Biomedical subjects
Publications and source records attributed to M Szmitkowski.
The paper presents the new aspects of structure and kinetics of alcohol dehydrogenase. The differences in substrate specificity of isoenzymes are broadly discussed. The newly discovered gastric alcohol dehydrogenase is also mentioned.
We examined the activity of class I and II of alcohol dehydrogenase isoenzymes in the sera of patients with viral hepatitis using fluorogenic substrates, 4-methoxy-1-naphthaldehyde for class I and 6-methoxy-2-naphthaldehyde for class II. It was found that serum activities of class I and II of alcohol dehydrogenase isoenzymes during five weeks of hospitalisation were higher than that of control. The greatest increase in activities was found at the onset of disease, and exceeded the mean control value about 30 times for class I and 4 times for class II. These were lower than the aminotransferase activities but higher than the activity of lactate dehydrogenase, alkaline phosphatase and gamma-glutamyltransferase. In the following periods of investigation the activity of alcohol dehydrogenase isoenzymes gradually decreased, but did not reach the values of the control groups in the last period of the study. Activity of class I and II of alcohol dehydrogenase isoenzymes showed a good correlation with alanine and aspartate aminotransferase and lactate dehydrogenase in the first weeks of the illness. These results clearly demonstrate that particularly the activity of class I of alcohol dehydrogenase isoenzymes measured by a fluorimetric method can be a useful marker of liver cell damage in the course of viral hepatitis.
Assessment of beta-2-microglobulin (beta-2-M) concentration in serum and urine was made in 50 patients with rheumatoid arthritis (RA). The most often noticed pathology was proteinuria. We observed a significant increase of beta-2-M concentration in serum of patients without rheumatoid factor and in patients with proteinuria. In all patients the concentration of beta-2-M in urine was significantly higher than in the controls. We did not observe any influence after treatment on beta-2-M concentration. The increase of the concentration of beta-2-M may be a marker for the early damage of kidney in RA.
We examined the activities of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with viral hepatitis using the fluorogenic substrates 4-methoxy-1-naphthaldehyde for class I and 6-methoxy-2-naphthaldehyde for class II. It was found that serum activities of class I and II alcohol dehydrogenase isoenzymes over the course of five weeks of hospitalisation were higher than those of controls. The greatest increase in activities was found at the onset of disease, exceeding the mean control value by about 30 fold for class I and 4 fold for class II. These activities were lower than that of aminotransferase but higher than those for lactate dehydrogenase, alkaline phosphatase and gamma-glutamyltransferase. Thereafter, the activity of alcohol dehydrogenase isoenzymes gradually decreased, but did not reach the values of the control groups in the last period of the study. Activities of class I and II alcohol dehydrogenase isoenzymes correlated well with those of alanine and aspartate aminotransferase and lactate dehydrogenase in the first weeks of illness. These results clearly demonstrate that especially the activity of class I alcohol dehydrogenase isoenzyme measured by a fluorimetric method can be a useful marker of liver cell damage in the course of viral hepatitis.
Hematopoietic growth factors belong to the family of glycoproteins responsible for regulation, differentiation and proliferation of myelopoietic cells. In this paper the role of these factors in regulation of the function of phagocytic cells (granulocyte, monocyte, macrophage) is discussed on the basis of literature data.
