Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of non-Hodgkin's lymphoma showed a phenotypic and genotypic cell lineage switch twice during nine years of his clinical history; first, T-cell type, pleomorphic small cell lymphoma developed, followed by B-cell type, diffuse centroblastic/centrocytic lymphoma, and finally T-zone lymphoma without follicles again developed, from which AST-1 cultured cell line was established. Karyotype analysis demonstrated a shared abnormal chromosome, der(1)t(1;?)(p36;?), among the first relapsed B-cell tumor, the second relapsed T-cell tumor and AST-1 cell line. Furthermore, T-cell receptor (TCR) gamma gene rearrangement bands of the same size were observed in the first relapsed B-cell tumor and the second relapsed T-cell tumor as well as AST-1 cell line. These results suggested that both relapsed tumors of different cell lineages are derived from a common malignant clone, presumably a committed lymphoid stem cell. A unique translocation, t(2;14)(q37;q11.2), which may involve TCR delta/alpha gene complex, was observed in the second relapsed tumor and AST-1 cells. To attempt to isolate the breakpoint of this translocation, the configuration of TCR delta/alpha gene complex was studied. The result showed that two rearrangements of TCR alpha gene detected with J alpha probes were the products of the normal TCR rearrangement process, and were not involved in the translocation at this region. This patient, together with the AST-1 cell line, provided us a unique opportunity to study the development and clonal evolution of malignant lymphoma.
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PMID:Phenotypic and genotypic lineage switch of a lymphoma with shared chromosome translocation and T-cell receptor gamma gene rearrangement. 131 86

Medical records of 11 cats with lymphoma involving large granular lymphocytes were reviewed. All 9 cats tested were FeLV-negative. Ten cats had a history of anorexia, lethargy, vomiting, or diarrhea, and had lymphoma involving abdominal viscera. The most common site of tumor in these cats was the jejunum. One cat had cutaneous masses caused by dermal and epidermal infiltration with neoplastic large granular lymphocytes. The most common hematologic abnormality was leukocytosis, characterized by neutrophilia with a left shift (7 cats); 2 cats had a left shift without neutrophilia. None of the cats had lymphocytosis, but immature large granular lymphocytes were found in the blood of 4 cats. The most common serum biochemical abnormalities were hypoalbuminemia (10 cats), hypocalcemia (10 cats), hypoproteinemia (9 cats), high aspartate transaminase activity (9 cats), and hyperbilirubinemia (8 cats). Large granular lymphocytes were characterized by abundant cytoplasm containing distinct azurophilic granules that varied in size and number. The most common cytochemical staining pattern included detection of alpha-naphthyl butyrate esterase, acid phosphatase, and beta-glucuronidase activities. On examination of histologic sections, granules stained weakly eosinophilic with Giemsa and moderately with periodic acid-Schiff reaction. Ultrastructurally, the granules appeared membrane bound and contained an electron-dense matrix in 4 cats.
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PMID:Lymphoma involving large granular lymphocytes in cats: 11 cases (1982-1991). 142 72

The effect of a muramyl dipeptide derivative (B30-MDP) on the augmentation of antitumour immunity against highly metastatic L5178Y-ML25 mouse lymphoma cells was examined in CDF1 (Balb/c x DBA/2) mice. Mice immunized with a mixture of X-irradiated tumour cells (10(3)) and B30-MDP (100 micrograms) on 7 days prior to challenge by viable tumour cells displayed a significant decrease in metastasis towards the target organs, liver and spleen, compared with that of untreated mice. Immunization of mice with the mixture on day 5 or 7 after tumour challenge, when the level of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in sera of mice inoculated with viable tumour cells was observed to be normal, caused less metastasis than immunization with X-irradiated tumour cells alone. Sensitization with X-irradiated tumour cells admixed with B30-MDP induced almost two times higher cytotoxicity of spleen cells against L5178Y-ML25 lymphoma cells than sensitization with X-irradiated tumour cells without B30-MDP. In contrast, cytotoxic activity of spleen cells against another target, L1210 lymphoma cells derived from BDF1 mice, was not observed by immunization with X-irradiated L5178Y-ML25 cells with or without B30-MDP. Specific lysis by splenic cells of the immunized mice against L5178Y-ML25 cells decreased to the normal level when T cells were deleted from the immunized spleen cells by the treatment of rabbit anti-mouse Thy1.2 antibody and rabbit complement. These results indicate that B30-MDP is able to augment a specific tumour immunity due to the enhancement of cytotoxicity mediated by T lymphocytes, and is useful as an immunopotentiating agent for active immunization of inactivated tumour cells.
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PMID:B30-MDP, a synthetic muramyl dipeptide derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice. 144 33

