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)

Circulating immune complexes (ClC) were estimated in 78 patients of leukaemias and lymphomas by Clq deviation ELISA and PEG assay. In all leukaemias a significant elevation in ClC was seen at the time of first presentation. While in ALL a decrease occurred on therapy as partial or complete remission was achieved, no such fall was seen in AML or CML-BC when treated. ClC levels were much higher in non-Hodgkins lymphoma than in Hodgkins disease and showed a direct correlation with B symptoms and activity of the disease. The ClC levels were highest in null-ALL followed by those in common ALL and T-ALL. The mean duration of remission in patients of ALL without elevation in ClC was much longer than in those with ClC.
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PMID:Circulating immune complexes in leukaemias and lymphomas. 139 53

Circulating immune complexes (CIC) were estimated in 28 cases of Non-Hodgkin's lymphomas, Hodgkin's disease, bone and soft tissue sarcomas in the pediatric age group by polyethylene glycol (PEG) precipitation and latex agglutination inhibition (LAI) techniques. Results were compared with 25 age-matched controls. Highly significant CIC values were obtained by LAI technique (P less than 0.01) as compared to PEG pptn technique (P less than 0.05) in malignancy. However, seropositivity for CIC in lymphomas and Hodgkin's disease was 85.71 per cent by LAI test as compared to 57.14 per cent by PEG pptn test. In sarcoma group, seropositivity for CIC was 57.11 per cent by LAI test and 28.57 per cent by PEG pptn test. Combination of both these tests increases the sensitivity of immune complex detection in serum of cancer patients. CIC begin to rise in serum in early stages of neoplastic transformation, and the level of CIC is directly proportional to proliferating tumour mass in vivo.
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PMID:Role of circulating immune-complexes as prognostic indicators of lympho-reticular and mesenchymal malignancies in children. 152 15

A polyethylene glycol 6000 (PEG) mediated precipitation procedure was used to estimate the levels of CIC in sera of healthy donors and patients with Hodgkin's disease (HD). In comparison with the normal serum samples, sera from untreated HD patients showed elevated CIC levels scattered over a wider range and a mean which differed significantly. Sera from treated patients who were in clinical remission exhibited decreased CIC levels. However, the mean level in this category was still above the mean found in the normal sera. The analysis of the data showed that the sera from HD patients in Stage I and II, and with LP and MC type histology showed preferential increase in CIC levels. The analysis of these CICs in 2D-SDS-PAGE and a careful scrutiny of the polypeptide patterns obtained revealed significantly elevated amounts of a component with a Mr of 40 kD and a pI of 5.6 in CICs from the untreated HD patients. Congruent peptide maps of this component and its decreased amounts in CICs from sera of patients in remission suggests its quantitative involvement in the disease.
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PMID:Circulating immune complexes (CIC) in Hodgkin's disease. I. Levels and two-dimensional analysis. 271 24

Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 mumol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 mumol/L (9 mg/dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.
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PMID:Use of polyethylene glycol-modified uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma. 328 28

A 3.75% polyethylene glycol 6000-precipitation method was used to estimate the levels of circulating immune complexes (CIC) in pre- and postsplenectomy serum samples obtained from 34 patients suffering from Hodgkin's disease (HD). In 26 out of the 34 patients (76.47%) the postsplenectomy samples showed a considerable decrease in CIC levels compared to the levels in the presplenectomy samples. Two patients showed a marginal change while the remaining 6 patients exhibited elevated levels of CICs after splenectomy. The mean levels (in terms of OD 450 nm) in the pre- and postsplenectomy sample sets were 0.66 +/- 0.07 and 0.42 +/- 0.05, respectively (p less than 0.01). There was no apparent relationship between the interval elapsed after splenectomy (6-22 days) and the magnitude of decrease (1.7-91.8%). Patients with LP-type histology and splenic involvement formed a category that preferentially showed a substantial decrease in CIC levels after splenectomy.
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PMID:Influence of splenectomy on the levels of circulating immune complexes (CIC) in Hodgkin's disease (HD). 356 8

