[Devic's syndrome (neuromyelitis optica) in the course of infiltrative pulmonary tuberculosis].
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Biomedical subjects
Publications and source records attributed to S Mazurek.
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A strong and coordinated upregulation of the glycolytic, glutaminolytic and pentose phosphate pathway enzymes occurs during the onset of lactation in the normal mouse mammary gland. Induction of apoptosis by removing the pups led to an inactivation of the same enzymes with different time courses. While the ATP-consuming glycolytic 6-phosphofructo 1-kinase and mitochondrial bound hexokinase still remained high on days one and two of involution, the ATP-regenerating pyruvate kinase was immediately reduced. The enzymes of the pentose phosphate and glutaminolytic pathway were inactivated on the first two days of involution. In accordance with such an inactivation of the enzymes ATP, GTP, UTP, ADP, NAD NADH and lactate concentrations decreased. The synthetic product of UTP, UDP-N-acetylglucosamine, increased. AMP was found in the milk, not in the epithelial cells. The inactivation of the enzymes was caused by partial proteolysis or by a loss of the intact proteins from the cytosol without signs of proteolysis.
The pyruvate kinase isoenzyme M2-PK is known to be associated with a metabolic shift that is characteristic for tumor cells. Meanwhile, the universal expression of this isoenzyme is the basis for the detection of various tumor diseases in human clinical diagnosis. Other enzymes which are known to be essential for this tumor specific metabolic shift in rat chemical carcinogenesis are the NADP-dependent enzymes malic enzyme, isocitrate dehydrogenase and glucose 6-phosphate dehydrogenase. To evaluate the role of these enzymes in human carcinogenesis, we compared their enzymatic activities in normal colon mucosa and tissues derived from primary colon tumors. Histochemical staining showed that the enzyme activities were restricted to mucosal colon cells and colon cancer cells. The enzymes were strongly but heterogeneously expressed in the tumor tissues, whereas staining of normal mucosa was weak. Tumor M2-PK showed the most prominent differences in normal colon mucosa and colon cancer cells.
INTRODUCTION: Tyrosine kinase signal transduction pathways are a focus of interest for therapeutic interventions. The oncoprotein HER-2/neu shows tyrosine kinase activity leading to phosphorylation and activation of numerous second-messenger systems. One target of phosphorylation processes is assumed to be the tumor type M2 isoenzyme of pyruvate kinase (TuM2-PK) which has been shown to be elevated in metastatic breast cancer. MATERIALS AND METHODS: We measured the plasma levels of HER-2/neu, TuM2-PK and tyrosine-phosphorylated TuM2-PK (p-TuM2-PK) in 69 patients (pts) with breast cancer and correlated these parameters to each other and to the classical tumor marker CA 27.29. The samples were measured with ELISA assays while CA 27.29 was determined with an automated chemiluminescence assay. For analysis, we formed 5 subgroups according to the plasma HER-2/neu levels (group 1: < 15 ng/ml, n = 28; group 2: 15 < or = x < 50 ng/ml, n = 21; group 3: 50 < or = x < 100 ng/ml, n = 9; group 4: 100 < or = x < 500 ng/ml, n = 7; group 5: > or = 500 ng/ml, n = 4). RESULTS: From the HER-2/neu group 1 to group 5, there was a statistically significant increase of CA 27.29 from 35.8 U/ml to 1095.8 U/ml (p < 0.001). There was also a trend for increasing TuM2-PK levels with increasing HER-2/neu levels (p = 0.126). From the lowest extinction (0.088) to the highest extinction result (2.167) of p-TuM2-PK we found a 25-fold increase, which was reproducible in spiking and dilution experiments proving that TuM2-PK is phosphorylated at tyrosine residues to a certain extent. However, there was no correlation between plasma HER-2/neu and p-TuM2-PK levels. CONCLUSION: TuM2-PK is phosphorylated at tyrosine residues in breast cancer patients. Using the shed antigen of HER-2/neu in plasma as a surrogate marker, we did not find any evidence that this phosphorylation is initiated by the oncoprotein HER-2/neu.
