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Biomedical subjects

M Gajewski

Publications and source records attributed to M Gajewski.

At least 19 recordsLinked to original sources
PubMed2001

Electrospray tandem mass spectrometry of lexitropsins.

Several compounds, representative of the class of lexitropsins, were analyzed by electrospray tandem mass spectrometry. The study of the fragmentations of the protonated molecular species ([M + H](+)) and of selected fragment ions allowed proposals for the main fragmentation pathways of compounds of this type. The interpretation of the fragmentation pathways of these compounds was complicated because of intramolecular hydrogen migration. In order to better understand the fragmentation pathways, the MS/MS/MS spectra of several compounds, and the MS/MS and MS/MS/MS spectra of the deuterated compounds, were obtained. Accurate mass measurements helped elucidate the structures of smaller fragment ions. Low-energy collision-induced decomposition (CID) tandem mass spectrometry of lexitropsins with electrospray ionization has proven to be a good method for the structural characterization and identification of this class of compounds. Main fragmentation pathways occur by cleavage of the peptide bond followed by the elimination of the substituted pyrrole ring, and their elucidation will facilitate structural characterization of new lexitropsins.

Antineoplastic Agents↗
PubMed2001

Homologues of c-hairy1 (her9) and lunatic fringe in zebrafish are expressed in the developing central nervous system, but not in the presomitic mesoderm.

A number of genes that are involved in somitogenesis in vertebrates are cyclically expressed in the presomitic mesoderm. These include homologues of the Drosophila genes fringe and hairy. We have analysed here two genes that belong to these classes in the zebrafish, namely the apparent orthologues of lunatic fringe (l-fng) and of c-hairy1 (called her9). However, unlike the respective mouse and chicken genes, they are not expressed cyclically in the presomitic mesoderm. Instead, both genes are mainly expressed in the central nervous system. her9 is predominantly expressed in the fore- and midbrain, and transiently in the hindbrain. Thus, the previously identified and only very distantly related her1 gene of zebrafish has more similarities to the expression of the c-hairy1 gene than its apparent orthologue her9, indicating that sequence similarity and similarity of function are not necessarily linked in this case. l-fng expression is found in alternating pre-rhombomeres, comparable to the equivalent mouse gene expression and in the anterior compartments of the mature somites, which was also shown for the chicken l-fng gene. The latter expression indicates that it might be involved in boundary definition and cell fate decision processes, rather than in pre-patterning of the somites. Interestingly, a similar role has previously been inferred for the grasshopper homologue of l-fng. This suggests that the function of l-fng in boundary definition of the somites might be ancestral, while its recruitment to the pre-patterning process of the somites might be a derived feature in higher vertebrates.

Amino Acid Sequence↗
PubMed1998

Some aspects of the inflammatory process.

The inflammatory process is a nonspecific complex, stereotype, coordinated response of tissues to injury. This process involves vascular permeability, active migration of blood cells, and passage of plasma constituents into the injurious tissue. The molecules that mediate the initial events of inflammation are the adhesion molecules. They are localized on leukocytes and endothelium. The adhesion and cell-cell cooperation appear to be critical for the migration of leukocytes to the abluminal surface of the blood vessels. The emigrating cells initiate the complex reactions that are controlled by a multitude of intercellular messengers called mediators. Prostanoids, that are products of arachidonic acid metabolism in cyclooxygenase pathway are involved in the process of communication between cells. Two isoforms of the cyclooxygenase COX-1 and COX-2 were found. They subserve different physiological function largely because of the striking differences in their tissue expression and regulation. A common feature of chronic inflammation is the persistence of a large number of leukocytes in the tissue; thus, their removal is important for the resolution of the inflammatory process. The mechanism by which they are removed includes the apoptotic recognition system. The new concepts regarding the therapy of the diseases concomitant with inflammatory reaction should include the inhibition of the appropriate isoform of cyclooxygenase and the regulation of apoptotic process in some cells.

Animals↗
PubMed1995

The neuromodulation aspects of ischaemic myocardium: the importance of cholinergic system.

