Remission of methotrexate-resistant rheumatoid arthritis after receiving 5-fluorouracil for colon cancer.
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Biomedical subjects
Publications and source records attributed to J Mejer.
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Deoxycytidine kinase (dCK) is important in the 5'-phosphorylation of deoxynucleoside analogs. Like dCK, thymidine kinase 2 (TK2) catalyzes the initial step of the phosphorylation of dcyd to dCTP. Thymidine is a strong inhibitor of the dCK activity of TK2. We examined the ratio of the dcyd phosphorylation carried out by dCK and by TK2 (dCK/TK2-dcyd) in lymphocytes from CLL patients and from donors. In the CLL lymphocytes we found a 3.5-fold average increase. Therefore, we conclude that addition of thymidine in the treatment of CLL with deoxynucleoside analogs will not be of any advantage. Furthermore, our results can explain earlier findings in CML and AML lymphocytes where the ara-C phosphorylation was twice the dcyd phosphorylation.
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A case of visceral leishmaniasis in a 39-year-old woman is presented. It is the first case in Denmark, in an otherwise healthy person. The patient was infected on a short holiday in Malta.
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The activities of the enzymes cytidine deaminase (CDD), deoxycytidine kinase (dCK), adenosine deaminase (ADA), and purine nucleoside phosphorylase (PNP), have been investigated in the promyelocytic leukemia cell line HL60. The activities of the enzymes corresponded well with that seen in acute myeloid leukemia cells except, that the CDD activity was very low in the HL60 cells. Induction of differentiation in HL60 cells by 1,25 dihydroxy D3 resulted in an increase in CDD from 12 to 247 nmol/h/mg and a decrease in ADA from 1326 to 896 nmol/h/mg, while the activities of dCK, and PNP were unchanged. Retinoic acid, another used inducer of differentiation, gave no changes of the enzyme activities. The increase in CDD activity induced by 1,25 dihydroxy D3 was prevented by inhibition of protein synthesis, whereas inhibition of proliferation of the cells did not abolish the increase of CDD. The changes correspond well with the differences seen between immature and mature myeloid cells. The results may have consequences for the interpretation of results obtained with cytostatics, which are metabolized by the enzymes.
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The activities of five clinically important enzymes of purine metabolism have been determined in lymphocytes from 62 patients with various types of solid tumors. The activity of purine nucleoside phosphorylase was increased in all patient groups studied, i.e. small cell bronchogenic carcinoma (n = 30), carcinoma of the breast (n = 17) and other tumors (n = 15), compared to cells form normal donors. Activities of adenosine deaminase, adenine phosphoribosyltransferase (APRT), hypoxanthine (guanine) phosphoribosyltransferase (HGPRT), and 5'-nucleotidase (5'-NUC) vary little from control values, except for lower levels of APRT in lymphocytes from patients with carcinoma of the breast. In patients with small cell bronchogenic carcinoma, enzyme levels were also determined in granulocytes, where increased APRT activity was found. Following cytostatic treatment of these patients, significant decreases were seen in lymphocytic HGPRT and 5'-NUC activities.
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Eighty-one adult outpatients with endoscopically confirmed gastric ulceration were treated with cimetidine (1 g/day). In addition, the patients were allocated at random to either intensive antacid treatment or placebo treatment. This part of the study was double-blind. It was found that additional antacid treatment had no effect on ulcer healing and symptoms in cimetidine-treated gastric ulcer patients. The results were similar in patients with corpus ulcers and patients with prepyloric ulcers.
Some purine metabolizing enzymes of lymphocytes and granulocytes were determined in 13 patients with cirrhosis of the liver and in a control group consisting of 18 healthy blood donors. Furthermore cytidine deaminase (EC 3, 5, 4, 5) (CRD) activity was determined in the granulocytes of these patients and in 16 controls. An increase of adenosine deaminase (EC 3, 5, 4, 4) (ADA) activity was found in granulocytes (P less than 0.01) as well as in lymphocytes (P less than 0.01) of the cirrhotic patients as compared to controls. Purine nucleoside phosphorylase (EC 2, 4, 2, 1) (PNP) activity in granulocytes and lymphocytes was identical in the two groups. In lymphocytes of cirrhotic patients decreased hypoxanthine guanine phosphoribosyltransferase (EC 2, 4, 2, 8) (HGPRT) (P less than 0.01), adenine phosphoribosyltransferase (EC 2, 4, 2, 7) (APRT) (P less than 0.02) and adenosine kinase activities (EC 2, 7, 1, 20) (AK) (P less than 0.05) were demonstrated. 5'-nucleotidase (5'-N (EC 3, 1, 3, 5) activity in lymphocytes of cirrhotic patients was slightly increased, the increase being correlated to the level of serum gamma globulin. Granulocytes from cirrhotic patients showed a decrease of CRD (P less than 0.05). The finding that ADA activity is increased in mature lymphocytes and granulocytes from cirrhotic patients argues against the possibility that increase of lymphocytes ADA activity is a consequence of malignant transformation or immaturity.
Four previously healthy Danish homosexual men developed Kaposi's sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi's sarcoma.
Initial phosphorylation and deamination of cytosine arabinoside (Ara-C) and the natural metabolite deoxycytidine (CdR) were estimated in cell free extracts of leucocytes from patients with CML and controls. Phosphorylation of CdR had been increased while deamination of CdR in extracts of CML cells from peripheral blood had been decreased compared with normal leucocytes. Comparing the ratios between Ara-C and CdR phosphorylation it was revealed that these were twice as high in CML cells as in normal leucocytes, whereas no difference was found when comparing ratios between Ara-C and CdR deamination. From these discoveries it is proposed that Ara-C can be combined with CdR with advantage, because apparently CdR protects the normal cells more than the malignant ones.