Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the case of a 10-year-old boy with molecular relapse of CML following unrelated donor BMT who developed fatal grade 4 acute GVHD of the gut and liver following one antigen-mismatched donor lymphocyte infusion. Previous experience of donor lymphocyte infusion in the HLA-mismatched setting is reviewed and the role of adoptive immunotherapy in this situation is discussed.
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PMID:Fatal graft-versus-host disease following HLA-mismatched donor lymphocyte infusion. 1160 79

The family planning program is not restricted to population control; it also aims at the wider aspect of family welfare and human health. A large number of human diseases are due to genetic abnormalities. Examples are mongolism (Down's syndrome), ovarian dysgenesis (Turner's syndrome), nonfunctional testes (Klinefelter's syndrome), chronic myeloid leukemia, anemia, thalassemia, congenital malformations, and schizophrenia. Mental defects include imbeciles and the feebleminded. Constitutional diseases include diabetes, idiopathic epilepsy, pernicious anemia, and some thyroid abnormalities. Some chronic diseases also have a significant genetic component in their etiology, such as asthma and other allergies. About half of the stillbirths and embryonic wastage are suspected of being due to genetic malformations. Consanguinity has an important bearing on malformations and developmental anomalies. In India, where consanguinity is more frequent, malformations per 1000 births were 8.6 and 3.1 in 2 centers studied. Neural tube defects, harelip, cleft palate, and malformations of the gut and of limbs were prevalent. The population that needs genetic counseling is not large. Persons suffering from hereditary dise ases having a high risk of transmission should be advised to refrain fro m having children. A correct diagnosis, complete family history, and kn owledge of the literature on inherited disease is needed by the counselo rs. Family planning programs should include genetic counseling.
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PMID:Genetic counselling in family planning. 1225 20

YNK01 (Starasid) is a prodrug that is adsorbed in the gut and is transformed in the liver in arabinosyl cytosine (AC). Low-dose AC (LDAC) is useful for the treatment of Philadelphia positive (Ph+) chronic myeloid leukemia (CML), especially in combination with alpha-interferon (alphaIFN). The use of YNK01 can avoid the daily s.c. injection of conventional AC. To assess the safety and the efficacy of alphaIFN and YNK01, we enrolled 86 consecutive previously untreated chronic phase Ph+ CML patients in a phase II study of alphaIFN (Intron-A) 5 MIU/m(2) daily and YNK01 600 mg daily 14 days a month. The 6-month complete hematologic response and the 12-month major cytogenetic response rates were 78 and 28%, respectively. In a prior study of alphaIFN and conventional LDAC, they were 62 and 22%, respectively. However, the compliance to the treatment was poor, with 25% of cases discontinuing the treatment within the first year. This was not because of the severity of the side effects but because of the frequency, duration and repetition of the side effects, for an overall frequency of 13.17 adverse events, mostly grade 1 and 2, per patient per year. Therefore, the study of this effective combination is being pursued, testing lower doses of alphaIFN and YNK01.
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PMID:A phase II study of alpha-interferon and oral arabinosyl cytosine (YNK01) in chronic myeloid leukemia. 1264 44

A 35-year-old male with chronic myeloid leukemia in the accelerated phase received a peripheral blood stem cell transplant from his HLA-DR-mismatched mother. Graft-versus-host disease (GVHD) prophylaxis was with short-term methotrexate and tacrolimus. After transplantation, grade II skin acute GVHD occurred and was unsuccessfully treated with bolus methylprednisolone administration. The acute GVHD progressed to grade III of the skin, gut and liver, and mycophenolate mofetil (MMF) was accordingly administered at a daily dose of 2 g. This treatment resulted in a dramatic improvement in the clinical features of the acute GVHD. The patient suffered from hemorrhagic cystitis and several episodes of cytomegalovirus antigenemia. MMF may be useful for steroid-resistant acute GVHD despite an increasing risk of viral infections.
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PMID:[Successful treatment of refractory acute GVHD with mycophenolate mofetil after peripheral blood stem cell transplantation from the patient's one locus-mismatched mother]. 1457 20