Endotoxin concentrations were measured in the portal, hepatic venous blood and abdominal aorta of six groups of rats in experimental alcoholic liver injury. Groups of animal consisted of 16 rats: I.: control group; II.: rats received one dose of E. coli 0127: B8-3 mg/kg intraperitoneally (i.p.), III.: rats received three doses of E. coli; IV.: rats intoxicated with 20% ethanol ad libitum (60 days); V.: rats intoxicated with one dose of endotoxin after 20% ethanol ingestion; VI.: animal intoxicated with 20% ethanol and three doses of E. coli 0127: B8. The highest levels of endotoxin (determined by Limulus Lysate test) were in portal venous blood--3.1 pg/ml in control group to 113.4 pg/ml in VI. group. The level of endotoxin in plasma hepatic venous blood was elevated from 0.0 pg/ml (I., II. groups) to 15.8 pg/ml (III.), 34.3 pg/ml (IV.), 49.7 pg/ml (V.) up to 75.1 pg/ml (VI.). Plasma endotoxin concentration in abdominal aorta was highest in group VI.--32.2 pg/ml. The percentage of excretion rate of endotoxin by liver function was measured on the basis of difference between plasma endotoxin levels in the prehepatic blood (portal vein) and posthepatic blood (hepatic vein). The highest activity of biochemical parameters indicating liver injury was observed in animals intoxicated with ethanol and endotoxin.
The activity of class I and II alcohol dehydrogenases in the sera of alcoholics was estimated using specific and highly sensitive fluorogenic substrates. It was found that serum class I activity was increased about 2 fold above that of the control group. No such increase was observed in the activity of class II, and we did not find a significant difference in non-alcoholics. The total alcohol dehydrogenase activity measured by classical spectrophotometric methods at pH 9.2 confirmed the increase of class I alcohol dehydrogenase. Additionally, the activity of liver injury markers were detected. Only gamma-glutamyltransferase activity exceeded the normal range. Based on the results of the present study, we would suggest that the significant elevated serum activity of class I alcohol dehydrogenase may be derived not from liver cells, because they did not display the obvious enzymatic markers, but from different organs, especially the gastrointestinal tract. The tissue distribution of alcohol dehydrogenase isoenzymes and gamma-glutamyltransferase would help to confirm this possibility.
Serum alcohol dehydrogenase activity at different pH-values (8.8, 9.6 and 10.4) was investigated in induced endotoxemia (3 mg/kg) after chronic alcohol consumption in rats (60 days, 11.5 mg/kg, per day). It has been shown that ADH activity is higher after the single than after the triple injection of endotoxin given the healthy rats. Such a difference was not observed in the ethanol-intoxicated rats. The single dose of endotoxin did not maintain the increased ADH activity after alcohol administration, however a triple injection of endotoxin maintained the activity but did not increase. This results show, that the highest ADH activity in all tested rats was observed at pH 9.6 and that chronic ethanol consumption did not cause an increase of the toxic effects of endotoxin on liver cells, measured by serum alcohol dehydrogenase activity.
The paper presents the molecular and kinetics aspects of alcohol dehydrogenase polymorphism. The role of this enzyme in ethanol metabolism are too discussed.
The morphological and biochemical changes of the liver after endotoxin intake were analyzed in rats receiving 20% ethanol during 60 days. Besides morphological changes, concentration of serotonin and histamine in liver homogenates, the activity of asparagine and alanine aminotransferases (AspAT, ALAT), gamma-glutamyltranspeptidase (GGTP) and alcohol dehydrogenase (ADH) in blood serum were determined, too. The most extensive morphologic changes of the liver were seen in group of animals intoxicated with 20% ethanol during 60 days and single dose of endotoxin E. coli 0127:B8 intraperitoneally. These changes included necrosis most hepatocytes, focal steatosis of liver parenchyma, considerable hyperemia and parenchymatous degeneration of the liver cells. The cells lining liver sinuses showed considerable swelling as well as necrotic changes. Figures of cell division and haemorrhagic focuses were seen, too. The clusters of mononuclear cells, surrounding necrotically changed hepatocytes were seen in the central part of the liver lobule. Among the inflammatory mediators estimated in liver homogenate only serotonin reached a high level in the group of experimental animals receiving only endotoxin. Increased activity of aminotransferases AspAt and ALAT were associated with these morphologic and biochemical changes in liver tissue observed in animals receiving ethanol and endotoxin.
