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

In a clinical phase II study nine patients (five men and four women; mean age 48 [42-58] years) in an early stage of chronic lymphatic leukaemia (CLL) of the B-cell type were treated with recombinant alpha-2b interferon (IFN alpha-2b), initially at a dosage of 5 mega units subcutaneously three times weekly, but in some cases reduced to 2.5 or raised to 10 mega units. Duration of treatment has been 15-36 months. Through-flow cytometry in seven patients demonstrated a definite fall in circulating B1-positive lymphocytes. Lasting partial remission (duration of 106-134 weeks) was achieved in four patients, in a further four the condition remained stable. A recurrence was noted in the patient with the initially highest lymphocyte count (52,000/microliters) after 28 weeks, control being achieved only after 64 weeks of chemotherapy. Side effects were flu'-like symptoms and (in two instances) depression. In three patients there was a clear rise in serum immunoglobulin concentrations as sign of IFN alpha-2b-induced increased immune response, while in four HLA-DR expression on monocytes was doubled. It is concluded that early treatment of CLL with IFN alpha-2b may delay the onset of necessary chemotherapy, any antibody-deficiency may be improved and survival time may ultimately be lengthened.
 ...
PMID:[Interferon alfa-2B in chronic lymphatic leukemia of the B-cell type]. 237 39

The human Mx, an interferon (IFN)-alpha- and IFN-beta-induced 76-kd protein, is a homolog (Mx-homolog) to the murine Mx protein, which is necessary and sufficient to provide adequate resistance against influenza virus in murine cells and in mice. Leukocytes from 36 patients with tumors (chronic myelogenic leukemia, hairy cell leukemia, and malignant melanoma) were monitored for their Mx-homolog content before, during, and after rIFN-alpha-2b therapy. Before therapy, only one patient was slightly positive for Mx-homolog. All 36 patients showed a significant increase of Mx-homolog in their mononuclear cells within the first day of IFN therapy. During therapy, the Mx-homolog levels remained elevated. After cessation of treatment, the Mx-homolog content in the mononuclear cells decreased slowly; within 2 weeks, it was about 20-30% of its value during therapy. However, even after 3 weeks, the Mx-homolog was still detectable. The maximally induced Mx-homolog concentration showed a significant correlation to the IFN dose given in vivo. These data indicate that the Mx-homolog is an excellent marker for monitoring the activity of IFN during IFN therapy. In addition, the in vivo endogenous activation of the IFN system might be detectable by the determination of the Mx-homolog despite the lack of circulating IFN.
 ...
PMID:Emergence and decay of the human Mx homolog in cancer patients during and after interferon-alpha therapy. 238 Jul 45

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.
 ...
PMID:A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. 240 92

The effect on retroviruses of two transition metal complexes of known antiviral activity, 4-methyl-2-amino-pyridine-palladium-chloride (MAP) and cis-dichloro-diammine-platinum(II) (cis-DDP) has been investigated. The experiments included the evaluation of the action of compounds on virus particle-associated reverse transcriptase in exogenous assays, on virus propagation in persistently infected cell cultures and on virus infectivity in mice. In disrupted viruses and in the absence of excess protein, the reverse transcriptase was inhibited by MAP but not by cis-DDP. The same results were obtained when examining the activity of the virus-associated RNA polymerase of influenza virus A/WSN. Both compounds did not inhibit the replication of retroviruses in cell cultures, except at high dose levels which exerted toxic action on both cells and virus formation. The leukemogenicity of Rauscher murine leukemia virus was strongly inhibited when the virus had been incubated with MAP before inoculation. A similar treatment with cis-DDP did not influence viral leukemogenicity. Despite somewhat different results with both compounds tested, we conclude from the present results that the above mentioned compounds cannot be considered as antiretroviral drugs.
 ...
PMID:[The biological effects of coordination compounds of transitional metals. 6. Effect of 4-methyl-2-aminopyridine-palladium chloride and cis-dichlorodiammine-platinum(II) on retroviruses and the virus-associated RNA polymerase of the influenza virus]. 243 60

