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)

Teorell's fixed charge theory for membrane ion permeability was utilized to calculate specific ionic permeabilities from measurements of membrane potential, conductance, and specific ionic transference numbers. The results were compared with the passive ionic conductances calculated from the branched equivalent circuit membrane model of Hodgkin Huxley. Ionic permeabilities for potassium, sodium, and chloride of crayfish (Procambarus clarkii) medial giant axons were examined over an external pH range from 3.8 to 11.4. Action potentials were obtained over this pH range. Failures occurred below pH 3.8 during protonation of membrane phospholipid phosphate and carboxyl, and above pH 11.4 from calcium precipitation. In general, chloride permeability increases with membrane protonation, while cation permeability decreases. At pH 7.0, PK = 1.33 X 10(-5), PCl = 1.49 X 10(-6), PNa = 1.92 X 10(-8) cm/s. PK: PCl: PNa = 693:78:1. PCl is zero above pH 10.6 and is opened predominately by protonation of epsilon-amino, and partially by tyrosine and sulfhydryl groups from pH 10.6 to 9. PK is activated in part by ionization of phospholipid phosphate and carboxyl around pH 4, then further by imidazole from pH 5 to 7, and then predominately from pH 7 to 9 by most probably phosphatidic acid. PNa permeability parallels that of potassium from pH 5 to 9.4. Below pH 5 and above pH 9.4, PNa increases while PK decreases. Evidence was obtained that these ions possibly share common passive permeable channels. The data best support the theory of Teorell, that membrane fixed charges regulate permiability and that essentially every membrane ionizable group appears involved in various amounts in ionic permeability control.
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PMID:Ionic permeability of K, Na, and Cl in crayfish nerve. Regulation by membrane fixed charges and pH. 1 19

The promising results obtained with Fludara I.V. (fludarabine phosphate) treatment in the common indolent B-cell neoplasms have led to their further evaluation in other unusual B-cell malignancies, in Hodgkin's disease, and in T-cell diseases. A significant response rate has been found among patients with macroglobulinemic lymphoma, those with prolymphocytic leukemia or prolymphocytoid variant of chronic lymphocytic leukemia, and those with mycosis fungoides. The limited therapeutic data in hairy-cell leukemia and in Hodgkin's disease are also interesting.
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PMID:Fludarabine phosphate therapy in other lymphoid malignancies. 169 85

Fludara I.V. (fludarabine phosphate) is a purine analogue with a high level of activity in a variety of indolent lymphoproliferative malignancies, including chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphomas (NHL), cutaneous T-cell lymphoma, macroglobulinemia, and hairy-cell leukemia. The high response rate in relapsed and refractory patients with CLL suggests that Fludara I.V. is the most active single agent for this condition. Nevertheless, a number of issues for the future development of Fludara I.V. must be considered: the optimal dose, schedule, and route of administration (intravenous v oral) remain to be determined. To improve on single-agent results, combinations of Fludara I.V. with other agents are under development for patients with CLL and NHL. Phase III clinical trials will be performed to compare Fludara I.V. with standard therapy versus the combination regimen in previously untreated patients with CLL. A similar study is under consideration for low-grade NHL. Companion immunologic and biologic studies will be an integral component of these trials to provide a more rational approach to staging and treatment, and to increase our knowledge of the biology of these disorders.
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PMID:Issues for the future development of fludarabine phosphate. 169 86

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
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PMID:Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. 170 43

The bispecific monoclonal antibody (Bi-MAb) HRS-3/AP-1 was developed by somatic hybridization of the 2 mouse hybridoma cell lines HRS-3 and AP-1, which produce monoclonal antibodies with reactivity against the Hodgkin's- and Reed-Sternberg cell-associated CD30 antigen and alkaline phosphatase, respectively. After an active incubation with alkaline phosphatase, respectively. After an active incubation with alkaline phosphatase, purified whole immunoglobulin molecules and F(ab')2 fragments of the Bi-MAb were equally effective in converting a relatively noncytotoxic prodrug, mitomycin phosphate (MOP), into mitomycin alcohol, which was 100 times more toxic to the Hodgkin's- and Reed-Sternberg cell line L540 (CD30+) than MOP. The cytotoxic activity of MOP was unaffected when the cells were pretreated with either the Bi-MAb or the enzyme alone. The Bi-MAb HRS-3/AP-1 did not bind to HPB-ALL cells (CD30-) and was not able to activate MOP on these cells. In cocultivation experiments with HPB-ALL and L540 cells, the activation of MOP by the Bi-MAb HRS-3/AP-1 and alkaline phosphatase led to considerable cytotoxicity against the antigen-negative bystander cells. Thus, this immunotherapeutic approach might be effective in tumors in which not all the tumor cells express the respective tumor antigen.
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PMID:Specific activation of the prodrug mitomycin phosphate by a bispecific anti-CD30/anti-alkaline phosphatase monoclonal antibody. 217 12

