems, adoptive cellular therapies with T lineage-committed precursor cells have become feasible, since early T cell progenitors can now easily be generated in vitro in large quantities and have been proven to be very effective in enhancing T cell reconstitution and anti-tumor activity after allogeneic T cell-depleted HSCT. The translation of most of these strategies into clinical trials is likely and in some cases Phase I/II studies are already underway.
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PMID:Enhancing T cell reconstitution after hematopoietic stem cell transplantation: a brief update of the latest trends. 1790 11


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