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

The responsiveness to IL-4 with and without costimulation with anti-IgM antibodies or phorbolester was studied in 35 cases of low grade non-Hodgkin lymphoma by analyzing enhancement of CD23 and HLA class II expression. The predominant phenotype responds directly to IL-4. Separate differentiation states can be distinguished according to coordinate or differential upregulation of CD23 and HLA class II molecules by IL-4 alone, and differences in responsiveness to anti-IgM antibodies. A particular subgroup of B-lymphoma cells defines a separate stage of B-cell differentiation. They fail to express high affinity binding sites for IL-4 and accordingly do not respond to IL-4-mediated signals. Cross-linking membrane IgM receptors or direct activation of protein kinase C via phorbolester induces IL-4 receptor expression and subsequent IL-4 reactivity.
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PMID:Regulation of IL-4 responsiveness in lymphoma B cells. 183 95

We studied a nine-year-old boy with severe, recurrent infections. The patient was exposed in utero to azathioprine and prednisone. He had autoimmune hemolytic anemia, bronchiectasis, and Hodgkin's disease. The patient's circulating lymphocytes were normal in number and phenotype, but stimulation of the T-cell receptor by antigens, mitogens, and monoclonal antibodies failed to induce interleukin-2-receptor expression, interleukin-2 synthesis, or lymphocyte proliferation. The early biochemical events necessary to initiate lymphocyte activation--accumulation of the second messenger diacylglycerol, activation of the enzyme protein kinase C, and elevation of the free intracellular calcium concentration--failed to occur in this patient's lymphocytes. The defect in the lymphocyte could be corrected in vitro by two agents that bypass the receptor-mediated signal mechanism (the diacylglycerol analogue phorbol and the calcium ionophore ionomycin). Further studies localized the defect in signal transduction to the interaction between cell-surface receptors and the guanine nucleotide-binding protein. We conclude that this patient's immunodeficiency was caused by a defective coupling of surface receptors to signal-transducing proteins in his T lymphocytes, resulting in failure of lymphocyte activation.
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PMID:An immunodeficiency characterized by defective signal transduction in T lymphocytes. 278 45

1. The Shaw-like voltage-activated potassium channel Kv3.1 is expressed in neurons that generate rapid trains of action potentials. By expressing this channel in a mammalian cell line and by simulating its activation, we tested the potential role of this channel in action potential repolarization. 2. NIH 3T3 fibroblasts were stably transfected with Kv3.1 DNA. Currents recorded in these cells had a threshold of activation at approximately -10 mV, showed little inactivation, and were very sensitive to blockade by 4-aminopyridine and tetraethylammonium. 3. Kv3.1 currents activated rapidly at the onset of depolarizing voltage pulses. After an initial rapid phase of activation, which could be fit by an n4 Hodgkin-Huxley model, Kv3.1 currents expressed in fibroblasts had a second, slower phase of activation, and, in some cells, a slower phase of partial inactivation, both of which could be fit with modified n4p models. 4. Cell-attached single-channel recordings indicated that the Kv3.1 channel displays two gating behaviors, a short-open-time pattern, which occurs only at the onset of depolarization, and a long-open-time pattern, which predominates during prolonged depolarizations. 5. The amplitude of Kv3.1 currents, and the probability of channel openings, was reduced by a phorbol ester activator of protein kinase C, and the action of this agent was blocked by preincubation with the protein kinase inhibitor H7 (1-[5-isoquinolinesulfonyl]-2-methyl piperazine). In contrast, the effects of dioctanoyl glycerol, which also attenuated the currents, could not be completely blocked by H7, suggesting that diacylglycerols may act on the channel by a kinase-independent pathway. 6. Incorporation of a current with the kinetics and voltage dependence of Kv3.1 currents into a model cell with a sustained inward current showed that, in contrast to other delayed-rectifier currents such as the Shaker-like Kv1.1 and Kv1.6 channels, the level of expression of Kv3.1 currents could be varied over a wide range without attenuation of action potential height. Our results suggest that the Kv3.1 channel may provide rapidly firing neurons with a high safety factor for impulse propagation.
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PMID:Electrophysiological and pharmacological characterization of a mammalian Shaw channel expressed in NIH 3T3 fibroblasts. 747 24

