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Biomedical subjects

B Munch-Petersen

Publications and source records attributed to B Munch-Petersen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Thymidine kinase in human leukemia--expression of three isoenzyme variants in six patients with chronic myelocytic leukemia.

In six patients with untreated, chronic myelocytic leukemia (CML), the dominating thymidine kinase (TK) activity was compared with the fetal form, TK 1, from mitogen stimulated and the adult form TK 2 from unstimulated normal human lymphocytes, and with TK-1-onc, TK-3-onc and TK-4-onc. This was done in human acute, myelocytic and monocytic leukemias, using the combined thymidine/dTTP enzyme kinetics for isoenzyme characterization. TK-1-onc was found in one, TK-2-onc in two and TK-3-onc in three CML patients. The suffix -onc indicates the difference in ATP kinetics and molecular weights between the normal and the leukemic thymidine kinases. A possible relation between the isoenzyme forms and the types of leukemias is discussed.

Adenosine Triphosphate↗
PubMed1988

Azidothymidine inhibits mitogen stimulated growth and DNA-repair in human peripheral lymphocytes.

Until now, 3'-Azido-3'-deoxythymidine (AZT) is the most widely used drug in AIDS therapy, but the positive anti HIV effect of the drug is often accompanied by severe side effects such as bone-marrow suppression. In the present study, the effect of AZT on UV induced DNA strand-break rejoining and on phytohemagglutinin stimulated growth of lymphocytes from 7 healthy volunteers has been examined, and inhibitory effects of the drug was observed at therapeutic concentrations, i.e. 1-10 uM AZT.

Adolescent↗
PubMed1988

Increased number of circulating suppressor T-lymphocytes in sun-induced multiple skin cancers.

The distribution of peripheral lymphocyte subsets was studied in fifteen patients with multiple nonmelanoma skin cancers, selected according to history of ultraviolet (UV) or X-ray exposure. The skin cancer was associated with previous heavy exposure to UV light in seven patients, and past exposure to x-rays in eight patients. In the UV group, the helper T-lymphocytes/suppressor T-lymphocytes (Th/Ts) ratio was abnormally low (P less than 0.01) compared with the ratios of the x-ray and control groups. The low Th/Ts ratio was associated with an absolute increase in the number of Ts. This suggests that heavy sun exposure may cause a permanent increase in the number of Ts in certain persons. These extra T-lymphocytes may in turn prevent immune rejection of transformed keratinocytes.

Adult↗
PubMed1988

Thymidine kinase in human leukemia. Expression of the lymphoblastic isoenzyme in three patients with acute myelocytic leukemia.

The dominating thymidine kinase activity in mononuclear white blood cells from three patients with untreated acute myelocytic leukemia (AML) was compared with TK 1 from phytohemagglutinin-stimulated and TK 2 from unstimulated, normal lymphocytes. The enzyme activity in the AML cells and the stimulated lymphocytes was found to be in the same range. Regarding the combined thymidine and dTTP kinetics, the enzymes from the three AML patients resembled TK 1, but the ATP kinetics were different and the molecular weights were lower, as previously found for thymidine kinases from other leukemic cells. Therefore, the designation TK-1-onc is suggested for the thymidine kinases from the AML cells.

Adenosine Triphosphate↗
PubMed1987

Deoxycytidylate deaminase activity in non-stimulated and phytohemagglutinin-stimulated human lymphocytes, and in leukemic cells.

Deoxycytidylate deaminase isolated from normal human lymphocytes and from mononuclear leucocytes from patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia and acute monocytic leukemia has been characterized in regard to the substrate, dAMP and the allosteric regulators dCTP and dTTP. The enzymes exhibited sigmoidal initial velocity versus dCMP concentration whereas in the presence of the activator, dCTP, Michaelis-Menten kinetics were obtained. At saturating substrate concentrations dTTP acted as an allosteric inhibitor of the enzyme isolated from non-stimulated as well as from stimulated lymphocytes. However, the enzymes isolated from the leukemic cells had lost the allosteric regulation by dTTP. At low substrate concentrations the competitive inhibitor, dAMP, activated all the enzymes. This activation was abolished in the presence of dCTP which indicates that dAMP might be involved in the regulation of dCMP deaminase activity and thus influence the dCTP and dTTP pools under physiological conditions.

Aged↗
PubMed1987

Normal sister chromatid exchange in lymphocytes from patients with multiple epidermal cancer?