The author has performed in vivo investigations of the methotrexate (MTX) accumulation, kinetics and polyglutamate metabolism in erythrocytes, neutrophils and myeloid bone marrow cells during clinical MTX therapy of patients with acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma and psoriasis. On the basis of these studies the clinical applicability of monitoring erythrocyte MTX concentrations in children with ALL and adult psoriasis patients have been evaluated. To accomplish this task a set of methods has been developed: 1) An automated enzymatic assay adapted for a centrifugal analyzer was used to measure MTX concentrations between 10 and 60 nmol/l in erythrocytes and serum. 2) For the study of MTX kinetics in myeloid cells, age fractionated erythrocytes and HPLC fractionated methotrexate polyglutamates a sequential radioligand binding assay with a range of 1-8 (and 1-16) nmol/l was employed. 3) Discontinuous Percoll gradients of increasing densities were used to separate myeloid cells and erythrocytes of increasing mean cell age. Declining reticulocyte counts and erythrocyte-aspartate aminotransferase activity were taken as parameters of increasing mean erythrocyte age. 4) In order to study MTX polyglutamate metabolism a high performance liquid chromatography (HPLC) procedure was set up using tetrabutylammonium phosphate in acetonitrile in an automatically generated gradient buffer system. The MTX polyglutamates were separated, and the concentrations determined by the radioligand binding assay. The individual polyglutamates were identified by comparisons with the retention times of MTX polyglutamate standards (MTX-glu1+2+3+4+6+7) which were detected spectrophotometrically at 304 nm. During 24 hour infusions MTX was incorporated predominantly in the proliferating myeloid bone marrow cells before appearing in circulating neutrophils about seven days later. Evidence for MTX incorporation in the erythroid precursors of the bone marrow was provided by demonstrating high MTX content in density fractionated reticulocyte enriched erythrocyte populations. During weekly low dose MTX treatment the erythrocyte MTX concentration reached a constant level (steady state ery-MTX) after 4-6 weeks. MTX concentrations in age fractionated red blood cells and the terminal decline of the ery-MTX and its polyglutamate forms after cessation of MTX administration revealed that maintenance of the steady state ery-MTX depended on three conditions: 1) The amount of MTX added to the circulation via MTX containing reticulocytes. 2) The in vivo efflux of MTX from circulating erythrocytes, and 3) The loss of MTX with age dependent destruction of red blood cells. The in vivo efflux of MTX accounted for a loss of MTX which was 3-4 times greater than the amount that was lost with age dependent erythrocyte destruction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo methotrexate kinetics and metabolism in human hematopoietic cells. Clinical significance of methotrexate concentrations in erythrocytes. 217 86

Fourteen patients with malignant tumors of bone (ten osteogenic sarcomas, one Ewing's tumor, one giant-cell tumor, two non-Hodgkin's lymphomas), plus one patient with a synovial cell sarcoma, who had been treated by standard extremity-conserving chemotherapy regimens, were examined before treatment by means of localized phosphorus 31 magnetic resonance spectroscopy. Thirteen (86%) of 15 examinations were successful, and 100% of successful examinations showed metabolic abnormality in the tumor. Tumors contained excess adenosine triphosphate and inorganic phosphate, an unusual peak of phosphomonoester, consistent with excessive glycolysis in tumors. The intratumor pH was normal in the 12 bone tumors, but acidic in the single soft-tissue sarcoma (pH 6.8). Metabolic response was observed in all seven patients monitored during chemotherapy, with the earliest examinations being performed two days after first treatment. An increase in the inorganic phosphate level, loss of adenosine triphosphate, and loss of phosphomonoester indicated tumor response; loss of all abnormal metabolites (two of seven patients) indicated regression of the tumor. Tumor relapse was accompanied by reappearance of abnormalities in the magnetic resonance spectrum. Phosphorus 31 magnetic resonance spectroscopy offers a unique means of determining the early response of these malignant tumors to therapy as well as predicting their relapse.
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PMID:Osteosarcoma and other neoplasms of bone. Magnetic resonance spectroscopy to monitor therapy. 347 51