The study aimed at evaluating a possible relationship between the adrenergic system tone determined with the excretion of catecholamines with the urine and an incidence of the ventricular arrhythmias in patients with the mitral valve prolapse. The study included 20 patients (13 women and 7 men aged between 20 and 50 years; mean = 31.6 years) with the mitral valve prolapse syndrome diagnosed with the aid of the patients' history, physical examinations and echocardiography. Echocardiograms have shown anterior mitral leaflet prolapse in 7 patients, posterior mitral leaflet prolapse in 8 patients, and both mitral leaflets prolapse in the remaining 5 patients. Daily excretion of adrenaline and noradrenaline was measured with Van Euler and Lishajko's fluorimetric technique. Cardiac arrhythmias were determined with a 24-hour ECG monitoring and classified according to Lown. Premature ventricular contractions of class I were seen in 1 patient, of class II in 5, class III in 1, class IV in 2, and class V in 3 patients. Holter monitoring technique did not show the arrhythmias in 8 patients. Daily adrenaline and noradrenaline excretion with the urine was within the normal values (3.2-30.8 ug and 0.2-16.2 ug, respectively) in all examined patients. Daily urine noradrenaline was higher in patients with serious ventricular arrhythmias (Lown's class V) than mean values in the whole examined group.
Proliferating and tumor cells express a certain isoenzyme of pyruvate kinase, called PK type M2. This isoenzyme can be isolated in an active tetrameric and an inactive dimeric form. We have termed this form tumor type M2-PK. This tumor type pyruvate kinase can be quantified by a specific ELISA in blood sera and tumor homogenates. In this study we have compared 26 normal colon mucosa and colon cancer specimens from the same patients. The total specific pyruvate kinase activity and the amount of the tumour type M2-PK measured by ELISA was increased in the tumor samples compared to the normal colon mucosa of the same patient. In normal colon mucosa the specific PK-activity ranged between 0.21 and 1.25 U/mg protein whereas in colon carcinoma we found activities between 0.99 and 7.08 U/mg. The amount of tumor M2-PK measured by ELISA ranged between 0.82 and 27.10 U/mg protein in normal colon mucosa and between 1.96 and 242.40 U/mg protein in colon carcinoma. The tumor M2-PK content in the serum of 666 healthy blood donors was measured by ELISA and compared to sera from 15 colon carcinoma patients and showed a highly significant difference (Mann-Whitney rank sum test, p < 0.001). The values for the 50%-percentiles (median) of blood donors were 10.8 U/ml and 55.0 U/ml for colon carcinoma.
The interaction between glycolysis, glutaminolysis and tumor growth in WAG/Fra rnu/rnu rats has been investigated. Small tumors are characterized by a low conversion of glucose to lactate whereas the conversion of glutamine to lactate is high. In medium sized tumors the flow of glucose to lactate as well as oxygen utilization are increased whereas glutamine and serine consumption are reduced. At this stage the tumor cells start with glutamate and alanine production. Large tumors are characterized by a low oxygen and glucose supply but a high glucose and oxygen utilization rate. The conversion of glucose to glycine, alanine, glutamate, glutamine, and proline reaches high values and the amino acids are released. Pyruvate kinase increases with tumor weight and is positively correlated with an increase in glucose and oxygen utilization. The shift from glutamate consumption to glutamate production is correlated with an increase in glutamate dehydrogenase and glutamate oxaloacetate transaminase activity.
Extracellular AMP inhibits cell proliferation of MCF-7 and MDA-MB-453 whereas cell proliferation of the highly malignant Novikoff cell line is not affected. In medium with low glucose supply MDA-MB-453 cells grow well, Novikoff cells are slightly inhibited and MCF-7 cells are totally unable to grow. Isoelectric focusing revealed that a glyclytic enzyme complex exists in all three cell lines. In addition to the glycolytic enzymes, c-Raf-kinase, adenylate kinase, and nucleoside diphosphate kinase are also found within the complex. The differences in glucose in dependence of the three cell lines can be explained by the different constitutions of shuttle enzymes. MDA-MB-453 and Novikoff cells contain cytsolic glycerol 3-phosphate dehydrogenase which is associated with glyceraldehyde 3-phosphate dehydrogenase within the glycolytic enzyme complex and which is responsible for the transport of cytoslic hydrogen in the mitochondria. MCF-7 and Novikoff cells contain the pI 7.8 form of malate dehydrogenase which couples glycolysis with glutaminolysis.