Annals of medicine
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Receptors for many of the cytokines functioning in the haematopoietic system belong to the class I cytokine receptor family. In most cases these receptors share common signal transducing receptor components in the same family, which explains the functional redundancy of haematopoietic cytokines. Interleukin-6 and related cytokines, interleukin-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1, are all pleiotrophic, from the haematopoietic to the nervous system, and exhibit overlapping biological activities. ⋯ In these receptor complexes, gp130 and ligand-specific chains possess no intrinsic tyrosine kinase domain but are associated with cytoplasmic tyrosine kinases. Ligand stimulation triggers homo- or heterodimerization of gp130, leading to activation of the associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews the recent progress in the study of gp130 and the background information from biomedical and biochemical viewpoints.
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The recent identification of mutations in the RET proto-oncogene that are associated with multiple endocrine neoplasia type 2 (MEN 2) syndromes has allowed therapeutic intervention in affected individuals on the basis of direct genetic testing. The principal endocrine neoplasm that occurs in patients with the MEN 2 syndromes is medullary thyroid carcinoma. This thyroid neoplasm is the only consistently malignant feature of the MEN 2 syndromes and it is the most common cause of death in affected patients. ⋯ Those with a positive test can be treated by early thyroidectomy and cured when the disease is microscopic and localized to the thyroid gland. Total thyroidectomy is performed as early as 5 years of age and is associated with minimal morbidity and virtually no mortality. Residual or persistent medullary thyroid carcinoma following thyroidectomy can best be determined by detecting increased levels of calcitonin following the administration of intravenous calcium gluconate and pentagastrin.
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Hyaluronan is a connective tissue polysaccharide which has also been found in blood serum in concentrations < 100 micrograms/L (average 30-40 micrograms/L in middle-aged persons). The serum level is regulated by the influx of the polysaccharide from the tissues via lymph and its receptor-mediated clearance by liver endothelial cells. Markedly high serum levels are noted in certain liver diseases, especially in patients with cirrhosis, when the clearance is impaired. ⋯ Rare hereditary diseases with disturbances of hyaluronan metabolism and elevated blood levels have also been discovered, e.g. Werner's syndrome and cutaneous hyaluronanosis. Information accumulated during the last decade regarding the metabolism of hyaluronan has made this polysaccharide an interesting clinical marker for a number of pathological conditions.
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High-dose chemoradiotherapy (HDCRT) followed by autologous stem cell (ASC) rescue is now widely used in a number of childhood malignancies. The most common to date is neuroblastoma, where it now has an established role as consolidation of initial complete remission in children over the age of 1 year with stage 4 disease. High-dose melphalan alone prolongs progression-free survival, with a small increase in long-term survival. ⋯ It is possible that inherently chemosensitive tumours, such as Wilm's tumour, may be candidates where standard treatment has failed. The replacement of bone marrow reinfusion with cytokine-primed peripheral blood stem cell (PBSC) rescue has reduced the morbidity of these procedures. The issue of the potential risk of reinfusing tumour cells has been addressed in neuroblastoma where purging using immunodepletion or in vitro chemotherapy has been carried out.
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Review Comparative Study
Differences in lipolysis between human subcutaneous and omental adipose tissues.
Hydrolysis of triglycerides to fatty acids and glycerol in fat cells (lipolysis) is of importance for the control of lipid and carbohydrate metabolism. This process is regulated by several hormones and parahormones acting on cyclic AMP formation or breakdown, which in turn influences the activity of hormone sensitive lipase. The latter enzyme stimulates hydrolysis of triglycerides in fat cells. ⋯ The antilipolytic insulin receptors, alpha 2 adrenoceptors and adenosine receptors are most active in the subcutaneous fat cells. In subjects with upper-body obesity the regional variations in the action of catecholamines on lipolysis are further enhanced. Decreased action of beta 2-adrenergic receptors and increased activity of alpha 2-adrenergic adrenoceptors in combination with defects in hormone sensitive lipase function inhibits the lipolytic effect of catecholamines in subcutaneous fat cells whereas increased activity of beta 3-adrenergic receptors and decreased activity of alpha 2 adrenoceptors augment the lipolytic response in visceral fat cells.(ABSTRACT TRUNCATED AT 250 WORDS)