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)

Ninety-seven patients with light chain disease (LCD) were studied. The median survival from diagnosis was 30 mo for 52 patients with kappa-LCD and 10 mo for 45 patients with lambda-LCD (p less than 0.0007). A lower proportion of kappa-LCD patients (15.7%) than lambda-LCD patients (42.2%) died within the first 6 mo after diagnosis. The survival of the remaining patients with kappa-LCD was still much longer than of those with lambda-LCD (p = 0.022). The shorter survival of lambda-LCD patients could not be ascribed to an increased incidence of recognized manifestations indicating a poor prognosis (e.g., anemia, hypercalcemia, azotemia, low albumin, the extent of osteolytic lesions, or proteinuria), the incidence of amyloidosis, the clinical stage of the disease at diagnosis, or the response to treatment, and remains unexplained. A comparison of the clinical manifestations of LCD with those of other myelomas revealed some differences. LCD patients were slightly younger than IgA and IgG patients but older than IgD patients. A 1:1 ratio of males to females was similar to the ratios in IgA and IgG myeloma, but differed from the 3:1 ratio reported for IgD myeloma. Plasma-cell leukemia developed in 7/97 LCD patients, an incidence that was higher than has been reported in other myelomas. The initial BUN was more than or equal to 30 mg/100 ml in 54 of 95 LCD patients, an incidence that was higher than has been reported for IgA and IgG myeloma, but lower than the incidence in IgD myeloma. The incidence of amyloidosis in LCD (23 of 97 patients) was similar to that reported for IgA and IgG myeloma, but less than the incidence in IgD myeloma.
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PMID:Kappa and lambda light chain disease: survival rates and clinical manifestations. 82 Mar 87

The presence of the human T-cell leukemia virus (HTLV) in Dominican blood donors and patients with tropical spastic paraparesis (TSP) was first detected in 1987. To define further the seroprevalence in the country, nearly 4,000 samples from high- and low-risk populations, as well as patients with neurological disease and with leukemia or lymphoma were tested for HTLV antibodies. A 1-2% seropositivity rate was found among the low-risk population, a 2-5% in the high-risk, and at least 87% in those with TSP. A few patients with malignancy also had antibodies to HTLV. An increase in seropositivity with age and a predominance of female seropositive individuals were found. Infectious virus was isolated from TSP patients, prostitutes, and family members of index patients. These data indicate the substantial level of HTLV infection in another Caribbean country and its relation to neurologic disease.
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PMID:Prevalence of HTLV infection in the Dominican Republic: association with neurological disease. 134 26

In a prospective study the incidence of allo-immunization and platelet refractoriness was investigated using a consequently leucocyte-poor blood product regime. Twenty-five previously non-transfused patients with acute leukaemia (11 men, 7 women) or autologous bone marrow transplantation for Hodgkin's or non-Hodgkin's lymphoma (2 men, 5 women) received at least 80 donor units of filtered red cells (filtration within 24 h after donation, leucocyte content 8.5 +/- 3.9 x 10(6)/U) and/or of platelet concentrate (produced by the buffy coat method, leucocyte content: 7.8 +/- 4.2 x 10(6)/U). A 1-hour recovery of 20% in three consecutive transfusions, in the absence of clinical factors known to impair increment, was defined as platelet refractoriness. HLA class I antibody screening with a panel of 60 cells was performed before the first transfusion and after 80 U of blood components. Of 25 patients who entered this study, 6 patients developed platelet refractoriness after a mean of 38 units of blood components (range 26-45 U); all 6 were female with a history of multiple pregnancies. In 19 patients regarded as non-refractory, no HLA antibodies were demonstrated (13 men, 6 women). This study, though limited in size, suggests that the use of blood products containing less than 1 x 10(7) leucocytes/donor unit prevents primary HLA class I immunization and platelet refractoriness.
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PMID:Prevention of primary HLA class I allo-immunization with leucocyte-poor blood components produced without the use of platelet filters. 148 73

Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) and the lymphokine interleukin-4 (IL-4) induces expression of germ line immunoglobulin C epsilon transcripts and class switching to the C epsilon gene. We show that LPS-plus-IL-4 induction of germ line epsilon transcripts (termed I epsilon transcripts) occurs at the transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region of DNA surrounding the I epsilon promoter endows inducible transcription to a heterologous reporter gene stably transfected into these cells; such inducible expression depends on combined treatment with LPS and IL-4. Analyses of constructs transiently introduced into a B-cell lymphoma line demonstrated that LPS-plus-IL-4-inducible expression can be conferred by a 179-bp segment of DNA spanning the I epsilon transcriptional initiation site. Mutational analyses demonstrated that this expression depended on DNA sequences within a conserved region directly upstream from the I epsilon transcriptional initiation region. One nuclear protein that is constitutively expressed in normal B cells binds to the downstream end of the conserved sequence; its binding specificity correlates with the functional effect of several mutations. Two additional proteins, which are induced by IL-4 treatment of splenic B cells, bind to the transcription initiation sites of I epsilon. These proteins are indistinguishable in binding assays from proteins previously shown to bind an enhancer region of the class II major histocompatibility complex gene A alpha.
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PMID:Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts. 192 63

