Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leukemia L1210 and P-388 in mice but less active than the previously synthesized, simpler phosphinate derivatives 2 and 3. It appears that the thymidine moiety did not enable these compounds to use the nucleoside transport mechanism of the cells and also failed to increase the selectivity of the 2,2-dimethylaziridine analogues by interference with their binding to cholinesterase. Compound 7 strongly inhibited horse serum cholinesterase, while 6 was inactive.
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PMID:Synthesis of 5'-thymidinyl bis(1-aziridinyl)phosphinates as antineoplastic agents. 727

Essential thrombocythaemia is a myeloproliferative disorder which may transform to acute myeloid leukaemia, especially following therapy with alkylating agents or radioactive phosphorus. We describe the rare occurrence of acute lymphoblastic leukaemia transformation in a patient with known essential thrombocythaemia.
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PMID:Acute lymphoblastic transformation of essential thrombocythaemia. 777 36

A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells.
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PMID:[Hypercalcemia of T-cell leukemia in adults]. 816 27

Two patients with chronic myeloid leukemia (CML) presenting with the hematologic features of essential thrombocythemia (ET) are reported. At diagnosis they showed extremely high platelet counts (4985 and 2800 x 10(9)/l, respectively) and moderate leukocytosis (21 and 17 x 10(9)/l, respectively). In both cases, in addition to the Philadelphia chromosome (Ph), a rearrangement within the major breakpoint cluster region on chromosome 22 was demonstrated, with the breakpoint in the 3' extreme. In patient 1 the disease initially responded to radioactive phosphorus and hydroxyurea, but during the evolutive course a progressive increase in the white blood cell counts was noted, reaching values typical of the chronic phase of CML, and the patient eventually died from blast crisis 45 months after diagnosis. In patient 2, although good control of the platelet counts was achieved with hydroxyurea, the disease also evolved into a blast crisis four months after diagnosis. In both cases monoclonal antibodies and electron microscopy studies demonstrated the megakaryocytic nature of the blast cells. The above features are not consistent with the present and similar cases being Ph-positive ET. Instead, they should be regarded as a special form of CML characterized by a marked protagonism of the megakaryocytic component.
Leukemia 1993 Feb
PMID:Ph-positive chronic myeloid leukemia mimicking essential thrombocythemia and terminating into megakaryoblastic blast crisis: report of two cases with molecular studies. 842 85

After several years of latency, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) cause fatal disease in the cat. The aim of this study was to determine laboratory parameters characteristic of disease progression which would allow a better description of the asymptomatic phase and a better understanding of the pathogenesis of the two infections. Therefore, experimentally infected cats (FIV and/or FeLV positive) and control animals were observed over a period of 6.5 years under identical conditions. Blood samples were analyzed for the following: complete hematology, clinical chemistry, serum protein electrophoresis, and determination of CD4+ and CD8+ lymphocyte subsets. The following hematological and clinical chemistry parameters were markedly changed in the FIV-infected animals from month 9 onwards: glucose, serum protein, gamma globulins, sodium, urea, phosphorus, lipase, cholesterol, and triglyceride. In FeLV infection, the markedly changed parameters were mean corpuscular volume, mean corpuscular hemoglobin, aspartate aminotransferase, and urea. In contrast to reports of field studies, neither FIV-positive nor FeLV-positive animals developed persistent leukopenia, lymphopenia, or neutropenia. A significant decrease was found in the CD4+/CD8+ ratio in FIV-positive and FIV-FeLV-positive animals mainly due to loss of CD4+ lymphocytes. In FeLV-positive cats, both CD4+ and, to a lesser degree, CD8+ lymphocytes were decreased in long-term infection. The changes in FIV infection may reflect subclinical kidney dysfunction, changes in energy and lipid metabolism, and transient activation of the humoral immune response as described for human immunodeficiency virus (HIV) infections. The changes in FeLV infection may also reflect subclinical kidney dysfunction and, in addition, changes in erythrocyte and immune function of the animals. No severe clinical signs were observed in the FIV-positive cats, while FeLV had a severe influence on the life expectancy of persistently positive cats. In conclusion, several parameters of clinical chemistry and hematology were changed in FIV and FeLV infection. Monitoring of these parameters may prove useful for the evaluation of candidate FIV vaccines and antiretroviral drugs in cats. The many parallels between laboratory parameters in FIV and HIV infection further support the importance of FIV as a model for HIV.
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PMID:Parameters of disease progression in long-term experimental feline retrovirus (feline immunodeficiency virus and feline leukemia virus) infections: hematology, clinical chemistry, and lymphocyte subsets. 900 78

With a newly modified analytical method, the concentrations of free and acetylated urinary polyamines were simultaneously determined in a control group (32 cases) and patients with various types of cancers (104 cases, 20 males and 84 females) by gas chromatography-nitrogen-phosphorus detection. Significant concentration differences between normal subjects and various cancer patients were found. The various types of cancers (advanced gastric carcinoma, ovarian cancer, acute myelocyte leukemia, non-Hodgkin's lymphoma) gave unique patterns of urinary polyamine profile as well as significant differences of concentration. To indirectly evaluate the possible involvement of enzymes, precursor-to-product concentration ratios were compared between controls and patients with various types of cancers.
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PMID:Urinary polyamine evaluation for effective diagnosis of various cancers. 906 54