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) was purified from 3 liters of serum-free conditioned medium of the Hodgkin's tumor cell line L428 KSA. The conditioned medium contained a high specific activity of 2.5 X 10(5) units of total colony-stimulating factor per mg protein. Colony-stimulating factor activity was determined by colony formation by human fetal liver cells or mouse bone marrow cells. The latter bioassay discriminated colony-stimulating factor 1, a subclass specific for monocyte/macrophage production, and G-CSF, specific for granulopoiesis, from GM-CSF. The starting material contained predominantly GM-CSF with CSF-1 and G-CSF constituting 10% and 12%, respectively, of the total activity. A seven-stage purification scheme was employed. The first stage involved concentration by batch chromatography on calcium phosphate gel. Subsequent stages involved gel filtration on Ultrogel AcA44, affinity chromatography on concanavalin A-Sepharose, batch chromatography on calcium phosphate gel and high-performance liquid chromatography on C1 reversed-phase (TSK TMS-250), gel permeation and C8 reversed-phase columns. The purified material showed a single disperse band, having an Mr of 30,000, by silver staining on sodium dodecyl sulfate polyacrylamide gel electrophoresis. An amino-terminal sequence of 20 amino acids was determined in a gas-phase sequencer with 500 ng of purified material. The sequence was identical to that predicted from the cDNA sequence. It was active on human fetal liver cells with half-maximum colony formation at 1 X 10(-12) M, but was not active on mouse bone narrow cells.
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PMID:Human granulocyte-macrophage colony-stimulating factor purified from a Hodgkin's tumor cell line. 353 1

A retrospective analysis of staging results from 308 patients with Hodgkin's disease (HD) was performed in order to relate clinico-pathological findings with respect to the liver to other staging results and to prognosis. Thirty-four patients had clinically enlarged liver, 80 had increased serum-enzyme levels indicating possible liver damage, but only 10 patients had biopsy-proven histologic evidence of HD in the liver (7 primary biopsies, 3 re-biopsies). Among the prognostic correlations not only advanced stage and liver infiltrates were connected to poor prognosis, but also--even in early stages--elevated serum enzyme values (S-GOT and alkaline phosphate).
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PMID:The liver in Hodgkin's disease--I. Clinico-pathological relations. 688 20

Reports of acute nonlymphoblastic leukemia occurring after successful treatment of Hodgkin and non-Hodgkin lymphoma (NHL) are appearing with increasing frequency. Two years after completion of LSA2-L2 therapy for stage III, poorly differentiated lymphocytic lymphoma, a 16-year-old boy developed a preleukemic state characterized by a refractory macrocytic anemia with excess blasts, dyshematopoiesis, abnormal cluster:colony ratio on in vitro bone marrow culture, and acquired deficiencies of erythrocyte pyruvate kinase, triose phosphate isomerase, and adenylate kinase. Four months later acute myeloblastic leukemia was evident. The RNA index determined by flow cytofluorometry was increased. Four marker chromosomes were found and involved complex translocation of chromosomes 11 and 17 (t11;l17) in 100% of the cells, and chromosomes 4 (t4q;4) in 10% of the cells. A thorough literature search uncovered four other reports of acute nonlymphoblastic leukemia occurring in children treated for NHL and a total of 58 cases in the adult and pediatric age groups. Over 50% of the patients had AML, were mean over 50 years of age, and were treated with radiotherapy and chemotherapy. It is anticipated that additional cases of second malignancies will be reported in this population of patients whose outlook for the curability of the primary malignancy is 75%.
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PMID:Acute myeloblastic leukemia following non-Hodgkin lymphoma in an adolescent. A report of a case with preleukemic syndrome, and review of the literature. 700 54


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