Interferons are new and effective agents in the treatment of various haematological neoplasias. Alpha-interferon (natural or recombinant) has a high efficacy (90% response rate) in hairy cell leukaemia. Complete remissions are, however, rare and definite cure of the disease is unlikely. Alpha-interferon induces haematological remissions in about two thirds of patients with chronic myeloid leukaemia and leads to a reduction in Philadelphia chromosome in about 40% of patients. It is uncertain, however, whether this treatment will actually prolong the life of these patients as compared with conventional treatment. Alpha-interferon has a beneficial effect in some patients with low malignant non-Hodgkin lymphomas (in particular follicular lymphomas). The response rate in myeloma is rather small (20%). Gamma-interferon is not effective in hairy cell leukaemia, non-Hodgkin lymphoma and myeloma. It is, however, of some efficacy in chronic myeloid leukaemia (the response rate in lower than with alpha-interferon) and possibly has some effect in patients with acute myeloid leukaemia and myelodysplastic syndromes. The toxicity of interferons (alpha and gamma) consists of an influenza-like syndrome during the first days of treatment. Low doses of alpha-interferon show virtually no long-term toxicity. However, bone and muscular pain is sometimes dose-limiting with intermediate doses (5 to 15 million units) of alpha-interferon.
 ...
PMID:[Interferon therapy in hematologic neoplasms]. 245 54

Some 3'-blocked pyrimidine analogs were synthesized and tested as inhibitors of replication of human immunodeficiency virus (HIV) and Moloney-murine leukemia virus (MuLV). The analogs were of 3 kinds: (1) analogs of 3'-azido-3'-deoxythymidine (AZT) in which the C-5 CH3 of the base was exchanged for H (AZU) or C2H5 (AZEU); (2) 3'-fluoro-3'-deoxythymidine (FLT) and analogs thereof, in which the C-5 CH3 of the base was exchanged for H (FLU), C2H5 (FLEU) or nC3H7 (FLPU); (3) the threo analogs of AZT (AZT increases) and AZU (AZU increases). All analogs were less active inhibitors of HIV replication than AZT, except FLT, which was as active as AZT. The 3'-fluoro analogs and AZEU did not inhibit MuLV replication at non-cytotoxic concentrations. Oral administration of FLT to MuLV-infected mice result in antiviral effects only at toxic drug levels. AZU and FLU were less potent inhibitors of HIV replication than AZT or FLT, but the 2'-deoxy uridine analogs were less cytotoxic to human embryonic fibroblasts than the thymidine analogs. The 5'-triphosphates of AZU, AZT, AZEU, FLT and FLEU were tested as inhibitors of the HIV- and MuLV-reverse transcriptases. Ranking of the Ki/Km values for HIV-RT resulted in the following order of potency of the 5'-triphosphates AZT = FLT greater than AZU greater than AZEU greater than FLEU. The 5'-triphosphates of AZEU, FLT and FLEU did not inhibit the MuLV-RT, which explains, in part, the lack of effect of these analogs against MuLV replication. The threo forms (azido "up") of AZU and AZT were less active inhibitors of HIV replication than the erythro forms (azido "down"). A 15N-NMR and 1H-NMR study showed that the furanose moieties of analogs with the azido function "up" assume a conformation distinct from that of the analogs with azido "down". This is due to intramolecular stabilisation of the "N" conformer in the threo ("up") diastereomer, due to interaction of the azido functions with the nucleobase and possibly the OH group of C-5' of the furanose. As discussed, this conformation might explain the decreased biological activity of threo forms compared with the erythro forms.
 ...
PMID:An analysis of the inhibition of replication of HIV and MuLV by some 3'-blocked pyrimidine analogs. 246 76

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biologic response modifiers: the interferon alfa experience. 248 96