The NIH-07 open-formula nonpurified diet was the selected diet for rodents in the National Toxicology Program's toxicology and carcinogenesis studies from 1980 to 1994. Protein and mineral concentrations of the NIH-07 diet may have increased some diet- and age-associated lesions such as nephropathy. A number of experimental nonpurified diets with lower protein and higher fat and fiber (approximately 15% protein, 7-8.5% fat, and 9-14% crude fiber) than the NIH-07 diet were formulated and evaluated in Fischer 344 (F344) rats. Decreasing protein content of the diet decreased protein consumption by approximately 30% and decreased severity of nephropathy without affecting growth. Increased fat intake seemed to have decreased the incidence or severity of leukemia, a lethal neoplasm of F344 rats. Increasing fiber content without decreasing the caloric density lowered body weight gain and slowed growth of mammary tumors. Higher fat and/or fiber intake decreased the incidences of adrenal pheochromocytomas and medullary hyperplasia in male rats. Nonpurified diets with lower protein and higher fat and fiber concentrations than the NIH-07 diet decreased or delayed diet- and age-associated lesions and increased survivals in 2-y studies. On the basis of these results, a new cereal-based nonpurified diet, designated as NTP-2000, was formulated with approximately 14.5% protein, approximately 8.2% fat, approximately 9.3% fiber and a calcium:phosphorus molar ratio of approximately 1.3. The NTP-2000 diet was compared with the NIH-07 diet in a 13-wk study in F344 rats. The NTP-2000 diet was adequate for growth, did not affect the hematological parameters and did not cause substantial changes in blood chemistry, serum enzyme or serum electrolyte values. The NTP-2000 diet decreased liver and kidney weights, prevented nephrocalcinosis and decreased the severity of diet- and possibly age-associated lesions.
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PMID:New nonpurified diet (NTP-2000) for rodents in the National Toxicology Program's toxicology and carcinogenesis studies. 916 50

Forty-one patients with polycythemia vera (PV) according to the PVSG criteria were analysed retrospectively from January 1960 to March 1996. There were 23 male and 18 female patients with a median follow-up of 66.5 months (3-431 months). Median age was 62 (range: 37-85). The median hemoglobin level at diagnosis was 18.8 g/dl. Four patients were treated by venesection alone, 20 patients received hydroxyurea and intermittent venesection, 3 were treated with radioactive phosphorus alone, and 14 had both hydroxyurea and radioactive phosphorus. During the course of illness, 14 patients (34%) developed a total of 19 thrombotic events. Of the thrombotic events, 16 were arterial and 3 were venous. Two patients had both arterial and venous thrombosis sequentially. The probability of thrombosis-free survival after treatment was 83% at 10 years and 73% at 20 years. One patient developed post-polycythemic myeloid metaplasia 24 months after diagnosis. Of 17 patients exposed to radioactive phosphorus, only 1 developed secondary acute myeloid leukemia (AML) 9 years afterwards. Of the 20 patients treated with hydroxyurea for a median duration of 63.5 months (2-130 months), there is no case of secondary malignancy. Overall survival was 83% at 10 years and 62% at 20 years. In conclusion, PV in Chinese is a relatively benign disease with a low risk of thrombosis as compared to Caucasian patients. Hydroxyurea has a very low risk of secondary leukemia and is a safe drug to use in Chinese patients with PV.
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PMID:Polycythemia vera in Chinese patients: thirty-six years of experience. 929 70

We describe a method for the profiling of polyamines, N-acetylated polyamines and the polyamine analogues N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) in L1210 murine leukaemia cells by capillary gas chromatography with nitrogen-phosphorus detection. The method makes use of four intemal standards. Prepurification comprises deproteinization, isolation with Sep-Pak silica at pH 9.0, conversion to heptafluorobutyryl derivatives and postderivatization organic fluid extraction. Within- and between-series precisions (given as CV.s) for analysis of 1-2x10(6) cells were: putrescine 5.5 and 29.4%; spermidine 1.6 and 7.1%; and spermine 3.2 and 7.6%, respectively. Recoveries relative to the respective internal standards, were in the 70.6-104.7% range. Accuracy and precision of measurements of BE-4-4-4-4 can probably be improved by the introduction of a separate pentamine internal standard. We conclude that the method can be used for studying the effect of BE-3-3-3 and BE-4-4-4-4, and possibly their metabolites, on polyamine homeostasis (biosynthesis, retroconversion, transport, terminal catabolism) and polyamine function.
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PMID:Simultaneous determination of polyamines, N-acetylated polyamines and the polyamine analogues BE-3-3-3 and BE-4-4-4-4 by capillary gas chromatography with nitrogen-phosphorus detection. 939 Jul 11

Eleven urinary polyamine levels were determined in controls (32 cases) and 43 patients with varying stages of leukemia including initial, relapse and complete remission, using gas chromatography nitrogen-phosphorus detection. Also, to indirectly evaluate the possible involvement of enzymes, precursor to product concentration ratios were compared between controls and patients with each stage of leukemia. As a result, it is confirmed that the ratio of N1-acSpd/N8-acSpd could be used as a diagnostic marker and the level of N1,N12-diacetylspermine could be used for determining disease stage and as a malignancy marker for leukemia. An altered metabolic pathway related to leukemia is also proposed in which N1,N12-diacetylspermine can be produced directly from spermine and N1,N12-diacetylspermine is a major source of N1-acetylspermidine.
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PMID:Polyamine profiles in the urine of patients with leukemia. 946 84


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