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Biomedical subjects

J Michalowski

Publications and source records attributed to J Michalowski.

At least 19 recordsLinked to original sources
PubMed2001

Defects in transcription coupled repair interfere with expression of p90(MDM2) in response to ultraviolet light.

Ultraviolet (UV) irradiation transiently stabilizes p53 through a mechanism that may require a decrease in the activity of the ubiquitin ligase, p90(MDM2). Conversely, the recovery of low levels of p53 following UV exposure may depend on an increase in p90(MDM2). The level of p90(MDM2) is increased by UV light following the p53-dependent induction of an internal mdm2 promoter, P2. If this induction of mdm2 were critical for the recovery of low levels of p53 following UV exposure, defects in mdm2's transcription would result in a prolonged increase in p53. Cells defective in transcription coupled repair (TCR) maintain high levels of p53 for a prolonged period following UV exposure. Such cells also have defects in general transcription after UV irradiation. We investigated whether TCR-deficient cells express diminished levels of mdm2 mRNA and p90(MDM2) following UV exposure. We found that transcription of mdm2 was reduced in TCR-deficient cells. The uninducible mdm2 promoter, P1, was more sensitive to the inhibitory effects of UV irradiation than the P2 promoter. The decrease in transcription from the P1 promoter was sufficient to reduce the level of p90(MDM2) and correlated with a prolonged increase in p53. Thus, p53-independent transcription of mdm2 appears critical to p53's regulation.

DNA Damage↗
PubMed1998

Development of solid-phase chemiluminescence immunoassays for digoxin comparing flow injection and sequential injection techniques.

The development of a competitive solid-phase immunoassay for digoxin making use of the acridinium chemiluminescence system is described. Two different instrumental approaches are compared. One is based on a continuous flow system using a peristaltic flow injection analysis pump; the other uses a new sequential injection technique. In both systems a flow cell, consisting of transparent PTFE tubing packed with immobilized antibodies, acts as an immunoreactor. The entire assay, including both the immunoreaction and the chemiluminescence reaction, takes place in this immunoreactor cell. Compared with the flow injection technique, the sequential injection mode showed higher precision, ranging from 2.16 to 5.5% RSD depending on concentration. The total assay time, including regeneration, is less than 8 min with the sequential injection technique. The detection limit for both techniques is in the low femtomole range.

Cardiotonic Agents↗
PubMed1988

Prostacyclin and regional coronary blood flow in experimental myocardial infarction.

Infusion of prostacyclin (PGI2) has been reported to affect infarct size and myocardial blood flow favourably in various animal models of myocardial ischaemia. Recent data suggest that a similar effect of PGI2 may occur also in humans with acute myocardial infarction. We addressed the hypothesis that PGI2 redistributes myocardial blood flow following coronary ligation, and that this effect favours perfusion of myocardium at risk and thereby limits infarct size. Following ligation of a distal branch of the left coronary artery in anaesthetized dogs, PGI2 (2-4 ng/kg/min) was infused for 72 h. Regional myocardial blood flow was assessed immediately after the coronary ligation and at the end of the drug infusion, by injection of 57Co- and 113Sn-labelled microspheres, respectively. Coronary ligation reduced regional coronary blood flow by 40-70%. During the subsequent 72 h the blood flow increased, being at the end of the period 50-70% of the flow in the non-ischaemic myocardium. PGI2 did not affect the spontaneous improvement of regional myocardial blood flow, as assessed at the end of the infusion. PGI2 also failed to affect infarct size, either when expressed in relation to total left ventricular mass, or in relation to area at risk. We conclude that PGI2, when infused immediately after coronary ligation in dogs in a clinically relevant dose, neither affects regional myocardial blood flow in the ischaemic regions, nor the size of the myocardial infarction.

Animals↗
PubMed1978

Inhibition of the RNA dependent DNA polymerase and the malignant transforming ability of Rous sarcoma virus by thiosemicarbazone-transition metal complexes.

Several thiosemicarbazone-metal complexes inhibit the RNA dependent DNA polymerase and the transforming ability of Rous sarcoma virus. Some complexes are equally as active as the free ligand whereas the activity of others is greatly enhanced. The 2-formyl pyridine thiosemicarbazone copper (II) complex is the most potent compound of this class that we tested. Some copper complexes of salicylaldehyde derivatives are very active also, particularly N-n-butyl, N-n-hexyl and N-benzylsalicylaldimine; no nickel complex of any salicylaldehyde compound is active. In addition, other metal ligands, such as dithizone, diacetyl bis (mercaptoethylimine), N-butyl thiocarbamate, 0,0' dimethyl dithiophosphate, potassium dithiooxalate, and cis-PtII(NH3)2Cl2 were tested with varying results.

Aldehydes↗
PubMed1977

Motility- and blood flow-dependent absorption of amino acids in canine small intestine.

A relationship between L-phenylalanine and L-serine absorption, intestinal motility and blood flow has been studied with a canine in situ isolated jejunal loop in acute experiments and in chronic preparations in conscious dogs. During spontaneous rhythmic contractions, as well as after mechanical and pharmacological stimuli, rhythmic changes in blood flow, related to intestinal contractions, were observed. They had no bearing on mean blood flow or absorption as long as they did not occur together with tonic contractions. The tonic contractions resulted in a prolonged decrease in jejunal blood flow ano diminished amino acid absorption rate. Absorption and motility index, as well as blood flow and motility were negatively correlated. There was a positive rectlinear correlation between intestinal blood flow and absorption, regardless of whether changes in blood flow resulted from the increase in motility or were induced by intestinal artery occlusion. These correlations suggest that changes in amino acid absorption during increased motility depend on changes in blood flow. This relationship may be important in clinical syndromes with hypermotility.

Amino Acids↗