The reported incidence of grades II to IV acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation with HLA-identical sibling donors has increased considerably during the past 15 to 20 years at our center. The purpose of this study was to evaluate the potential reasons for this change. We reviewed organ stages and overall grades of GVHD for 2220 patients who received a first marrow or peripheral blood cell transplant from an HLA-identical sibling or an HLA-allele-matched unrelated donor with the use of a posttransplantation immunosuppressive regimen that included both methotrexate and cyclosporine between 1985 and 2001. The most striking change was an increased incidence of stage 1 gut involvement from 10% to 20% before 1992 to 50% to 60% since 1992, both with related and unrelated donors. This change increased the incidence of grade II GVHD with sibling donors, such that the overall incidence of grade II to IV GVHD is now 60% to 70%. Among patients with chronic myeloid leukemia in chronic phase, the increasingly frequent diagnosis of acute GVHD since 1992 has not been associated with decreased survival. A high diagnostic sensitivity and increased awareness that gut GVHD can occur without skin involvement account for the increased incidence of acute GVHD at our center.
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PMID:Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. 1511 31

Graft-versus-host disease and disease relapse are the 2 major causes of failure of allogeneic hematopoietic stem cell transplantation (SCT). Ideally, patients who undergo transplantation for malignancies would receive the minimum effective acute graft-versus-host disease (GVHD) prophylaxis to maximize the graft-versus-tumor potential of the allogeneic SCT. Tailoring acute GVHD prophylaxis to the risk for each patient has long been a goal for SCT, but no practical way to adjust acute GVHD prophylaxis has been developed. In murine models of acute GVHD, gut damage from the preparative regimen resulting in the release of many mediators is crucial for initiation of acute GVHD. Using diarrhea as a marker of gut damage, we performed a retrospective study of patients at the Johns Hopkins Hospital given matched sibling transplants for chronic myelogenous leukemia to determine whether gut damage during the preparative regimen is predictive of the development of acute GVHD in humans. Logistic regression models were used to perform the retrospective analysis of the relation of diarrhea during the preparative regimen to a significant acute GVHD grade. This work demonstrated a significant positive correlation between the sum of diarrhea on days 4 to 7 after SCT and acute GVHD and showed a borderline significant positive correlation between the sum of diarrhea on days 1 to 3 and acute GVHD. This is the first correlation demonstrated between gut damage during the preparative regimen and acute GVHD severity in humans. This suggests that damage from the preparative regimen could be used as a marker for the risk of acute GVHD. Prospective trials would have to test whether acute GVHD prophylaxis could be adjusted according to this risk. This may result in a greater graft-versus-tumor effect for patients with less risk of acute GVHD.
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PMID:Gastrointestinal toxicity from the preparative regimen is associated with an increased risk of graft-versus-host disease. 1568 70

Oxidative and carbonyl stress leads to generation of N(epsilon)-carboxymethyllysine-modified proteins (CML-mps), which are known to bind the receptor for advanced glycation end products (RAGE) and induce nuclear factor (NF)-kappaB-dependent proinflammatory gene expression. To determine the impact of CML-mps in vivo, RAGE-dependent sustained NF-kappaB activation was studied in resection gut specimens from patients with inflammatory bowel disease. Inflamed gut biopsy tissue demonstrated a significant up-regulation of RAGE and increased NF-kappaB activation. Protein extracts from the inflamed zones, but not from noninflamed resection borders, caused perpetuated NF-kappaB activation in cultured endothelial cells, which was mediated by CML-mps including CML-modified S100 proteins. The resulting NF-kappaB activation, lasting 5 days, was primarily inhibited by either depletion of CML-mps or by the addition of sRAGE, p44/42 and p38 MAPKinase-specific inhibitors. Consistently, CML-mps isolated from inflamed gut areas and rectally applied into mice caused NF-kappaB activation, increased proinflammatory gene expression, and histologically detectable inflammation in wild-type mice, but not in RAGE-/- mice. A comparable up-regulation of NF-kappaB and inflammation on rectal application of CML-mps was observed in IL-10-/- mice. Thus, CML-mps generated in inflammatory lesions have the capacity to elicit a RAGE-dependent intestinal inflammatory response.
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PMID:Posttranslationally modified proteins as mediators of sustained intestinal inflammation. 1700 81

