Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies with interference contrast microscopy reveal that platelets undergo a typical shape change within 30--60' after venepuncture, i.e. swelling, formation of large tentacles, tiny protrusions and vesicles at the platelet surface. This "shape change" can be observed in citrated blood and PRP, heparinized blood and EDTA-blood as well. It is enhanced by low incubation temperatures (4 degrees C, 10 degrees C) and delayed at 37 degrees C as compared with room temperature. An increased number of primarily shape changed platelets is found if platelets are strongly mechanically irritated at blood sampling. The shape change is partly reversible in vitro, it is completely or almost completely reversible in vivo. Some antiaggregating agents inhibit the in vitro shape change at varying degrees (Bencyclan, SH 869 greater than ASA greater than D-Propranolol). The shape change is partly inhibited after oral or i.v. administration of ASA. A typical transformation of platelets into "spheric" forms can be observed following the addition of Bencyclan, SH 869 and D-Propranolol to PRP in vitro. The spontaneous "primary shape change" which occurs in PRP or blood after blood sampling is probably different from the secondary ADP-induced shape change. The primary shape change may influence the results of different platelet function and aggregating tests. The shape change kinetics of "healthy" subjects and patients with Hodgkin's disease differ significantly. The described method may gain more clinical interest in the future.
 ...
PMID:[Primary shape change of platelets in vitro (author's transl)]. 72 25

1. The contribution of ATP-sensitive K+ (K+ATP) channels to the rapid increase in cellular K+ efflux and shortening of action potential duration (APD) during early myocardial ischaemia and hypoxia remains controversial, because for the first 10 min of ischaemia or hypoxia in intact hearts cytosolic [ATP] remains about two orders of magnitude greater than the [ATP] causing half-maximal blockade of K+ATP channels in excised membrane patches. The purpose of this study was to investigate this apparent discrepancy. 2. During substrate-free hypoxia, total, diastolic and systolic unidirectional K+ efflux rates increased by 43, 26 and 103% respectively after 8.3 min in isolated arterially perfused rabbit interventricular septa loaded with 42K+. APD shortened by 39%. From the Goldman-Hodgkin-Katz equation, the relative increases in systolic and diastolic K+ efflux rates were consistent with activation of a voltage-independent K+ conductance. 3. During total global ischaemia, [K+]o measured with intramyocardial valinomycin K(+)-sensitive electrodes increased at a maximal rate of 0.68 mM min-1, which could be explained by a less than 26% increase in unidirectional K+ efflux rate (assuming no change in K+ influx), less than the increase during hypoxia. APD shortened by 23% over 10 min. 4. During hypoxia and ischaemia, cytosolic [ATP] decreased by about one-third from 6.8 +/- 0.5 to 4.3 +/- 0.3 and 4.6 +/- 0.4 mM respectively, and free cytosolic [ADP] increased from 15 to 95 and approximately 63 microM respectively. 5. To estimate the percentage of activation of current through K+ATP channels (IK,ATP) necessary to double the systolic K+ efflux rate (comparable to the increase during hypoxia), K+ efflux during a single simulated action potential was measured by blocking non-K+ currents under control conditions and after IK,ATP was fully activated by metabolic inhibitors. Activation of 0.41 +/- 0.07% of maximal IK,ATP was sufficient to double the systolic K+ efflux rate. The equivalent amount of constant hyperpolarizing current also shortened the APD in the isolated myocytes by 41 +/- 5%, compared to the 39% APD shortening observed during hypoxia in the intact heart. 6. The degree of activation of IK,ATP expected to occur during hypoxia and ischaemia was estimated by characterizing the ATP sensitivity of K+ATP channels in the presence of 2 mM-free Mgi2+ and 0, 10, 100 and 300 microM-ADPi in inside-out membrane patches excised from guinea-pig ventricular myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:ATP-sensitive K+ channels and cellular K+ loss in hypoxic and ischaemic mammalian ventricle. 159 62

A chemical plant, where an increased number of non-Hodgkin's lymphomas and myelomas had been observed, was monitored for genotoxic effects occurring in peripheral mononuclear leukocyte samples from 76 exposed workers. Biochemical markers sensitive to DNA repair and drug metabolism were used as the indicators of genotoxic risk. Unscheduled DNA synthesis (UDS) and covalent binding induced by N-acetoxy-N-acetyl-2-aminofluorene (NA-AAF) and constitutive and gamma ray induced adenosine diphosphate ribosyl transferase (ADPRT) activities were highly and significantly elevated over the corresponding values for a control group of 48 postal workers. Microsomal and soluble epoxide hydrolases and glutathione transferase activities directed towards trans-stilbene oxide and 1-chloro-2,4-dinitrobenzene were not significantly altered in the exposed group. The exposure in this factory was complex, involving over 100 chemicals including several well known carcinogens. However, no apparent significant associations to exposure could be established.
 ...
PMID:Biological effects in a chemical factory with mutagenic exposure. II. Analysis of unscheduled DNA synthesis and adenosine diphosphate ribosyl transferase, epoxide hydrolase, and glutathione transferase in resting mononuclear leukocytes. 313 75

A young women affected by Hodgkin's disease developed chronic autoimmune thrombocytopenic purpura. Splenectomy induced normalization of her platelet count, but hemorrhagic symptoms did not disappear. The patient's platelets did not aggregate in response to collagen and ADP and the IgG fraction of the patient's plasma induced the same defect in normal platelets. The women's IgG recognized glycoproteins IIb and IIIa of normal platelet membranes. Prednisone therapy induced the disappearance of bleeding symptoms and the normalization of platelet aggregation.
 ...
PMID:Severe platelet dysfunction in a patient with autoantibodies against membrane glycoproteins IIb-IIIa. 359 62