The activation marker CD30 is expressed on the cell surface of the malignant cells in Hodgkin's disease and a few non-Hodgkin lymphomas. We have analyzed the regulation of membrane-bound CD30 and found that the binding of a variety of anti-CD30 antibodies induced down-regulation of CD30 on cell lines. In addition, such down-modulation was also observed after treatment of the cell surface proteins with the sulfhydryl reagent iodoacetamide or after stimulation of the second messenger pathway with phorbol ester or calcium ionophore. This modulation was abolished at 4 degrees C and strongly inhibited by chelators like EDTA or 1,10-phenanthroline, whereas EGTA, a selective inhibitor of Ca(2+)-dependent proteinases and other inhibitors of serine, thiol and acid proteinases, showed no effect. The down-modulation was strengthened by Zn2+ or Cd2+, but not by other divalent cations such as Fe2+, Mn2+, Mg2+, Ca2+ or Co2+, thus indicating the involvement of a zinc metalloproteinase in CD30 modulation which can be activated by protein kinase C and by alkylation of sulfhydryl groups. Pulse-chase experiments, analysis of the CD30 glycosylation and specific measurement of the 90-kDa soluble form of CD30 (sCD30) with a sandwich radioimmunoassay revealed that CD30 down-modulation results from enhanced release of 90-kDa sCD30 by the site-specific cleavage of CD30 accomplished by a zinc metalloproteinase. This release occurs at the cell membrane without prior endocytosis.
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PMID:A zinc metalloproteinase is responsible for the release of CD30 on human tumor cell lines. 759 Dec 96

Annexin VIII is a calcium- and phospholipid-binding protein with anticoagulant activity. Annexin VIII mRNA was found to be specifically expressed in acute promyelocytic leukemia (APL) cells; it was not found in other types of acute myeloid leukemia (AML) nor in lymphoid malignancies. Using Northern blot analysis we investigated annexin VIII expression in 142 continuous human leukemia and lymphoma cell lines at the mRNA level. While the only APL cell line, NB-4, was indeed positive, other cell lines also displayed annexin VIII mRNA: 4/22 myeloid cell lines, 8/23 monocytic cell lines, 2/8 megakaryoblastic cell lines, 5/26 lymphoma-derived cell lines, 2/10 myeloma cell lines and 1/44 lymphoid leukemia cell lines. The strongest expression was seen in NB-4 and in the Hodgkin's disease derived cell line HDLM-2. Treatment of NB-4 cells with all-trans retinoic acid (ATRA) or the phorbol ester TPA induced terminal differentiation and down-regulated annexin VIII mRNA expression rapidly within a few hours; vitamin D3 was ineffective in this regard; the protein kinase C activator Bryostatin 1 up-regulated the expression. A panel of initially negative cell lines could not be induced by any of these biomodulators to transcribe annexin VIII. The half-life (T1/2) of annexin VIII mRNA was about 3-4 h using actinomycin D as transcription inhibitor. Treatment with ATRA or TPA prior to exposure to actinomycin shortened the T1/2 to 2 h while Bryostatin 1 extended it to 6h. As 21/141 non-APL cell lines were positive, annexin VIII cannot be used as a marker gene for APL cells; however, it might be associated with myelomonocytic or erythro-megakaryoblastic precursor cells. Annexin VIII gene expression might play a unique role in the proliferation and/or differentiation of leukemic cells and could be associated with the particular abnormal hemostasis of some leukemias.
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PMID:Expression and modulation of annexin VIII in human leukemia-lymphoma cell lines. 823 Dec 35

HLA-class II molecules can be induced in low-grade non-Hodgkin B lymphoma cells by either membrane IgM cross-linking or phorbolester stimulation. The ability of phorbolesters to substitute for anti-IgM antibodies in the activation of normal and malignant human B cells has been taken as evidence for the involvement of protein kinase C (PKC) in signals transduced through membrane IgM receptors (mIgR). Here we report on freshly isolated lymphoma B cells from different patients; the cells show a distinct regulation of HLA-class II expression. In certain lymphoma cases phorbol-myristate-acetate (PMA) not only fails to up-regulate HLA-class II molecules but also inhibits anti-IgM or interleukin-4 induced class II expression. This negative signal induced by PMA seems to operate specifically in HLA-class II regulation because PMA can induce other anti-IgM mediated events like blast transformation and induction of IL-4 responsiveness at the same time. Therefore these cells support the concept of functional heterogeneity in low-grade non-Hodgkin lymphoma and may represent a differentiation stage where anti-IgM antibodies and phorbolesters influence the regulation of HLA-class II expression in a contrary direction.
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PMID:Differential signal requirement for upregulation of HLA-class II molecules in human lymphoma B cells. 834 Feb 86

Bryostatin 1 (Bryo1), a macrocyclic lactone and a protein kinase C activator, is extracted and purified from the marine bryozoan Bugula neritina. In this study we describe its effect on morphology, surface immunophenotype, acid phosphatase (AcP), tartrate-resistant acid phosphatase (TRAP), proliferation and cell cycle of non-Hodgkin's B-lymphoma cell lines representing four differentiation stages. Except for the WSU-BL, a high-grade SCNCL, all other cell lines showed obvious changes in their morphology when treated with 200 nM Bryo1. Phenotypically, a dramatic decrease of CD10 and induction of CD11c and BL7 on some cell lines consistent with further B-cell differentiation was seen. The lines in control cultures showed variable expression of AcP and TRAP. Following treatment with Bryo1, there was a general increase in AcP expression except in WSU-BL line. WSU-FSCCL and WSU-DLCL were TRAP-negative but became TRAP-positive when treated with Bryo1. Cell growth and cycle analysis during treatment of different cell lines revealed evidence of strong, moderate, or no growth inhibition by Bryo1 compared with control cultures. Our results indicate that Bryo1 shows differentiation effects on low-grade FSCCL, intermediate-grade FLCL and high-grade DLCL, and stimulatory or no effect on high-grade SCNCL. Since Bryo1 does not have tumor-promoting activity, it has a potential therapeutic role as a B-cell differentiating agent.
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PMID:Differential effects of bryostatin 1 on human non-Hodgkin's B-lymphoma cell lines. 842 74