Sera from 28 untreated patients with Hodgkin's disease and from 120 healthy controls were investigated for the presence of circulating immune complexes using a modified 3% polyethylene glycol precipitation method with subsequent quantification of the precipitated protein. Elevated levels of precipitable protein were found in 79% (p less than 0.005) of Hodgkin's disease sera. The degree of elevation was associated with disease activity including the presence of B-symptoms. Constant and pronounced increase of precipitable protein was found in six patients with stage-III B nodular sclerosis subtype, thus exceeding the average amount of precipitable protein in healthy controls by a factor of 3-4. The erythrocyte sedimentation rate in 20 patients correlated with the amount of precipitable protein (r = 0.79). Additionally, partial component analysis of the precipitates was carried out by laser nephelometry. Immunoglobulins and complement components were identified as being major components of the precipitated material in sera both from patients and healthy controls, thus confirming the probability of the immune complex nature of the precipitates. Significant differences between patients and healthy controls concerned the amount of precipitable components. Elevation of precipitable IgM was found to be the most sensitive parameter (86% above means + 2 SD of normal controls, p less than 0.005). Increased amounts of precipitable IgG, C4, and Clq were found in 57-46% of patients' sera. Elevation of precipitable IgA and C3c were identified less often. The results suggest the quantification of precipitable immune complexes and their components to be of value as adjuncts in determining disease activity in Hodgkin's disease.
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PMID:Precipitable immune complexes in Hodgkin's disease. 661 6

Levels of circulating immune complexes (CIC) were estimated in the sera of 110 patients with Hodgkin's disease (HD) and of 103 normal subjects by polyethylene glycol precipitation method. Levels of CIC were significantly elevated in HD patients compared to normal subjects with 63% of the patients showing levels above 95th percentile of the normal. Patients with symptoms showed significantly elevated levels of CIC compared to patients without symptoms. There was a good correlation between the levels of CIC and the clinical stages, the former increasing from stage I to IV. However, no such correlation was noticed with respect to the histological type of the disease. On polyacrylamide gel electrophoresis CIC of normal subjects as well as of HD patients showed a number of protein bands. But CIC of HD patients had one additional band with approximate molecular weight of 130 000 which was absent in CIC of normal subjects.
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PMID:Circulating immune complexes in Hodgkin's disease. 683 41

Circulating immune complexes were demonstrated in about 50% sera of 70 patients with Hodgkin's disease. Circulating immune complexes were detected by using two methods. The inhibition of RF Latex agglutination detects those immune complexes which contain immunoglobulins G as antibodies. Another test applied in this work is based on the selective precipitation of soluble immune complexes by 3g% solution of polyethylene glycol (PEG). This test is suitable for further characterisation of immune complex constituents. Analyses of PEG precipitates obtained after adding PEG to sera of patients with Hodgkin's disease showed that immunoglobulin G were present in all analysed cases. In some analysed PEG precipitates beta-lipoproteins were also identified among precipitated proteins. The obtained results, therefore, suggest the possibility that detected complexes are not obviously immune complexes, but the serum protein complexes of some other type.
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PMID:[Circulating immune complexes in the serum in Hodgkin's disease]. 733 79