The gp52 envelope glycoprotein of Friend spleen focus-forming virus (SFFV) is a recombinant molecule derived from Friend murine leukemia virus (MuLV) by various deletions, insertions, and substitutions. The SFFV gp52 glycoprotein, unlike MuLV envelope glycoproteins, is defective in transport to the cell surface. Only 3-5% of gp52 eventually reaches the cell surface as a processed form (gp65). Although gp52 lacks cytoplasmic tail residues found in MuLV glycoproteins, we have previously shown that this deletion is not responsible for its defective transport. In order to investigate the basis for the defective transport of gp52, we have examined the folding and assembly of gp52 molecules into oligomeric molecules. CV-1 cells infected with vaccinia virus recombinants expressing SFFV gp52 were pulse labeled and the cell extracts were fractionated by velocity centrifugation through sucrose gradients. Immediately after a 10-min pulse, gp52 was detected as a monomer in the upper part of the sucrose gradient (fractions 12 and 14) and it remained as such after a 2-h chase period. However, the processed form, gp65, was found in a lower part of the gradient (fraction 8) after a 2-h chase. The position of gp65 was found to correspond to the position of trimeric influenza hemagglutinin which was analyzed on a parallel sucrose gradient, suggesting that gp65 also exists as a trimer in this fraction. These results indicate that changes in the external domain of gp52 result in improper folding of the glycoprotein molecule, and suggest that this lack of oligomerization is responsible for the defective transport of the molecules. Only those molecules that do form oligomeric structures are transported to the Golgi complex and undergo further oligosaccharide processing, and transport to the cell surface.
 ...
PMID:The spleen focus-forming virus envelope glycoprotein is defective in oligomerization. 254 80

Tubuloreticular inclusions (TRI) have been observed in the rough endoplasmic reticulum of blood lymphocytes and monocytes in two cases of Reye's syndrome initiated by influenza infections. Tubuloreticular inclusions are seen in these mononuclear leukocytes during the acute phase of illness, but not during convalescence. Since TRI have been demonstrated in peripheral mononuclear leukocytes in patients with acquired immunodeficiency syndrome, systemic lupus erythematosus, and certain viral infections including T-cell leukemia, it may be that the finding of TRI in Reye's syndrome reflects a viral infection and/or immune dysfunction, if such association is not proved to be fortuitous.
 ...
PMID:Leukocyte tubuloreticular inclusions in Reye's syndrome. 258 24

The toxicity, pharmacokinetics, and hematologic effects of granulocyte-macrophage colony-stimulating (GM-CSF) were studied in a phase I/II trial of 16 patients with myelodysplastic syndrome (MDS). The GM-CSF was administered subcutaneously (SC) daily so as to achieve prolonged blood levels and to establish an outpatient treatment regimen. Four dose levels were administered for ten days: 0.3 microgram/kg/d (three patients), 1.0 microgram/kg/d (three), 3.0 micrograms/kg/d (four), and 10.0 micrograms/kg/d (six). The most common toxicities were fever and a flu-like syndrome, which were dose-dependent. The maximum-tolerated dose was 10.0 micrograms/kg/d, which induced severe rigors (two patients), fever greater than 40 degrees C (one), severe bronchospasm (one), and WBC 60,000 (one). In one patient, refractory anemia with excess blasts in transformation (RAEB-T) progressed to acute nonlymphocytic leukemia after two doses of GM-CSF, and the patient died of leukemia that did not respond to chemotherapy. After doses of 3.0 and 10.0 micrograms/kg, serum GM-CSF levels peaked at 3.8 to 6.3 hours, and persisted for 14 and 24 hours, respectively. Circulating granulocytes (neutrophils and bands) increased in a dose-dependent manner, as 11 of 13 patients who received greater than or equal to 1.0 microgram/kg/d responded with a two- to 194-fold increase. Although the neutrophils usually returned to pretreatment levels shortly after stopping GM-CSF, two patients continue to exhibit an elevation of neutrophils for 6 months. Dose-related increases in circulating monocytes and eosinophils were also noted. Transient increases in platelet and reticulocyte counts were observed in two and three patients, respectively. Five of the 16 patients later received maintenance GM-CSF at 3 micrograms/kg/d for 2 to 9 weeks. All showed a dramatic increase in neutrophils after 2 weeks. Thereafter, despite continued therapy, the neutrophil count in four patients declined markedly. In conclusion, GM-CSF is well tolerated by the SC route and induces striking, but usually temporary, improvement in the neutropenia of MDS. Larger prospective phase III trials will determine the duration of hematologic responses and the impact on infection, morbidity, and mortality.
 ...
PMID:Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects. 265 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>