Exposure to toxins in the environment and due to personal habits, e.g., tobacco smoking, may increase the rate of spontaneous sister chromatid exchange (SCE). The SCE in lymphocytes from a group of 31 patients with multiple epidermal cancer, who in the past had been exposed to various skin carcinogens, as a whole exceeded that of a control group--matched by sex, age, and smoking habits--but the difference was not statistically significant (p = 0.08). The individual SCE in these patients was also statistically independent of the nature of the carcinogenic exposure. We were unable to detect correlations between the SCE and UVC-radiation induced DNA synthesis, UVC-radiation tolerance, or rate of X-ray damage repair. This suggests that the molecular mechanisms involved in SCE induction and in repair of radiation damage are basically independent.

Adult↗
PubMed1987

The nevoid basal cell carcinoma syndrome: sensitivity to ultraviolet and x-ray irradiation.

Demographic studies in patients with skin cancer have demonstrated the importance of exposure to ultraviolet and x-ray irradiation. This paper describes in vitro studies in peripheral lymphocytes from three patients with the nevoid basal cell carcinoma syndrome. Particular stress was placed on the following factors: (1) the distribution of the lymphocyte subsets, (2) the frequency of spontaneous sister chromatid exchange, (3) the effect of ultraviolet C (UVC) (254 nm) on deoxyribonucleic acid (DNA) synthesis, (4) the effect of UVC on the phytohemagglutinin-stimulated lymphocyte proliferation, and (5) the capacity to repair x-ray-induced DNA damage. Our data indicate that the distribution of the peripheral lymphocytes was normal, while the frequency of spontaneous sister chromatid exchange was high. The capacity of the lymphocytes to repair x-ray-induced DNA damage was low in all three patients. In two patients the UVC-induced DNA synthesis was reduced, while an increased UVC-induced inhibition of lymphocyte proliferation was observed. These cellular responses in vitro to ultraviolet and x-ray irradiation correspond to the clinical features of the nevoid basal cell carcinoma syndrome. A clearly defective in vitro cellular response to x-ray irradiation, reflecting the clinically evident x-ray sensitivity in the nevoid basal cell carcinoma syndrome, has not been reported previously.

Adult↗
PubMed1986

Flow cytometric discrimination of mitotic cells: resolution of M, as well as G1, S, and G2 phase nuclei with mithramycin, propidium iodide, and ethidium bromide after fixation with formaldehyde.

Cells in mitosis can be flow cytometrically discriminated from G1, S, and G2 cells by analysis of a nuclear suspension prepared with nonionic detergent, fixed with formaldehyde, and stained with mithramycin, propidium iodide, or ethidium bromide. With these DNA-fluorochromes, the fluorescence is quenched by formaldehyde less in mitotic nuclei than in interphase nuclei. Mitotic nuclei have a 20-40% increased mithramycin fluorescence and 30-60% decreased light scatter in comparison to those of G2 nuclei. There is a high correlation (r = 0.95; P less than 0.001) between microscope counts of mitotic figures in smear preparations of the initial cell suspension and the flow cytometrically estimated fraction of nuclei with increased mithramycin fluorescence. Flow sorting (FACS) demonstrates that the mitotic nuclei are confined to the peak of increased mithramycin fluorescence and decreased light scatter. The method has been applied to cultures of Yoshida ascites tumor cells, JB-1 reticulosarcoma cells, and PHA-stimulated human lymphocytes, incubated in the presence or absence of vinblastine for mitotic arrest. In a heteroploid mixture of fixed Yoshida (near-diploid) and JB-1 (hypotetraploid) nuclei, the mitotic fractions of the two cell lines could be estimated separately when analyzed with mithramycin fluorescence versus light scatter or with mithramycin fluorescence versus propidium iodide fluorescence.

Animals↗
PubMed1986

Thymidine kinase isoenzymes in human acute and chronic lymphatic leukemia.

The dominating thymidine kinase isoenzyme was examined in mononuclear leucocytes from two patients, one with acute and one with chronic lymphatic leukemia. The two isoenzymes exhibited Michaelis-Menten substrate kinetics with ATP and cooperative inhibition kinetics with dTTP. The substrate kinetics with thymidine were different. According to the enzymatic properties the isoenzymes from the acute and chronic lymphatic cells were designated TK 3 and TK 4, respectively. Comparison with the isoenzymes in normal lymphocytes (TK 1, TK 2) and in acute monocytic leukemic cells (TK 3, TK 4) indicated the existence of three thymidine kinase isoenzymes in human leukemic cells which differed from the two isoenzymes in normal human lymphocytes.