L-asparaginase is an enzyme which hydrolyses asparagine. Since the 1960s it has been known that some leukemic cells are deficient in asparagine synthetase and therefore cannot manufacture sufficient quantities of this essential amino acid to maintain cell viability. L-asparaginase is predominantly useful in acute lymphocytic leukemia (ALL) although responses have been noted in patients with acute myeloid leukemia, lymphoma, and rarely other tumors. L-asparaginase has been used in conjunction with methotrexate and ara-C in combination programs in leukemia. The major side-effect limiting the usefulness of L-asparaginase is allergic reactions. In addition, it is probable that neutralizing antibodies develop which shorten the half life of the drug so that the goal of depletion of plasma levels of asparagine cannot be attained or maintained. Polyethylene glycol (M.W. 5000) can be conjugated to L-asparaginase at sites not involving the active site of the enzyme. This enables free access of a small molecule, asparagine, to the active site of the enzyme but prevents uptake by the reticuloendothelial system, greatly decreasing the probability of developing antibodies against the asparaginase and prolongs the circulating half life of the drug. In a phase I/II study conducted at the M.D. Anderson Cancer Center, 37 heavily pretreated patients with refractory hematologic malignancy were treated. The age range from 15 to 73 years, median 49 years. Nineteen patients had ALL, 15 lymphoma, two myeloma, and one Hodgkin's disease. The dose levels of PEG L-asparaginase varied from 250 IU/m2 up to 8000 IU/m2. The pharmacokinetic profile demonstrated a monophasic half life consistent with a one compartment model with a single elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-asparaginase and PEG asparaginase--past, present, and future. 848 65

Owing to the high efficacy of L-asparaginase in the treatment of acute lymphatic leukaemia the enzyme was introduced into the chemotherapy schedules for remission induction of this disease shortly after results of large-scale clinical trials had become available. Since asparaginase monotherapy was associated with a high response rate but short remission duration, the enzyme is currently employed within the framework of combination chemotherapy schedules which achieve treatment response in about 90% and long-term remissions in the majority of patients. Recently initiated clinical trials have still confirmed the eminent value of asparaginase in the combination chemotherapy of acute lymphatic leukaemia and of some subtypes of non-Hodgkin lymphoma, and its important role as an essential component of multimodal treatment protocols. Despite the unique mechanism of action of this cytotoxic substance which shows relative selectivity with regard to the metabolism of malignant cells, some patients experience toxic effects during asparaginase therapy. Immunological reactions toward the foreign protein include enzyme inactivation without any clinical manifestations as well as anaphylactic shock. Severe functional disorders of organ systems result from the impaired homeostasis of the amino acids asparagine and glutamine. The changes affecting the proteins of the coagulation system have considerable clinical impact as they may induce bleeding as well as thromboembolic events and may be associated with life-threatening complications when the central nervous system is involved. Risk factors predisposing to thromboembolic complications are hereditary resistance against activated protein C and any other hereditary thrombophilia. Other organ systems potentially affected by relevant functional disorders are the central nervous system, the liver, and the pancreas, with patients who have a history of pancreatic disorders carrying an especially high risk of developing pancreatitis. Studies on the mechanisms of action and the occurrence of resistance phenomena have shown that a treatment response may only be expected if the malignant cells are unable to increase their asparagine synthetase activity to an extent providing enough asparagine to the cell; one may thus conclude that the enzyme-induced asparagine depletion of the serum constitutes the decisive cytotoxic mechanism. Independent of the asparagine depletion related cytotoxicity however, there are other mechanisms of clinical relevance like induction of apoptosis. Besides this, further influences on signal transduction cannot be excluded. Only few publications have dealt with the question of minimum trough activities to be ensured before each subsequent asparaginase dose in order to maintain uninterrupted asparagine depletion under treatment, and answers to this problem are not definitive. Clinical studies using enzymes from E. coli strains indicate that a trough activity of 100 U/l will suffice for complete asparagine depletion of the fluid body compartments with the preparations studied. These findings have been transferred to enzymes from other E. coli strains as well as those isolated from Erwinia chrysanthemi and to the PEG-conjugated E. coli asparaginases. It might be desirable to countercheck the results for confirmation or correction. The dosage and administration schedule of the various enzyme preparations required for complete asparagine depletion over a period of time have been insufficiently defined. While pharmacokinetic studies showed clinically relevant differences in biological activity and activity half-lives for enzymes from different biological sources, the findings of recently published clinical trials indicate that the therapeutic efficacy is affected when different asparaginase preparations are given by identical therapy schedules. (ABSTRACT TRUNCATED)
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PMID:Use of L-asparaginase in childhood ALL. 976 45


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