All cases of liver tumor referred to the King Faisal Specialist Hospital and Research Centre in Saudi Arabia during 2.5 years were reviewed. Hepatocellular carcinoma, 104 cases, was considerably more common than metastatic carcinoma with unknown primary, 15 cases. Lymphoma presenting as liver tumor occurred in three cases and there were no cases of cholangiocarcinoma. There were only two cases of benign tumor, both hemangioma. Hepatocellular carcinoma was characterized by a male predominance of 6:1, positive hepatitis B surface antigen in 60%, presentation with an enlarged, hard liver in over 90%, a systolic-diastolic bruit over the mass in 45%, a single highly echogenic lesion in the right lobe on ultrasound in 80%, and rapid progression. The serum AST (aspartate aminotransferase, serumglutamic oxalacetic transaminase [SGOT]) was abnormal in 97% and was higher than the alanine aminotransferase (ALT) in 93% of cases compared with 17% in 100 consecutive cases of chronic active hepatitis. Sixty-six percent of patients with hepatocellular carcinoma had serum AFP greater than 200 ng/ml. Excluding five cases of germ cell tumor (none involving the liver), and pregnant patients, serum AFP was less than 200 ng/ml in all other patients in whom it was measured between 1979 and 1981. A practical approach to the diagnosis of hepatocellular carcinoma is outlined. Biopsy does not appear to be indicated in many cases of advanced hepatocellular carcinoma.
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PMID:Hepatic tumors in Saudi Arabia. A practical approach to diagnosis. 257 17

Lymphoplasmacytoid (lpc) and small cell centrocytic (scc) lymphoma are the two major sub-types of diffuse low grade non-Hodgkin's Lymphoma (NHL) within the Kiel classification. The presentation features and outcome for all 112 patients with these diagnoses (60 lpc, 52 scc) managed at St Bartholomew's Hospital between 1972 and 1986 are presented. The outcome for these patients is compared with that for patients with follicular and high grade lymphomas managed at this hospital during the same period. Nineteen of the 112 patients had localized (stages I-IIE) disease. In 18 of these cases the primary site of disease was extranodal, the gastrointestinal tract being involved in 12 cases. The survival for patients with localized disease was excellent. Eighteen are currently alive with median follow-up of 8 years. Ninety-three patients had advanced disease. A high incidence of splenomegaly, hepatomegaly, bone marrow and peripheral blood involvement was observed in both histological subgroups. A monoclonal paraprotein band was detected in the serum of nearly 50 per cent of patients with advanced lpc lymphoma. Patients with advanced disease were treated with either chlorambucil or cyclophosphamide, vincristine and prednisolone (CVP). The outcome was similar for both histological groups. Survival for these patients was poor (median 40 months) with less than 20 per cent surviving 5 years. Advanced age, elevated aspartate transaminase and failure to respond to treatment were identified by multivariate regression analysis as adverse prognostic factors.
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PMID:Lymphoplasmacytoid and small cell centrocytic non-Hodgkin's lymphoma--a retrospective analysis from St Bartholomew's Hospital 1972-1986. 290 57

Etoposide is a schedule-dependent cytotoxic drug with high single agent activity in small-cell lung cancer and lymphoma. Despite its clear dose-dependent myelosuppressive activity, dose-dependent evidence of its anti-tumour activity is harder to demonstrate. A number of reports have correlated haematological toxicity with pharmacokinetic and physiological parameters, which explains some of the variability in dynamic effects that exists between patients. Recent reports have also suggested that anti-tumour response may be related to plasma etoposide concentration. In our own studies we have investigated factors that influence the pharmacodynamic effects of etoposide, principally with regard to haematological toxicity, and these studies have highlighted a number of patient groups who are at risk. Impaired renal function causes a reduction in clearance of etoposide, resulting in increased systemic exposure and more profound myelotoxicity. A 30% dose reduction in this group is recommended to normalise the area under the plasma concentration-time curve (AUC). Patients with low serum albumin concentrations (< 35 g/l) also showed significantly worse haematological toxicity, but with no apparent change in total drug pharmacokinetics. There was, however, an increase in the free drug fraction in this group due to decreased protein binding, such that the free drug AUC was similar to that found in patients with renal dysfunction. This would also indicate that a dose reduction of around 30%-40% is required in this patient group. Patients with normal albumin levels but liver enzyme values (aspartate transaminase or gamma-glutamyl transpeptidase) more than 3 times the upper limit of normal also had a less marked but significant increase in neutropenia. In patients with normal organ function, age was the only significant factor in predicting the degree of leukopenia/neutropenia, and increasing age was also associated with decreasing drug clearance and an increase in drug AUC. A small dose reduction and/or careful monitoring is required in this patient group. Further studies are required to elucidate further the relationship between the pharmacokinetics of etoposide and its pharmacodynamics, particularly with regard to anti-tumor activity, and to determine the role of individualised therapy, based on a pharmacokinetic parameter, in reducing the dynamic variability and optimising the use of this drug.
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PMID:Etoposide dosage and pharmacodynamics. 807 31

beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival.
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PMID:Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas. 847 38

