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)

Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 50 patients with plasma cell dyscrasias using a commercially available immunoenzymatic assay kit. There were 40 patients with multiple myeloma (MM), 5 patients with monoclonal gammopathy of undetermined significance (MGUS), 3 patients with solitary plasmacytoma (SPC), 1 patient with chronic myelogenous leukaemia and multiple myeloma (CML/MM), and 1 patient with plasma cell leukaemia (PCL). We found that serum sIL-6R concentrations were higher in MM patients (62.53 +/- 38.85 ng/ml) than in 20 normal volunteers studied (36.75 +/- 13.79 ng/ml) (p < 0.01). The cut-off value of 65 ng/ml seen in 2 of our controls was arbitrarily taken as the upper limit of the control range for serum sIL-6R; according to this criterion, 14 patients with MM (35%), 1 patient with SPC, the unique patient with CML + MM, and the unique patient with PCL had elevated concentrations of the receptor. Patients with MGUS had normal sIL-6R values. In MM patients, serum sIL-6R levels correlated with the clinical phase of the disease: they were elevated in patients with early or late active disease and ranged within normal limits in patients with plateau-phase disease (p < 0.001). Thirteen of 27 patients with active MM had elevated serum sIL-6R values, i.e. 48.1%, but only 1 out of 13 patients with disease in the plateau phase, i.e. 7.7% (p < 0.05). Furthermore, in the entire group of MM patients, serum sIL-6R levels correlated with the concentrations of serum beta 2-microglobulin, (p < 0.02), CRP (p < 0.01), ferritin (p < 0.01) and LDH (p < 0.01), while they did not correlate with disease stage, haemoglobin levels, proportion of marrow myeloma cells, the values of serum IL-6, the levels of serum albumin, or the grade of bone lesions. We conclude that elevated serum sIL-6R levels should be related to the growth of myeloma cells and suggest that serum sIL-6R concentrations may be used as an indicator of disease activity.
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PMID:Serum levels of soluble IL-6 receptor in multiple myeloma as indicator of disease activity. 915 60

We studied the functional characteristics of subpopulations of cord blood-derived CD34+ cells expressing different levels of CD38 and c-kit antigens, using clonal cell culture and long-term culture with allogeneic bone marrow stromal cells or the MS-5 murine stromal cell line to assay long-term culture-initiating cells (LTC-IC) in each subpopulation. To investigate the capacity for replication, proliferation, and differentiation of each subpopulation of CD34+ cells, we also studied the correlation between LTC-IC and telomerase activity. After 5 weeks of coculture, LTC-IC accounted for one out of 32 CD34+CD38- cells and one out of 33 CD34+c-kit- cells. In contrast, the frequency of LTC-IC was low in their antigen-positive counterparts (one per 84 CD34+CD38+ cells, one per 90 CD34+c-kit(low) cells, and very low among CD34+c-kit(high) cells). It was noteworthy that some LTC-IC derived from CD34+CD38- as well as CD34+c-kit- cells generated colony-forming cells (CFCs) after up to 9 weeks of coculture. Telomerase activity was consistently low in CD34+CD38- and CD34+c-kit- cells compared to CD38+ or c-kit(high or low) cells, suggesting that CD34+CD38- or c-kit- cells are likely to be more quiescent. These results suggest that the CD34+CD38- and CD34+c-kit- cell populations are primitive stem/progenitor cells, and that the telomerase activity of these cells correlates with their proliferative capacity as well as their stage of differentiation.
Leukemia 1998 May
PMID:Human cord blood-derived primitive progenitors are enriched in CD34+c-kit- cells: correlation between long-term culture-initiating cells and telomerase expression. 959 71

The effect of leukaemia inhibitory factor (LIF) on the proliferation of prospermatogonial stem cells was tested in vitro. Pieces of 3-day-old rat testis were cultured in the presence of a range of doses of LIF alone or in combination with 1 ng mL(-1) seminiferous growth factor (SGF). Stimulation of the proliferative activity of quiescent prospermatogonia was detected immunocytochemically with a cell proliferation kit. After 24 h culture, LIF significantly increased the percentage of labelled prospermatogonia, with the peak of activity at 20 pg mL(-1). The combination of LIF and SGF resulted in a decrease in DNA synthetic activity of the germ cells. Hence, LIF and SGF play a role in local regulation at the onset of spermatogenesis in the rat testis.
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PMID:Leukaemia inhibitory factor stimulates proliferation of prospermatogonial stem cells. 962 92

