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)

Our objective has been to prepare a biotinylated affinity probe for the active centre of a protease associated with the surface of tumour cells. We employed three model systems in which easily recognisable tumour cells containing the active protease were used as targets for the biotinylated affinity probe. These were: squamous cell carcinoma, leukaemia cells in muscle and outgrowths of prostate carcinoma cells grown in three dimensional collagen gels. The presence of the bound biotinylated affinity probe was demonstrated by its ability to bind Texas-red labelled streptavidin with the results that the tumour cells exhibited red fluorescence. This binding was shown to be competitive with 9-amino acridine, a compound known to bind to the active centre of the target protease. This technique depends upon the affinity of the active centre of an enzyme for a competitive inhibitor and therefore should be applicable to other enzyme systems employing suitable ligands for their active centres.
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PMID:Labelling of tumour cells with a biotinylated inhibitor of a cell surface protease. 166 33

The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1-10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury.
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PMID:Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog. 169 38

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.
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PMID:Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells. 172 26

Analyses of the aminoterminal propeptide of type III procollagen (PIIINP) in the cerebrospinal fluid (CSF) of 55 children and five young adults without any structural central nervous system (CNS) lesion are reported. The concentration was age-dependent, in that infants and small children had quite high values, whereas the concentration remained relatively constant after the age of 1.5 years. The concentrations of PIIINP in the CSF of 44 children with acute lymphoblastic leukemia (ALL) were prospectively determined at the time of diagnosis and during treatment, since deposition of type III collagen is known to occur during fibroproliferative responses triggered by inflammation. Chemical arachnoiditis is known to be associated with intrathecal methotrexate therapy in children with leukemia. The mean concentration in these children at diagnosis (5.8 micrograms/l +/- SD 2.8 micrograms/l) did not differ from that in age-matched controls (6.7 micrograms/l +/- SD 3.2 micrograms/l). Depending on type of the disease, the children were treated according to two different protocols. PIIINP concentrations were significantly higher during the therapy phases which included intrathecally administered methotrexate (P less than 0.001) than at diagnosis of the disease. Corticosteroid treatments were always associated with a significant decrease in PIIINP concentrations (P less than 0.01 and P less than 0.001 in the two groups, respectively), irrespective of the therapy phase. The results suggest that an increase in PIIINP concentration in the CSF of children with ALL is an indicator of a fibroproliferative response in the arachnoid. Corticosteroids may repress this response and possibly also prevent the development of adhesions in the arachnoid.
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PMID:Aminoterminal propeptide of type III procollagen in cerebrospinal fluid. Variation with age and in childhood leukemia. 176 20

We determined the reference interval for the carboxyterminal propeptide of type I procollagen (PICP), an indicator of the synthesis of type I collagen, in cerebrospinal fluid (CSF) by studying 32 infants and children, ages less than or equal to 15 years. The concentration of PICP is age dependent, with particularly high concentrations occurring in children younger than 1.5 years. In older children the concentration is stable (reference interval 20-92 micrograms/L). We also investigated the possibility that PICP in CSF could reflect local fibroproliferative changes in the arachnoid in a cohort of 42 children with acute lymphoblastic leukemia who were monitored by repeated sampling in connection with intrathecal therapy. Initially, there was no difference in PICP between the children with newly diagnosed leukemia and the controls. PICP concentrations were significantly higher (P less than 0.01) during intrathecal methotrexate therapy, with median values above the reference interval. Continuous corticosteroid treatment was associated with a significant decrease in PICP (P less than 0.02 and P less than 0.01, respectively, in two groups treated according to different protocols), close to the lower limit of the reference interval. Intrathecally administered methotrexate and systemic corticosteroid treatment are known to be associated with the development of arachnoiditis and with general repression of collagen synthesis, respectively. We conclude that PICP in CSF is a sensitive indicator of local fibroproliferation and ongoing collagen synthesis.
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PMID:Carboxyterminal propeptide of type I procollagen in cerebrospinal fluid in childhood and in children with leukemia undergoing intrathecal treatment. 186 95

The Mov13 mouse strain carries a mutation in the alpha 1(I) procollagen gene which is due to the insertion of a Moloney murine leukemia provirus into the first intron. This insertion results in the de novo methylation of the provirus and flanking DNA, the alteration of chromatin structure, and the transcriptional inactivity of the collagen promoter. To address the mechanism of mutagenesis, we reintroduced a cloned and therefore demethylated version of the Mov13 mutant allele into mouse fibroblasts. The transfected gene was not transcribed, indicating that the transcriptional defect was not due to the hypermethylation. Rather, this result strongly suggests that the mutation is due to the displacement or disruption of cis-acting regulatory DNA sequences within the first intron. We also constructed a Mov13 variant allele containing a single long terminal repeat instead of the whole provirus. This construct also failed to express mRNA, indicating that the Mov13 mutation does not revert by provirus excision as has been observed for other retrovirus-induced mutations.
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PMID:Retrovirus-induced insertional mutagenesis: mechanism of collagen mutation in Mov13 mice. 192 37