The anti-CD30 immunotoxin (IT) Ber-H2/saporin is effective in patients with refractory Hodgkin's disease. However, responses are short and partial, one of the main reasons being the inability to repeat IT doses because of formation of human antibodies against the murine antibody and/or the toxin. To overcome this problem, we constructed two new anti-CD30 ITs by covalently linking the mouse monoclonal antibody Ber-H2 to the type 1 ribosome-inactivating proteins (RIPs) momordin (MOM) and pokeweed antiviral protein from seeds (PAP-S), which do not cross-react with each other or with saporin. Both ITs inhibited protein synthesis by Hodgkin's disease and anaplastic large-cell lymphoma (ALCL)-derived CD30+ target cell lines with a very high efficiency (IC50 ranging from < 5 x 10(-13) M to 2.75 x 10(-11) M, as RIP). In a SCID mouse model of xenografted CD30+ human ALCL, a 3d treatment with non-toxin doses of Ber-H2/MOM (50%LD50), started 24 h after transplantation, prevented tumour development in about 40% of the animals and significantly delayed tumour growth rate in the others. Main toxicity signs in mice and rabbits were dose-related increase of serum transaminases (AST and ALT) and creatine phosphokinase (CPK). LD50 (as RIP) in Swiss mice was 7 mg/kg for Ber-H2/MOM and 0.45 mg/kg for Ber-H2/PAP-S. Sequential administration of two anti-CD30 ITs (Ber-H2/MOM and Ber-H2/saporin) was well tolerated and did not result in formation of antibodies cross-reacting and with the two plant toxins. The results presented in this paper suggest that in the future, sequential administration of anti-CD30 humanized antibodies linked to antigenically distinct type 1 RIPs (saporin, MOM, PAP-S) should be feasible.
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PMID:Anti-CD30 (BER=H2) immunotoxins containing the type-1 ribosome-inactivating proteins momordin and PAP-S (pokeweed antiviral protein from seeds) display powerful antitumour activity against CD30+ tumour cells in vitro and in SCID mice. 861 80

A temporary elevation of serum alkaline phosphatase has been described in young children who have no evidence of liver or bone disease. This phenomenon has been termed benign hyperphosphatasemia of infancy. Its occurrence is described in three children undergoing chemotherapy for acute lymphoblastic leukemia and lymphoma. All three children were in remission and in the consolidation or maintenance phase of their therapy when the hyperphosphatasemia occurred. All children were also receiving methotrexate (IM and IV), oral 6-mercaptopurine, and oral sulfamethoxazole/trimethoprim. Although these agents are associated with hepatotoxicity, other liver transaminases (ALT, AST) remained at normal concentrations, and there was an elevation only in the bone isoenzyme of alkaline phosphatase, thus making hepatic toxicity an unlikely etiology for the hyperphosphatasemia. No alteration in chemotherapy was necessary for resolution of the elevated alkaline phosphatase in these children.
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PMID:Benign transient hyperphosphatasemia in children with leukemia and lymphoma. 927 28

Malignant histiocytosis, as defined by Rappaport, is now known as a manifestation of malignant lymphoma, the majority of which is the T-cell type. However, unlike the typical presentation of most non-Hodgkin lymphomas, this condition presents with atypical features mimicking acute hepatitis or infectious mononucleosis. The latter diagnosis is often made because of the occurrence of atypical mononuclear cells on the peripheral blood films. This is clearly seen in the seven patients we report where the initial diagnoses were that of viral fever or hepatitis. Some characteristics were found in these patients to differentiate the condition from infectious mononucleosis (IMS) and acute hepatitis (AH): paucity of lymph nodes, cholestasis and prolonged prothrombin time (PT) which is atypical IMS; persistent fever, thrombocytopaenia and disproportionately high aspartate aminotransferase which is unusual in AH in the absence of any drug or alcohol history. The PT is the most important prognosis factor. Early diagnosis and treatment led to improved survival in an otherwise aggressive and rapidly fatal condition.
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PMID:Hepatic manifestation of malignant histiocytosis: a case study. 905 6


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