We hypothesized that human hematopoietic cells displaying a CD34+, kit-, rhodamine123(low) phenotype would be highly enriched for cells with stem-like properties. To test this hypothesis, we employed fluorescence activated cell sorting (FACS) to isolate cells with this phenotype from normal light density marrow mononuclear cells (MNC). CD34+, kit+, rhodamine123(low) cells comprised from 0.05-0.01% of the total MNC population. They were small, had scant cytoplasm, and contained nuclei with dense, hyperchromatic chromatin and inconspicuous nucleoli. Additional immunophenotyping revealed that these cells were CD33-, CD38-, CD20-, and glycophorin A-. When plated in semisolid cultures containing optimal concentrations of IL-3, GM-CSF, KL, EPO, IL-6, and IL-1 these cells did not form colonies. However, when cultured over irradiated stromal cells, cobblestone areas were observed to form after 3 weeks, and harvested cells were able to initiate long-term cultures. To further demonstrate that these cells were indeed stem like, we also tested their ability to engraft and mature in immunocompromised (SCID) mice. Irradiated (400 cGy) SCID mice were transplanted with 2 x 10(3) candidate stem cells which were then injected with recombinant human growth factors every other day. Two months post-transplant the animals were sacrificed. PCR and FACS analysis of marrow and spleen cell samples revealed the presence of cells expressing human CD45 consistent with engraftment of human stem cells and the establishment of murine-human chimerism. Moreover, MNC isolated from transplanted mice formed unambiguously human BFU-E, CFU-GM and B cell colonies when stimulated with the appropriate growth factors. Accordingly, we have identified a relatively rapid and simple mechanism for isolating primitive human hematopoietic cells with stem cell-like properties. We anticipate that this strategy will be useful for experimental and therapeutic applications that require human stem cells in quantity.
Leukemia 1998 Jun
PMID:CD34+, kit+, rhodamine123(low) phenotype identifies a marrow cell population highly enriched for human hematopoietic stem cells. 963 24

We report on a case of adenovirus hemorrhagi cystitis that developed in a 49-year-old woman during intensive chemotherapy for adult T-cell leukemia. Although rapid etiologic diagnosis is essential for the effective management of viral hemorrhagic cystitis, the isolation of adenovirus from urine is often too time-cousuming. We detected the adenovirus antigen in the patient's urine using an Adenoclone direct sandwich ELISA kit (Cambridge Bio Science), which is commonly employed for the diagnosis of adenovirus conjunctivitis. Treatment consisted of intravenous vidarabine and bladder irrigation, which resulted in prompt clinical improvement. The Adenoclone kit was useful for the rapid etiologic diagnosis of adenovirus hemmorrhagic cystitis.
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PMID:[Utilization of a direct sandwich ELISA kit for rapid diagnosis of adenovirus hemorrhagic cystitis in a patient with adult T-cell leukemia]. 969 76

The cytokine stem cell factor (SCF) synergizes with IL-7 to enhance the proliferation of thymocytes. We therefore investigated the role of the SCF receptor, the protooncogene c-kit, in the pathogenesis of pediatric T-lineage malignancies. Expression and regulation of c-kit in cells from children with non-Hodgkin's lymphoma (T-NHL) or acute lymphoblastic leukemia (T-ALL) and the proliferative effect of SCF on these cells were examined in seven cell lines and 21 biopsy tumor cell preparations. Inducibility of c-kit receptors by SCF, IL-1beta, IL-2, IL-7, TGF-beta, TNF-alpha, PMA or calcium ionophore A23187 was studied by flow cytometry (FCM). C-kit receptors were detected in three out of seven T-lymphoblastic cell lines and in nine out of 21 biopsy tumor cell preparations. Upregulation of c-kit could be induced by cultivation, and to a higher extent by cultivation and addition of IL-1beta, TNF-alpha, TGF-beta or A23187. Downregulation of c-kit occurred in the presence of SCF or PMA. SCF caused a downregulation of c-kit receptors in eight of nine, and a proliferative response in three of 11 c-kit-positive T-lymphoblastic cell preparations. We conclude that c-kit is able to transduce a growth stimulatory signal in some T-lymphoblastic cells and that its expression may not be detectable in a resting metabolic or proliferative state.
Leukemia 1998 Aug
PMID:Expression and regulation of c-kit receptor and response to stem cell factor in childhood malignant T-lymphoblastic cells. 969 76