Fourteen constituents were isolated from the roots of Salvia miltiorrhiza f. alba. Two of them were new compounds and were named 1,2,15,16-tetrahydrotanshiquinone (I) and tanshinaldehyde (II). The others were identified as Ro-090680 (III), dihydroisotanshone I (IV), danshexinkun B (V), miltirone (VI), nortanshinone (VII), hydroxytanshinone II-A (VIII), tanshinone I (IX), dihydrotanshinone I (X), tanshinone II-A (XI), cryptotanshinone (XII), methylenetanshiquinone (XIII), methyltanshinonate (XIV), I and III showed inhibitory activity against P388 Leukemia cell in vitro. III was reported to be a potent inhibitor of rabbit platelet aggregation induced by collagen.
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PMID:[Chemical studies of Salvia miltiorrhiza f. alba]. 195 62

Photodynamic therapy is a new concept for in vitro evaluation of bone marrow clearance in leukemia. This treatment eliminates 99.9999% of leukemic cells, but under the same conditions over 50% of normal bone marrow cells are damaged. WR-2721, a thiol compound, is reported to except a protective effect for bone marrow against radiation therapy. This study analyzed the protective effect of WR-2721 during photodynamic therapy with hematoporphyrin derivative. Mice hemopoietic cells were exposed to laser light after sensitization by hematoporphyrin, with or without WR-2721 at 3 dose levels (250, 500, 750 mg/kg). The efficacy of protection was evaluated by GM-CFU assay in collagen gel medium. Results showed significant protection at 25 and 50 j/cm2 (p less than 0.05), but at 75 j/cm2 irradiation only the 750 mg/kg dosage remained protective. The protective factor of WR-2721 is 1.65 (95% confidence interval: 1.38-1.99) WR-2721 is protective against photodynamic lesions but this protection is diminished by increased irradiation energy. The best results are obtained with a dose of 750 mg/kg though this appears to be toxic. Further studies are needed to evaluate the action of WR-2721 on leukemic cells before the use of WR-2721 in bone marrow clearance.
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PMID:The protection of hemopoietic mice progenitors by WR-2721 during photodynamic therapy. 196 91

Mast cells are resident in tissues, particularly in association with endothelial and epithelial cell basement membranes, and increase at sites of inflammation, injury, and fibrosis. Although mast cells are known to both release and generate proinflammatory molecules in response to inflammatory stimuli, little is known about their normal biologic function. Here we demonstrate that IL-3-dependent mouse PT18 mast cells, mouse bone marrow-derived mast cells, and rat basophilic leukemia cells express large amounts of mRNA for collagen IV, laminin, and heparan sulfate proteoglycan. Western blot analysis confirmed that mast cells synthesize and secrete significant amounts collagen IV and laminin B1 and B2 chains. These data suggest that mast cells may contribute to normal tissue repair and/or the early overproduction of basement membrane components seen in a variety of fibrotic conditions.
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PMID:Murine mast cells synthesize basement membrane components. A potential role in early fibrosis. 199 45

Clinical and pathological analysis were performed on 127 cases of deep mycoses diagnosed by autopsy during the 24 years between 1964 and 1987 in Juntendo University Hospital. The following findings were obtained. 1) There has been a tendency for the number of mycoses to increase each year, especially notable for candidiasis and aspergillosis. 2) Underlying diseases were, in order of incidence, various hematologic diseases, solid tumors, inflammatory diseases and collagen diseases; the most common were various types of leukemia. 3) Candidiasis was often observed in patients with gastrointestinal tract cancers. Aspergillosis was often observed in patients with collagen diseases. 4) Regarding the visceral distribution of mycoses, aspergillosis was observed in the lung, candidiasis was observed in the lung, kidney and intestinal tract in decreasing order, and cryptococcosis was also observed in the lung and central nervous system. 5) There was a probability of fungal infections occurring in cases of lymphopenia. 6) A fever was present at the time of hospitalization in many cases of aspergillosis, and the presence of an indwelling catheter was a common feature in cases of candidiasis. 7) Fungemia was frequently observed in candidiasis, but very rarely in cases of aspergillosis. 8) The large amounts of corticosteroid hormones and blood transfusions were suspected as causative factors of fungal infections.
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PMID:[Clinical and pathological analysis of deep mycoses]. 206 3


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