The human T-cell leukemia virus type I (HTLV-I) is transmitted via breast milk, semen, or blood transfusion. The last route was not responsible for HTLV-I infection before the advent of modern medicine, nor will it be a major route in the future because anti HTLV-I antibody-positive blood is now screened out. Thus, the carriage rates in various areas of Japan have to be explained by the former two transmission methods. Based on the relationship between the two modes of transmission and carriage rates, several simulation experiments were performed. These experiments revealed that: (a) No population with a vertical transmission rate lower than 50% can be maintained as endemic for the virus. (b) Slight differences in horizontal transmission rates can cause a large change of the carriage rates. (c) A 1,000-fold carriage rate difference would become indistinguishable within a hundred generations if both modes of transmission were operating at nearly the same rate. (d) The probability of a formerly non-endemic population becoming endemic due to a single female carrier is not negligible. (e) Prevention of vertical transmission is much more effective in lessening the carriage rate within a short period of time than is prevention of horizontal transmission. A simulation for a real population is also presented.
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PMID:Simulation of dynamic changes of human T-cell leukemia virus type I carriage rates. 210 43

A 3.0-kilobase-pair Epstein-Barr virus (EBV) DNA segment necessary for lymphocyte immortalization encodes at least part of a nuclear protein (EBNA2) which is characteristically expressed in latently infected, immortalized cells. A 1.5-kilobase open reading frame within this DNA segment has now been inserted into a murine leukemia virus (MuLV)-derived expression vector (pZIP-NEO-SV(X)1) which provides for transcription of heterologous DNA but not for translational start. Transfection of the recombinant DNA into NIH 3T3 cells resulted in expression of a full-sized EBNA2 which localized to the cell nucleus. Significant new evidence is thereby provided that this 1.5 kilobase open reading frame includes a translational start site and encodes the entire EBNA2 protein. Transfection of the recombinant DNA into a helper cell line (psi am22b) providing amphotropic MuLV-packaging functions resulted in the release of a recombinant MuLV carrying the EBNA2 gene. This recombinant virus can infect rodent cells and convert them to stable EBNA2 expression. Rat-1 cells infected with the MuLV EBNA2 recombinant expressed EBNA2 and grew more rapidly in medium supplemented with 1 or 0.5% fetal calf serum than did Rat-1 cells infected with MuLV vector lacking EBNA2. The Rat-1 cells expressing EBNA2 remained contact inhibited, anchorage dependent, and nontumorigenic in nude mice. Different EBV isolates have one of at least two EBNA2 alleles. Despite divergence between the two alleles, a human serum recognized the prototype EBNA2 allele (EBNA2A) as well as the variant EBNA2B allele characteristic of some Burkitt tumor EBV isolates. The EBNA2B allele was also expressed from the MuLV-derived vector. The reproducible expression of EBNA2A or EBNA2B from these recombinant vectors will facilitate analysis of the EBNA2A and EBNA2B phenotypes.
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PMID:Expression of the Epstein-Barr virus nuclear protein 2 in rodent cells. 242 68

In platelets, agonists that stimulate phosphoinositide turnover cause the rapid phosphorylation of a protein of apparent relative molecular mass (Mr) 40-47,000, called P47, by protein kinase C (PKC). Diverse identities have been ascribed to P47 including lipocortin, inositol 1,4,5-trisphosphate 5-phosphomonoesterase, pyruvate dehydrogenase alpha subunit and an actin regulatory protein. We have isolated human P47 clones by immunological screening of a lambda gt11 complementary DNA library from HL-60 cells, a human promyelocytic leukaemia cell line. P47 recombinants thus identified hybridized to a 3.0 kilobase (kb) messenger RNA in mature white blood cell lines; the same mRNA was induced in HL-60 cells during differentiation. A 1,050 base pair (bp) open reading frame that could encode a protein of Mr40,087 was confirmed by comparison with peptide sequences from platelet P47, and by expression of the putative recombinant P47 in E. coli and in vitro. The P47 sequence appears to have been conserved throughout vertebrate evolution, and is not similar to any other known sequence including human lipocortin and the alpha subunit of pyruvate dehydrogenase. The P47 protein contains a potential Ca2+-binding 'EF-hand' structure and a region that strongly resembles known PKC phosphorylation sites.
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PMID:Molecular cloning and expression of the major protein kinase C substrate of platelets. 289 30