Adenosine Triphosphate↗
PubMed1986

Non-replicative DNA synthesis detected in peripheral lymphocytes from a patient with actinic reticuloid.

A patient with actinic reticuloid has been followed with repeated investigations on DNA synthesis and immunology in blood lymphocytes. The spontaneous DNA synthesis of the patient's lymphocytes was increased to a level not previously recognized. Especially high values were observed at times when the patient was erythrodermic. The increased DNA synthesis cannot be explained by the presence of an increased number of mitotically cycling cells in the patient's blood. Normal subpopulations in blood lymphocytes were found by immunological investigations.

Aged↗
PubMed1985

Thymidine kinase isoenzymes in human acute monocytic leukemia.

Two thymidine kinase isoenzymes, TK 3 and TK 4, from mononuclear leucocytes from a patient with acute monocytic leukemia, were purified and characterized in regard to the molecular weights and kinetic properties. The molecular weights of TK 3 and TK 4 were 60 000 and 45 000, respectively. In the presence of 2 mM ATP, the molecular weight of TK 3 increased to 200 000, whereas the molecular weight of TK 4 was unchanged. Studies of the kinetic properties showed clear differences between TK 3 and TK 4. With thymidine as substrate, TK 3 showed biphasic kinetics with a Km of 22 microM, and TK 4 showed Michaelis-Menten kinetics with a Km of 0.33 microM. With ATP as substrate, TK 3 showed Michaelis-Menten kinetics with a Km of 100 microM, and TK 4 showed biphasic kinetics with a Km of 3.5 microM. With dTTP as inhibitor, TK 3 showed cooperative inhibition kinetics, and TK 4 showed non-cooperative competitive inhibition kinetics. The dTTP concentration at 50% inhibition was 75 microM for TK 3 but 380 microM for TK 4. Comparison of the molecular weights and the kinetic properties of TK 3 and TK 4 with the corresponding data previously obtained for TK 1 and TK 2 from normal human lymphocytes indicate the existence of four thymidine kinase isoenzymes in human leucocytes.

Chromatography, Ion Exchange↗
PubMed1985

Abnormal lymphocyte response to u.v. radiation in multiple skin cancer.

The lymphocyte response to u.v. radiation (254 nm) was investigated by two different methods in 29 unselected patients with multiple epidermal cancer. The u.v.-induced DNA synthesis was determined as the increase in incorporation of [3H]thymidine in irradiated cells compared with nonirradiated cells after incubation for 2 h. The u.v. tolerance was measured as the u.v. dose necessary for 50% reduction in phytohemagglutinin-stimulated lymphocyte proliferation. Patients with both squamous cell differentiated tumors and basal cell carcinomas had very high u.v.-induced DNA synthesis values (p less than 0.01, when compared with patients with basal cell carcinoma only and p less than 0.005, when compared with controls). The u.v. tolerance in patient lymphocytes was considerably lower than in control lymphocytes (p less than 0.001), with the lowest values occurring in patients with clinical sun intolerance (p = 0.05, when compared with the remaining patients). These investigations may be of predictive value in skin carcinogenesis.

Adult↗
PubMed1985

Seasonal variations in UVR-induced DNA synthesis and in UVR inhibition of phytohaemagglutinin-stimulated proliferation of human lymphocytes.

Two years of sequential studies of the UVR (254 nm) response in normal human lymphocytes showed pronounced seasonal variations. In the winters of 1981-82 and 1982-83 the UVR-induced DNA synthesis in the lymphocytes in vitro (the DNA-repair synthesis) was very stable with inter- and intra-individual variations below 14 and 10%, respectively (15 individuals). In the summers 1982 and 1983 the inter-individual variations was 2-3-fold higher. Closer analysis revealed that this was due to a pronounced intra-individual variation with sharp fluctuations in the single individual. Also the UVR tolerance of the lymphocytes estimated by alterations of the phytohaemagglutinin (PHA) stimulated lymphocyte proliferation showed seasonal variations, being 1.5-fold higher in the winter than in the summer (P less than 0.0001, 12 individuals). The observed seasonal variations emphasize the importance of considering chronobiological variations when working with long term projects. The UVR-induced DNA synthesis was determined as the increase in incorporation of [3H]-thymidine in irradiated cells compared to non-irradiated cells after incubation for 2 h at 37 degrees C in phosphate buffered saline. The UVR tolerance was measured by the UV dose necessary for 50% reduction in PHA stimulated lymphocyte proliferation assessed after 7 days of growth.