The value of flow cytometric detection of myeloperoxidase (MPO) in the differential diagnosis of acute leukemia was evaluated in 57 cases of acute leukemia and in 9 leukemia cell lines. Cells were fixed and permeabilized with Fix & Perm cell permeabilization kit at room temperature for 15 min each, and stained with anti-MPO monoclonal antibody (MPO-7) by direct immunofluorescence. One myeloid cell line, HL-60, was MPO-positive, while the other myeloid cell lines (KG-1, K-562, and MEG-01) as well as lymphoid cell lines (KM-3, NALM-6, Raji, REH, and T-ALL-1) were MPO-negative as previously described. Among acute leukemias, MPO was detected in 23 of 26 cases of acute myeloid leukemia (AML), 7 of 23 cases of B-lineage acute lymphoblastic leukemia (ALL), 1 of 6 cases of T-lineage ALL (T-ALL), and 1 of 2 cases of acute unclassified leukemia (AUL). The intensity of MPO expression in 6 of 7 B-lineage ALL cases was weak compared with AML labeling. There was no detectable cytochemical MPO in the cells of ALL, AUL, or AML that stained negative for anti-MPO. No relationship between the expression of MPO and myeloid lineage surface antigens was observed in ALL. Three cases of MPO-positive ALL and AUL could be reclassified as biphenotypic leukemia according to the revised Catovsky scoring system. These results indicate that anti-MPO is an excellent marker for the diagnosis and classification of acute leukemia and can be reliably detected by flow cytometry. This rapid technique should be a valuable addition to routine immunophenotyping of acute leukemia.
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PMID:Detection of myeloperoxidase by flow cytometry in acute leukemia. 972 60

The effect of antisense hTERT mRNA oligodeoxynucleotide on telomerase activity of leukemia cells was explored and investigated in the present study. Telomerase activity was measured by the telomerase PCR ELISA assay kit (TRAP); hTERT mRNA expression by reverse transcription polymerase chain reaction (RT-PCR) assay and gel-image system, hTERT protein by immunochemistry and flowcytometry. Results showed Incubation of leukemic cells (HL-60 and K562 cell lines) with 10 micromol/l AS PS-ODN would significantly reduce the their mRNA levels and in vitro expression of hTERT protein 24 h later, so that the telomerase activity would be significantly down-regulated or inhibited. In conclusion, the hTERT AS PS-ODN is an excellent inhibitor for telomerase activity.
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PMID:Effect of antisense hTERT mRNA oligodeoxynucleotide on telomerase activity of leukemic cells. 1209 28