The ability of the heart to increase contractility and heart rate is facilitated by postganglionic sympathetic nerve endings that terminate within myocardium. In fact, the heart is often regarded as an "adrenergic" organ because beta-adrenergic agonists are powerful stimulants of cardiac contractility. Muscarinic cholinergic receptors mediate parasympathetic control of heart function. A primary effects of the muscarinic stimulation are opposite to those of beta-adrenergic stimulation. The modulation of an adrenergic receptors stimulation in the heart by cholinergic agonists may be the major means by which the muscarinic agonists alter heart function. When the hypoxic myocytes were exposed to adrenaline, the responsiveness of the cardiac cells to muscarinic stimuli had significantly increased, and a simultaneous potent increase in the expression of muscarinic receptors was observed. These result support the hypothesis that in ischaemic/hypoxic myocardium the role of cholinergic system may be more important than previously assumed. In this review an attempt was made to summarize the physiological and biochemical interactions in an autonomic nervous system in an ischaemic myocardium. The evidences of a relationship between ischaemia and inflammation are discussed. The better knowledge of feasible interactions of neuromodulators of an autonomic nervous system with myocardial and inflammatory cells, should lead to the development of successful pharmacological strategies for the prevention of ischaemic injury.

Animals↗
PubMed1994

Are histamine H1 receptors involved in ischaemia/reperfusion injury in rat heart?

During ischaemia, there was no apparent change in malondialdehyde (MDA) content in rat myocardium. However, reoxygenation resulted in a significant increase in MDA content. The changes evoked by ischaemia and reoxygenation were significantly attenuated by addition of fenistil (histamine H1 receptor antagonist). Enzymatic antioxidant systems were not significantly modified in the different periods of ischaemia and after 30 min of reoxygenation. It is suggested, that maintenance of an adequate endogenous antioxidant reserve during ischaemia may be important in recovery upon reoxygenation.

Animals↗
PubMed1993

Enhanced responsiveness of rat cardiac myocytes to muscarinic cholinergic stimulation during chemically-induced hypoxia.

In contrast to adrenaline, exogenously administered cholinergic agonist, carbachol have very little effect on the contractility of rat cardiac myocytes, unless its contractile has been increased by adrenergic agonist. This interaction between the muscarinic and adrenergic pathways has been suggested to be the major means by which muscarinic agonist alters adrenergic function. When the cardiac myocytes were incubated in the medium contained the mitochondrial respiratory inhibitor potassium cyanide (chemically-induced hypoxia) the spontaneous contractility was ceased. The contractility partly recovered when the cells were exposed to adrenergicstimulation. We showed that during chemical hypoxia, in which cellular ATP is decreased (37% of control), the responsiveness of myocytes to muscarinic cholinergic stimulation significantly increase. Contraction of myocytes, stimulated by adrenaline was totally inhibited by 10(-4)M of carbachol in control cells and 5 x 10(-6)M of carbachol in cells with chemically-induced hypoxia. This increase in physiological response to muscarinic stimulation was associated with an increase of muscarinic receptors (630%). The results support the hypothesis that in ischaemic/hypoxic myocardium the role of cholinergic system may be more important than previously assumed.

Animals↗
PubMed1991

Increase in the expression of muscarinic cholinergic receptors in isolated, neonatal rat cardiac myocytes treated with potassium cyanide.

On treatment of rat cardiac myocytes with potassium cyanide, ATP content significantly and rapidly decreased in all experimental groups as compared to untreated cells. Contrary to that, the level of muscarinic cholinergic receptors increased significantly, depending on the cyanide concentration. Twenty four hours after removal of cyanide, myocytes exhibited normal levels of both the receptor expression and ATP content.

Adenosine Triphosphate↗
PubMed1991

Neutrophils-induced increase of adenosine triphosphate depletion in rat neonatal cardiac myocytes with impaired energy metabolism.

Isolated, cultured rat neonatal cardiac myocytes were placed in medium supplemented with mitochondrial respiratory inhibitor potassium cyanide which caused a rapid adenosine triphosphate (ATP) depletion. These myocytes with the impaired energy metabolism ("hypoxia-like state") were exposed to unstimulated human neutrophils. Effect of human neutrophils on the myocytes in the "hypoxia-like state" was quantified as a total change in the amount of ATP in cardiac cells. After 5 hours of incubation of neutrophils with the myocytes in the "hypoxia-like state" an additional decrease (of 50 per cent) in ATP content was observed. Since catalase (which destroys hydrogen peroxide) prevented the further decline in ATP level in the myocytes with impaired energy metabolism, it seem that hydrogen peroxide and possibly their products are responsible for this effect. These results suggest that unstimulated human neutrophils after activation by the contact with injured cardiac cells caused further decrease of ATP level in target cells.

Adenosine Triphosphate↗