Activity of adenosine deaminase (EC 3.5.4.4) was studied in thrombocytes of donors and patients with various hematological diseases. The enzymatic activity was decreased in acute leukemia, chronic myeloleukemia, chronic leukemia and blast transformation myeloma, microspherocytic and hypoplastic anemias. Variable level of the activity was observed in chronic lympholeukemia and non-Hodgkin disease. In all the diseases studied functions of thrombocytes were altered after treatment with various aggregating agents (ADP, thrombin, collagen, adrenaline, ristomycin).
 ...
PMID:[Platelet adenosine desaminase in various hematological diseases]. 406 12

The effects of adenosine 5'-triphosphate (ATP) on voltage-clamped and dissociated rat hippocampal neurons was investigated. Over 30% of neurons possessed ATP-activated inward currents at a holding potential of -70 mV. The ED50 for these currents was 150 mu M. At this concentration they were blocked by suramin (1 mM), indicating the involvement of P2-purinoceptors. The P2 purinoceptor agonist potency was 2-methylthio ATP > ATP > ADP > alpha,beta-methylene ATP, thus identifying these purinoceptors as belonging to the P2x subclass. The reversal potential for the ATP-activated currents was -45 +/- 8 mV. Ion substitution experiments showed that the permeability ratio for K+/Na+/Cs+/Cl-, was 18:3:2:1, according to the Goldman-Hodgkin-Katz equation, so that ATP activates cationic and anionic conductances in hippocampal neurons.
 ...
PMID:ATP-activated cationic and anionic conductances in cultured rat hippocampal neurons. 892 81

A high risk of venous thromboembolism or an increased bleeding tendency has been reported in patients with clinically diagnosed or occult cancer. That is why, in this study, the presence of platelet dysfunction in patients with newly diagnosed Hodgkin's disease was investigated. Platelet aggregation studies were performed in 31 patients with a mean age of 27.53+/-2.75 years and in 31 healthy volunteers with a mean age of 24.37+/-3.21 years. None of the patients had a history or a finding of bleeding diathesis or thromboembolism. A Lumi-Dual platelet aggregometer (Chrono-Log Corporation, Model 450) was used for platelet aggregation in platelet-rich plasma. Platelet aggregation responses were evaluated with ADP, collagen, epinephrine, and ristocetin. No significant difference could be found when compared with the results of healthy volunteers. In five of the patients, a primary, but not a secondary, response to ADP (2 microg/ml) was obtained (p < 0.02). Platelet dysfunction was not found in patients with newly diagnosed Hodgkin's disease in this study. One of the various pathogenic mechanisms of tumour-related thrombosis or haemorrhagic diathesis may play a role in oncological patients; for this reason, each patient should be investigated individually.
 ...
PMID:Lack of platelet aggregation abnormality in Hodgkin's disease. 1203 20

Denileukin diftitox (Ontak) is a novel recombinant fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domain of diphtheria toxin linked to human IL-2. Denileukin diftitox specifically binds to IL-2 receptors on the cell membrane, is internalized via receptor-mediated endocytosis and inhibits protein synthesis by ADP ribosylation of elongation factor 2, resulting in cell death. This article focuses on the clinical trial that led to the US FDA approval of the drug for cutaneous T-cell lymphoma in 1999, and other investigational studies for hematologic malignancies, recurrent and refractory chronic lymphocytic leukemia, non-Hodgkin B-cell lymphoma, graft-versus-host disease and autoimmune disease, demonstrating the activity and adverse effects of the drug.
 ...
PMID:Optimizing denileukin diftitox (Ontak) therapy. 1868 57

Despite relative success of therapy for Hodgkin's lymphoma (HL), novel therapeutic agents are needed for patients with refractory or relapsed disease. Recently, anti-PD1 immunotherapy or treatment with the anti-CD30 toxin conjugate brentuximab vedotin (BV) have been associated with remissions; however, the median responses of complete responses (CRs) with the latter were only 6.7 mo. To obtain curative therapy, other effective agents, based on HL biology, would have to be given in combination with BV. Hodgkin's Reed-Sternberg (HRS) cells secrete cytokines including IL-6 and -13, leading to constitutive activation of JAK/STAT signaling. In the present study the JAK1/2 inhibitor ruxolitinib reduced phosphorylation of STAT3 and STAT6 and expression of c-Myc in the HL cell line HDLM-2. These changes were enhanced when, on the basis of a matrix screen of drug combinations, ruxolitinib was combined with the Bcl-2/Bcl-xL inhibitor Navitoclax. The combination augmented expression of Bik, Puma, and Bax, and attenuated Bcl-xL expression and the phosphorylation of Bad. The use of the two-agent combination of either ruxolitinib or Navitoclax with BV or the three-agent combination strongly activated Bax and increased activities of cytochrome c and caspase-9 and -3 that, in turn, led to cleavage of poly(ADP ribose) polymerase and Mcl-1. Either ruxolitinib combined with Navitoclax or BV alone prolonged survival but did not cure HDLM-2 tumor-bearing mice, whereas BV combined with ruxolitinib and/or with Navitoclax resulted in a sustained, complete elimination of the HDLM-2 HL. These studies provide scientific support for a clinical trial to evaluate BV combined with ruxolitinib in select patients with HL.
...
PMID:Augmented efficacy of brentuximab vedotin combined with ruxolitinib and/or Navitoclax in a murine model of human Hodgkin's lymphoma. 2681 57