Adis CommentsCerus Corporation is developing a variety of pathogen-inactivation systems, based on its Helinx technology. Three of the systems include amotosalen [S 59] as the inactivation compound. Amotosalen is a light-activated, DNA-, RNA-crosslinking psoralen compound, which is used to neutralise pathogens. The systems that utilise amotosalen are called the INTERCEPT Platelet System, the INTERCEPT Plasma System and the Allogeneic Cellular Immunotherapies (ACIT) system. The INTERCEPT Platelet System and INTERCEPT Plasma System are two of the systems that make up Cerus' INTERCEPT Blood Systems. The other system is the INTERCEPT Red Blood Cell System, which contains S 303 as the inactivation compound rather than amotosalen. Cerus' Helinx technology is able to prevent replication of DNA or RNA that is present in pathogens but not in the blood components being treated (e.g. platelets and plasma). When added to the blood components, the inactivation agent (in this case amotosalen) crosses the membrane or cell wall of the pathogen. When activated by light, amotosalen binds to the nucleic acid of the pathogen and prevents replication. This process prevents infection. INTERCEPT Platelet System: Cerus developed its INTERCEPT Platelet System, in collaboration with Baxter Healthcare, for use in blood centres. Platelets are an essential component of the coagulation process and may be required by patients undergoing surgery, cancer chemotherapy, transplantation or with bleeding disorders. The system is made up of an illuminator device, a compound absorption device and a processing kit containing amotosalen. In October 2002, the two companies announced that CE Mark approval had been received for the illuminator device for the INTERCEPT trade mark Blood System. Application of this technology to platelets is the first to be approved. As it is a new technology, the system is currently undergoing process validation in accordance with European Blood Bank GMP requirements. This validation process is currently being conducted in Denmark, France, Germany, Sweden and the UK. Marketing approval applications for the INTERCEPT Platelet System have also been submitted in Australia and Canada. In addition, the regulatory submission process has begun in the US. A phase III trial (EuroSPRITE) has been conducted in 103 patients in Europe with pooled random donor platelets. The platelets were collected using the buffy coat process. Another two 20-patient clinical trials have also been conducted in Europe, as well as a 40-patient trial using platelets collected by an apheresis collection system. Cerus has also conducted a phase III trial (SPRINT) in the US. The trial was conducted in 671 patients and used platelets collected by Baxter's apheresis collection system. INTERCEPT Plasma System: Cerus is also developing the INTERCEPT Plasma System in collaboration with Baxter Healthcare. The system also combines amotosalen, an illumination device and a compound absorption device. The two companies are currently preparing regulatory applications for the INTERCEPT Plasma System for the US. This application will be followed by a submission for CE Mark designation in Europe. Patients undergoing surgery, or transplantation, or with bleeding disorders, may require transfusions of plasma, often to control bleeding. The type of plasma is stored in frozen form and is called fresh frozen plasma (FFP). The INTERCEPT Plasma System is currently in phase IIIc development in the US. Patient enrolment in the trial is still ongoing. The trial is comparing INTERCEPT trade mark Plasma System treated versus untreated FFP in 30 patients with thrombotic thrombocytopenic purpura. Allogeneic Cellular Immunotherapies system: Cerus is also investigating the potential of its Helinx technology to improve the outcome of bone marrow transplantation procedures (used to treat leukaemia and lymphoma) through the treatmatment for many forms of leukaemia and is most effective when the donor is very closely matched to the patient for the major human leucocyte antigen (HLA) groups. As part of the transplant procedure, patients receive donor T cells to improve engraftment of the bone marrow transplant and strengthen the patient's immune system. However, donor T cells expose the patient to a high risk of contracting graft-versus-host disease (GVHD) caused by the proliferation of donor T cells, which attack the patient's healthy tissue. GVHD has a high mortality rate. Cerus' ACIT system has been developed to decrease the stringency of matching donors to patients and to inhibit the ability of donor T cells to cause GVHD. Light-activated amotosalen binds and permanently crosslinks DNA, preventing replication and thus stopping proliferation of donor T cells. Phase I development is currently being conducted in this area in the US using amotosalen as the neutralising agent. Cerus completed a phase I study investigating the safety and tolerability of its ACIT system in 2001. The study was conducted in patients receiving closely matched allogeneic bone marrow transplants for leukaemia. The company is currently collaborating with the National Marrow Donor Program in order to conduct further clinical studies in patients receiving bone marrow transplants from unmatched donors. Cerus has development, manufacturing and marketing agreements with Baxter covering the INTERCEPT Blood Systems, which includes the INTERCEPT Platelet system, the INTERCEPT Plasma System, and the INTERCEPT Red Blood Cell System. Under the terms of the agreements the two companies usually share the very early development activities. Cerus then conducts preclinical and clinical trials, while Baxter is responsible for the development of the systems disposables and devices. Following commercialisation Cerus will supply amotosalen and Baxter will supply the other components of the system and market, sell and distribute the system In January 2001, Cereus announced that it has entered into a collaborative agreement with the Pharmaceutical Division of Kirin Brewery in Japan to develop and market products for stem cell transplantation based on Cerus' proprietary Helinx technology. Under terms of the agreement, Cerus and Kirin will jointly develop the products. Cerus has received an initial license fee of US dollar 1 million. In addition it may receive up to US dollar 11 million in future payments upon achievement of development milestones. Kirin will also fund all development expenses for the Asia-Pacific region and a portion of Cerus' development activities aimed at obtaining product approval in the US. Kirin will market the products in the Asia-Pacific region, including Japan, China, Korea and Australia, and Cerus will receive a specified share of product revenues. Cerus will retain marketing rights in the rest of the world, including the US and Europe.
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PMID:Amotosalen: Allogeneic Cellular Immunotherapies system, INTERCEPT Plasma System, INTERCEPT Platelet System, S 59. 1253 21

The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System are designed to sequence the protease (PR)- and reverse transcriptase (RT)-coding regions of human immunodeficiency virus type 1 (HIV-1) pol. Studies were undertaken to determine the accuracy of this assay system in detecting resistance-associated mutations and to determine the effects of RNA extraction methods, anticoagulants, specimen handling, and potentially interfering substances. Samples were plasma obtained from HIV-infected subjects or seronegative plasma to which viruses derived from wild-type and mutant infectious molecular clones (IMC) of HIV-1 were added. Extraction methods tested included standard and UltraSensitive AMPLICOR HIV-1 MONITOR, QIAGEN viral RNA extraction mini kit, and QIAGEN Ultra HIV extraction kit, and NASBA manual HIV-1 quantitative NucliSens. Sequence data from test sites were compared to a "gold standard" reference sequence to determine the percent agreement. Comparisons between test and reference sequences at the nucleotide level showed 97.5 to 100% agreement. Similar results were obtained regardless of extraction method, regardless of use of EDTA or acid citrate dextrose as anticoagulant, and despite the presence of triglycerides, bilirubin, hemoglobin, antiretroviral drugs, HIV-2, hepatitis C virus (HCV), HBV, cytomegalovirus, human T-cell leukemia virus type 1 (HTLV-1), or HTLV-2. Samples with HIV-1 RNA titers of >or=1,000 copies/ml gave consistent results. The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System consistently generate highly accurate sequence data when tested with IMC-derived HIV and patient samples.
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PMID:Performance characteristics of the TRUGENE HIV-1 Genotyping Kit and the Opengene DNA Sequencing System. 1268 50


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