Adult↗
PubMed1985

X-ray and UV-radiation sensitivity of circulating lymphocytes in multiple epidermal cancer in relation to previous radiation exposure.

The cellular sensitivity to X rays (200 kV, 16 mA) and UV radiation (254 nm) was examined in lymphocytes from three groups of patients with multiple epidermal malignant tumors, selected by their clinical history of carcinogenesis. Eight patients previously exposed to low energy ionizing radiation (less than or equal to 12 kV) had an increased cellular sensitivity to UV radiation as well as X rays compared with 24 age and sex matched controls. This indicates the existence of a cellular cross-sensitivity to UV radiation and ionizing radiation not previously established for human cells. In contrast six patients previously exposed to high energy ionizing radiation (between 25 and 170 kV) had normal cellular response to both UV radiation and X rays, indicating a different biologic effect of low and high energy ionizing radiation. In the third group of patients, previously exposed to therapeutic UV radiation/excess sunlight, the lymphocytes had a normal response to X rays, but an increased sensitivity to UV radiation. The possibility of evaluating the individual risk at radiation exposure is suggested.

Adult↗
PubMed1984

An unusual case of multiple malignancy in an adult.

An adult female is described who, during a clinical course of 25 years, presented malignant tumors of the rectum, breast, uterus and colon. Cytostatics were never administered. Lymphocyte subsets, a variety of lymphocyte and mononuclear cell stimulation assays with mitogens and antigens, DNA repair tests and activity of natural killer cells were normal. Serum leukocytic interleukin-1 activity was slightly elevated. Sister chromatid exchange frequency in peripheral lymphocytes was below the normal range. An explanation for the development of 4 primary malignant neoplasms was not found.

Breast Neoplasms↗
PubMed1984

Differences in the kinetic properties of thymidine kinase isoenzymes in unstimulated and phytohemagglutinin-stimulated human lymphocytes.

The two thymidine kinases, TK 1 and TK 2, found in phytohemagglutinin-stimulated human lymphocytes and the thymidine kinase, TK 2N, found in unstimulated human lymphocytes were purified and characterized. All three kinases had molecular weights between 70 000 and 75 000 which increased to 170 000-200 000 in the presence of 2 mM ATP. Studies on the kinetic properties of the enzymes with thymidine and ATP as the substrates and dTTP as the inhibitor showed clear differences between TK 1 and TK 2, but a close similarity between TK 2 and TK 2N. With thymidine as the variable substrate, TK 1 showed Michaelis-Menten kinetics, whereas TK 2 and TK 2N showed characteristic biphasic kinetics. With ATP as the variable substrate, all three enzymes showed positive cooperative kinetics, but TK 2 and TK 2N lost the cooperativity in the presence of dTTP. The results from inhibition studies showed, that dTTP was a cooperative inhibitor of TK 1 but a non-cooperative inhibitor of TK 2 and TK 2N.

Humans↗
PubMed1977

Induction of thymidine kinases in phytohaemagglutinin-stimulated human lymphocytes.

Thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) activity increased approx. 200-fold during transformation of human lymphocytes with phytohaemagglutinin. Two peaks of thymidine kinase (peak IS and peak IIS) were separated from stimulated lymphocytes on DEAE-Sephadex. The activity in peak IS was 20-fold the activity in peak IIS. Only one peak was obtained from normal lymphocytes (peak IIN). The elution volume of this peak was identical to that of peak IIS. The Km values for ATP were 1 mM for peak IS, 0.2 mM for peak IIS and 0.3 mM for peak IIN. 90 micronM dTTP gave 50% inhibition of the activity in peak IS, while the same inhibition of the activities in peak IIS and peak IIN was obtained with only 15 micronM dTTP. Km for thymidine was about 6 micronM for peak IS. The kinetic relation between thymidine and the activity in peak IIS was complex but very similar to that of peak IIN. It is suggested, that a new form of thymidine kinase appears in the lymphocytes due to phytohaemagglutinin stimulation.

Computers↗