1. Voltage-gated ionic currents were recorded from cells of an immortalized neuroepithelial cell line named V1. The cell line was produced by insertion of the temperature-sensitive tsA58 allele of the SV40 large T-antigen into embryonic day 14 mouse hypothalamic cells. V1 cells display a mixed immature neural-glial phenotype and have two phenotypes, round and flat. 2. Recordings from round V1 cells demonstrate voltage-gated Na+ and K+ currents (n = 297), while no voltage-gated currents were observed in flat V1 cells (n = 45). Voltage-gated currents were recorded from cells cultured at both permissive and restrictive temperatures. 3. Internal Cs+ and external tetraethylammonium (TEA) were used to suppress outward currents. The remaining inward current has rapid activation and inactivation time constants which decreased as the test potential increased. In different cells, the amplitude of the peak inward current varied from about 50 pA to as large as 4500 pA (in 120 mM external Na+). The reversal potential for the inward current was close to the predicted Nernst equilibrium potential for Na+. Both the magnitude and reversal potential of the inward current were dependent on the external Na+ concentration. It is therefore considered to be a Na+ current, INa. 4. INa was found to be TTX resistant. About 5% of the INa was blocked by 200 nM TTX and 20 microM TTX fully suppressed the Na+ current. The apparent Kd for TTX blockade was estimated to be 1.49 microM. 5. The activation kinetics of INa could be described by a Hodgkin-Huxley model with an m3 variable. The time constants of activation and inactivation of INa are fast, similar to those of the TTX-resistant and TTX-sensitive Na+ currents in central nervous system neurons and glial cells. 6. The divalent and trivalent cations Cd2+, Co2+, Ni2+, Zn2+ and La3+ shifted the activation of INa to more positive potentials and decreased the maximal conductance in a dose-dependent manner. The apparent Kd values for blockade of the INa by Cd2+, Co2+, Ni2+, Zn2+ and La3+ were 430, 3500, 1900, 83 and 202 microM, respectively. 7. The addition of phorbol myristate acetate, an activator of protein kinase C, consistently produced a reduction in the amplitudeof INa without affecting the time course of activation or inactivation. 8. INa in V1 cells expresses a unique combination of voltage and time kinetics and sensitivity to blockade by TTX and cations. We hypothesize that this Na+ current may be expressed transiently during development of the central nervous system at the stage of development represented by the V1 cell line.
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PMID:A novel tetrodotoxin-resistant sodium current from an immortalized neuroepithelial cell line. 874 76

Conventional approaches to the treatment of malignancy are often not curative or are associated with serious complications. New approaches to treatment are needed. A variety of specific approaches to the destruction of virus-associated tumor cells are illustrated in the context of EBV-associated Hodgkin's disease and nasopharyngeal carcinoma. Viral antigens expressed by tumors may be targeted by cytotoxic T cells. Other viral antigens not naturally expressed by tumors may be induced by pharmacologic manipulations such as treatment with demethylating agents. Viral enzymes not naturally expressed by tumors such as thymidine kinase may be induced by protein kinase C activators, thus rendering tumor cells sensitive to killing by ganciclovir.
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PMID:Epstein-Barr virus as a therapeutic target in Hodgkin's disease and nasopharyngeal carcinoma. 894 6

In this paper we develop a mathematical model for the electrical activity of the afferent pathway, formed from the coupled primary and secondary sensory neurons. The primary sensory neuron possesses the electrical properties of AH neurons and morphological characteristics of Dogiel type II neurons; the secondary sensory neuron displays the tonic type of electrical behavior and has morphological features of Dogiel type III neurons. Free nerve endings of the mechanoreceptor form the receptive field of the pathway. Based on the general principles of the Hodgkin-Huxley description of excitable cells, the model simulates the following sequence of events: stretch of the receptive field initiates the dendritic potential at the mechanoreceptors; the excitation causes soma action potential development at the primary sensory neuron which is followed by soma action potential generation at the secondary sensory neuron. Numerical calculation have shown that the model is capable of reproducing different electrical patterns within the pathway under normal physiological conditions and after treatment with charybdotoxin, iberiotoxin, tetrodotoxin, omega-conotoxin GVIA, A1-A2 purinoceptor agonists, a protein kinase C activator, and a delta-opioid receptor agonist. Comparison of the computational results with the results of experiments conducted on the neurons of the submucous and myenteric plexi of the small bowel demonstrates their good qualitative and quantitative agreement.
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PMID:Electrical activity of the sensory afferent pathway in the enteric nervous system. 900 51


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