Glycation is a nonenzymatic condensation reaction between reducing sugars and amino groups of proteins that undergo rearrangements to stable ketoamines, leading to the formation of advanced glycation end products (AGEs) including fluorescent (argpyrimidine) and nonfluorescent (N(epsilon)-carboxymethyllysine; CML) protein adducts and protein cross-links. AGEs are formed via protein glycation and correlate with processes resulting in aging and diabetes complications. Reactive carbonyl species such as glyoxal and methylglyoxal are ubiquitous by-products of cell metabolism that potently induce the formation of AGEs by nonenzymatic protein glycation and may achieve plasma concentrations of 0.3-1.5 micromol/L. In this in vitro study histone H1 glycation by glyoxal, methylglyoxal, or ADP-ribose was used to model nonoxidative protein glycation, permitting us to distinguish specific AGE inhibition from general antioxidant action. Rutin derivatives were tested as AGE inhibitors because rutin, a common dietary flavonoid that is consumed in fruits, vegetables, and plant-derived beverages, is metabolized by gut microflora to a range of phenolic compounds that are devoid of significant antioxidant activity and achieve blood concentrations in the mumol/L range. Our data show that in a 1:1 stoichiometry with glyoxal or methylglyoxal, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3,4-dihydroxytoluene (DHT) are powerful inhibitors of CML and argpyrimidine histone H1 adduct formation, respectively. Furthermore, when DHPAA and DHT were tested as inhibitors of histone H1 glycation by the powerful glycating agent ADP-ribose, they inhibited glycation as effectively as aminoguanidine. These results suggest that dietary flavonoids may serve as effective AGE inhibitors and suggest mechanisms whereby fruit- and vegetable-rich diets contribute to the prevention of processes resulting in aging and diabetes complications.
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PMID:Rutin metabolites: novel inhibitors of nonoxidative advanced glycation end products. 1996 69

Honey is an established traditional medicine with a variety of putative nutritional and health effects, including antibacterial, antioxidant, anti-inflammatory and prebiotic. The aim of the present study was to investigate the safety of consuming manuka honey, UMF 20+, on healthy individuals by establishing whether UMF 20+caused an allergic response (as measured by IgE levels), changed major commensal and beneficial microbial groups in the gut and/or affected levels of one of the most common advanced glycation endpoints, N-(carboxymethyl)-lysine (CML). The study had a randomised, double-blind cross-over design. A total of twenty healthy individuals aged 42-64 years were recruited. We tested two different honeys- a multiflora honey and UMF 20+, both produced by Comvita New Zealand Ltd (Te Puke, New Zealand). Multiflora honey or UMF 20+(20 g) was consumed daily for 4 weeks, with a 2-week 'washout' period in between. Blood samples were collected every week for each intervention period and used to measure total IgE levels in serum and advanced glycation endproducts - a consequence of methyglyoxal accumulation. Faecal samples were collected at the beginning and end of each 4-week period. DNA was extracted from faecal samples and the levels of a number of microbial groups in the gut, both beneficial and commensal, were analysed. Neither product changed the levels of IgE or CML or altered gut microbial profiles during the trial, confirming that UMF 20+is safe for healthy individuals to consume. Despite anecdotal evidence suggesting that manuka honey is good for digestive health, we observed no beneficial effects on lower gut bacterial levels with either honey in this healthy population.
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PMID:Demonstrating the safety of manuka honey UMF 20+in a human clinical trial with healthy individuals. 2006 84

All India Institute of Medical Sciences is an Apex Institute and caters more than 1.5 million out-patients and 80,000 in-patients every year. In this study, they have presented interesting results of patients treated with interferon, interferon plus cytarabine and then with imatinib plus cytarabine. They have presented data of 525 patients treated on imatinib alone. Imatinib dose was increased in 56 (10.6%) patients and regain of complete hematological response was seen in 26 patients. A total of 14 patients were transplanted for different indications of chronic myeloid leukemia and out of which 12 patients are doing well, while two died due to Grade IV gut graft-versus-host disease.
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PMID:Report of chronic myeloid leukemia in chronic phase from All India Institute of Medical Sciences, 1990-2010. 2451 98


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