Stem cell factor (SCF) is the ligand for the receptor encoded by the c-kit proto-oncogene. Mutations of either c-kit or the SCF gene are responsible for the defects of W and SI mutant mice, which both suffer a macrocytic anemia, the former associated with defective stem cells and the latter with a defective hematopoietic microenvironment. PEGylated recombinant rat SCF was administered to normal or splenectomized mice for up to 21 days. SCF was found to be a modest stimulator of peripheral blood neutrophil numbers in both groups of animals. The peak in neutrophil numbers was higher and occurred earlier in splenectomized mice. Bone marrow and spleen cellularity changed little during treatment but the content of interleukin-3-responsive progenitor cells and spleen colony-forming cells (CFU-S) reached very high levels, particularly in the spleen. Using recombinant human granulocyte colony-stimulating factor (rhG-CSF), we have shown that SCF induces a greater than additive increase in both blood neutrophils and blood-borne CFU-S. This synergy was seen throughout the dose range and may indicate a clinical role for SCF either alone or in augmenting the activity of G-CSF upon blood neutrophils and transplantable stem cells.
Cord blood triglyceride concentration increased in cases of placental insufficiency. The significant relationship has been found between elevated triglyceride, decreased Apgar score, and low pH values. We suggest that the measurement of cord blood triglyceridemia might be used as a valuable indicator of chronic fetal distress.
Influence of sera of children with ALL on character (dispersed or compact) and composition (granulocyte or macrophage) of colonies, formed from the human promyelocytic leukemia cell line HL-60, was estimated. An increased activities stimulating formation of dispersed G and M colonies was found in the sera of patients before therapy. Dynamics of colonies formation and their composition in the course of treatment point to some changes in the serum the levels of these activities with a tendency to full normalization in remission.
Serum alcohol dehydrogenase activity was estimated at pH 10.4 (optimum for the typical liver isoenzyme), 8.8 (optimum for atypical liver isoenzyme), at the physiological serum pH of 7.4, and at pH 9.2, with a view to obtaining the greatest possible difference between patients and controls. Measurements were performed on the sera of 39 children aged from 2 to 13 years, using the Technicon analyzer RA-1000 with the continuously measuring method of Bonnichsen & Brink. Blood sera were tested at the onset of viral hepatitis, in the first week of hospitalization, and three times thereafter at intervals of 7 to 9 days. During the illness, the activity of serum alcohol dehydrogenase, measured at different pH-values, was higher than that of controls. The ratio of activity at pH 10.4 to activity at pH 8.8 in the sera differed from that previously reported for liver cells. The highest increase in alcohol dehydrogenase activity was at pH 9.2. The diagnostic sensitivity of alcohol dehydrogenase determination at this pH is lower than that of alanine aminotransferase, gamma-glutamyltransferase and aspartate amino-transferase, but higher than that of lactate dehydrogenase, alkaline phosphatase and bilirubin; alcohol dehydrogenase activity also shows the best correlation with the activity of gamma-glutamyltransferase.
The effect of commercially available colony stimulating factors and mouse post-endotoxin serum on bactericidal activity and phagocytosis of bacteria by blood neutrophils was tested on mice in vivo after intraperitoneal injection. It was found that tested substances are able to induce phagocytosis and bactericidal activity of blood granulocytes. The similar patterns of these actions during 48 hours were observed for mouse IL-3 and human GM-CSF and for GCT-CM and post-endotoxin serum.
Treatment of rats with 10% ethanol for 6 months induced a 3-4-fold increase of [3H]proline incorporation into liver collagen and enhanced the level of prolyl hydroxylase activity in liver and serum of intoxicated rats. Several diagnostic tests used to assess liver disease failed to demonstrate any symptom of liver damage. Therefore, increased collagen biosynthesis appears to precede other symptoms of liver damage induced by ethanol.
The effect of different doses of endotoxin (Lipopolysaccharide B) on Granulocyte-Macrophage Colony Stimulating Activity (GM-CSA) in the sera of "Swiss" male mice was measured by granulocyte-macrophage "in vitro" colony formation. The highest GM-CSA was found to be present 3-4 hours after 200 micrograms of endotoxin intraperitoneal injection.
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