The inactivation of the enzyme glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was studied in exponentially growing murine leukemia cells. A 1-hr incubation with 1.6 +/- 0.2 microM BCNU resulted in a 50% inhibition of glutathione reductase, while 10 microM BCNU caused total inhibition of the enzyme. The time required for 50% inhibition of glutathione reductase by 10 microM BCNU was 7 min. The recovery of glutathione reductase activity was studied by incubating cells with 10 microM BCNU for 30 min to inhibit all glutathione reductase activity, washing the cells free of drug, and continuing the incubation in fresh medium. Fifty percent of the activity returned within 12 hr. Glutathione reductase activity recovered normally when cell growth and DNA synthesis were inhibited in the cells, but it failed to recover when protein synthesis was inhibited. Therefore, the inactivation of glutathione reductase appears irreversible, and the recovery of enzymatic activity is dependent on the synthesis of new protein. Continuous incubation with 19.8 +/- 0.4 microM BCNU resulted in a 50% inhibition of cell growth. A 1-hr incubation with 7.3 +/- 0.8 microM BCNU resulted in a 50% loss of viability as measured by a soft agar clonogenic assay. These experiments quantify the inhibition of glutathione reductase by BCNU and the recovery of enzyme activity in the context of the toxic effects of the compound. A clinically useful inhibitor of glutathione reductase will require a wider difference between the concentrations required for enzyme inhibition and cytotoxicity than BCNU provides.
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PMID:Characterization of the inhibition of glutathione reductase and the recovery of enzyme activity in exponentially growing murine leukemia (L1210) cells treated with 1,3-bis(2-chloroethyl)-1-nitrosourea. 340 Dec 59

Delivery of the bifunctional alkylating agent, PTT.119 [p-F-L-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy-HCl], into tumor cells is significantly greater compared to L-phenylalanine mustard (L-PAM) as demonstrated by the 2-fold reduction in PTT.119 dosage required to reduce the viable L1210 cell fraction by 50% (TCD50). This increased uptake and consequent cytolytic efficacy observed in Dulbecco's phosphate buffer was more apparent in culture medium; under this physiologic condition the TCD50 concentration of PTT.119 was 5 times lower than L-PAM. PTT.119 entry into leukemia cells was examined using competition transport assays assessing the ability of the tripeptide to compete with various amino acids and nonmetabolizable substrates for carrier receptors of the L, A and ASC transport systems. A 1-min exposure to a 1- to 50-fold excess of PTT.119 prior to addition of radiolabeled substrates significantly reduced within 60 s both sodium-dependent and sodium-independent uptake of leucine, methionine, threonine and alpha-[1-14C]-aminoisobutyric acid (AIB), but not MeAIB. In complimentary studies, L1210 cells were protected from PTT.119 cytolysis by an 8,000-fold excess of AIB, whereas beta-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH) only abrogated tripeptide cytotoxicity by 95-97% even at BCH:PTT.119 ratios of 200,000. Leucine and methionine protection were significantly less effective; the TCD50 of leucine and methionine were 3.23 and 2.4 microM, respectively, compared to 11.41 microM for AIB and 7.96 microM for BCH. In addition, MeAIB and phenylalanine were totally unable to protect L1210 cells from PTT.119-induced cytolysis. The data indicate that L121 cells actively transport PTT.119 primarily by the BCH-sensitive, AIB-sensitive, MeAIB-insensitive L carrier system. A second, BCH-insensitive, AIB-sensitive and MeAIB-insensitive carrier which is also involved in tripeptide uptake is probably the ASC system.
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PMID:Multiple transport pathways for L1210 cells: uptake of PTT.119, a bifunctional alkylator with carrier amino acids. 341 61

A series of 2-alpha-L-rhamnopyranosylnitro[1,2,4]triazolo[1,5-a] pyridine C-nucleosides was synthesized from the condensation oa thioiminoether with nitro-2-pyridylhydrazines. Catalytic reduction afforded the corresponding amino derivative. A 1',2' unsaturated C-nucleoside was also obtained by two different routes. Selective oxidation gave the 3'- and 4'-ketonucleosides. The cytotoxic properties of the nucleosides, as well as their effect on viral transformation and replication, were described. The nitro derivatives inhibit viral replication, but at toxic doses; the introduction of a keto function leads to a product which inhibits the replication of murine leukemia virus (MuLV) at noncytotoxic concentrations. The amino derivatives have no significant antiviral effect.
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PMID:2-l-Rhamnopyranosyl[1,2,4]triazolo[1,5-a]pyridine. 4' and 3' Oxidation products. Synthesis and structure-activity relationships. 627 59


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