Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient received intensive radiation to the right renal area for abdominal Hodgkin's disease and approximately ten years later severe hypertension developed. The presence of radiation nephritis with a severely shrunken right kidney was demonstrated and this was accompanied by a substantial increase in renin activity from the right kidney. Treatment with propranolol hydrochloride temporarily lowered the blood pressure and peripheral renin activity levels. Subsequent right nephrectomy resulted in a decrease in renin activity and a reversal of the hypertension. The data implicate a renin angiotensin mechanism as probable cause of hypertension in radiation nephritis.
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PMID:Hypertension in radiation nephritis. Report of a patient with unilateral disease, elevated renin activity levels, and reversal after unilateral nephrectomy. 87 24

Hypertension secondary to stenosis of the left renal artery developed in a thirteen-year-old male six years after completion of inverted Y irradiation (3,600 rad) for abdominal Hodgkin disease. Surgical treatment with nephrectomy resulted in control of the hypertension without the use of antihypertensive agents. We review the literature for this unusual complication of abdominal irradiation, and recommend that a 99mTc-DMSA renal scan, selective renal vein sampling for renin determinations, and renal arteriography be performed on any patient in whom hypertension develops following abdominal irradiation in childhood.
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PMID:Renal artery stenosis and hypertension after abdominal irradiation for Hodgkin disease. Successful treatment with nephrectomy. 686 33

A 14 year old girl with Hodgkin's disease presented with hypertension as an unusual paraneoplastic phenomenon. The elevated plasma renin activity recorded in this patient was possibly a result of Hodgkin's disease. Hypertension as well as plasma renin activity declined to normal values following her successful response to chemotherapy.
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PMID:Hypertension as a paraneoplastic phenomenon in childhood Hodgkin's disease. 826 Sep 4

The local haematopoietic bone marrow (BM) renin-angiotensin system (RAS) mediates pathobiological alterations of haematopoiesis in an autocrine/paracrine/intracrine fashion. Recent data further indicated the existence of angiotensin-converting enzyme (ACE) in human primitive lympho-haematopoietic cells, embryonic, foetal and adult haematopoietic tissues. Human umbilical cord blood cells also express renin, angiotensinogen, and ACE mRNAs. As ACE and other angiotensin peptides function in human haematopoietic stem cells (HSCs) throughout haematopoietic ontogeny and adulthood, local RAS could also have a function in HSC plasticity, and the development of haematological neoplastic disorders. The presence of ACE on leukaemic blast cells within leukaemic BM, on erythroleukaemic cells, ACE-expressing macrophages in lymph nodes of Hodgkin disease, renin activity in leukaemic blasts, angiotensin II as an autocrine growth factor for AML, increased renin gene activity during NUP98-HOXA9 enhanced blast formation, higher levels of BB9/ACE (+) AML isoforms, and altered JAK-STAT pathway as a link between RAS and leukaemia indicated the wide pathobiological aspects of local BM RAS. The comparable biological actions of local RASs throughout the human body (including myocardium, pancreas, pituitary gland, ovary and kidney) represent the true basis for the search of their prominence in tissue functions. Recent data and perspectives of the local BM RAS in health and disease are reviewed in this paper.
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PMID:Pathobiological aspects of the local bone marrow renin-angiotensin system: a review. 2080 97

Interest in applications of protein crystallography to medicine was evident, as the first high-resolution structures emerged in the 50s and 60s. In Cambridge, Max Perutz and John Kendrew sought to understand mutations in sickle cell and other genetic diseases related to hemoglobin, while in Oxford, the group of Dorothy Hodgkin became interested in long-lasting zinc-insulin crystals for treatment of diabetes and later considered insulin redesign, as synthetic insulins became possible. The use of protein crystallography in structure-guided drug discovery emerged as enzyme structures allowed the identification of potential inhibitor-binding sites and optimization of interactions of hits using the structure of the target protein. Early examples of this approach were the use of the structure of renin to design antihypertensives and the structure of HIV protease in design of AIDS antivirals. More recently, use of structure-guided design with fragment-based drug discovery, which reduces the size of screening libraries by decreasing complexity, has improved ligand efficiency in drug design and has been used to progress three oncology drugs through clinical trials to FDA approval. We exemplify current developments in structure-guided target identification and fragment-based lead discovery with efforts to develop new antimicrobials for mycobacterial infections.
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PMID:Structural Biology and the Design of New Therapeutics: From HIV and Cancer to Mycobacterial Infections: A Paper Dedicated to John Kendrew. 2864 15

The development of structure-guided drug discovery is a story of knowledge exchange where new ideas originate from all parts of the research ecosystem. Dorothy Crowfoot Hodgkin obtained insulin from Boots Pure Drug Company in the 1930s and insulin crystallization was optimized in the company Novo in the 1950s, allowing the structure to be determined at Oxford University. The structure of renin was developed in academia, on this occasion in London, in response to a need to develop antihypertensives in pharma. The idea of a dimeric aspartic protease came from an international academic team and was discovered in HIV; it eventually led to new HIV antivirals being developed in industry. Structure-guided fragment-based discovery was developed in large pharma and biotechs, but has been exploited in academia for the development of new inhibitors targeting protein-protein interactions and also antimicrobials to combat mycobacterial infections such as tuberculosis. These observations provide a strong argument against the so-called 'linear model', where ideas flow only in one direction from academic institutions to industry. Structure-guided drug discovery is a story of applications of protein crystallography and knowledge exhange between academia and industry that has led to new drug approvals for cancer and other common medical conditions by the Food and Drug Administration in the USA, as well as hope for the treatment of rare genetic diseases and infectious diseases that are a particular challenge in the developing world.
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PMID:Protein crystallography and drug discovery: recollections of knowledge exchange between academia and industry. 2887 19