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Biomedical subjects

J Pettersson

Publications and source records attributed to J Pettersson.

At least 37 records · Page 2Linked to original sources

Modulation of virulence factor expression by pathogen target cell contact.

Upon contact with the eukaryotic cell, Yersinia pseudotuberculosis increased the rate of transcription of virulence genes (yop), as determined by in situ monitoring of light emission from individual bacteria expressing luciferase under the control of the yopE promoter. The microbe-host interaction triggered export of LcrQ, a negative regulator of Yop expression, via the Yop-type III secretion system. The intracellular concentration of LcrQ was thereby lowered, resulting in increased expression of Yops. These results suggest a key role for the type III secretion system of pathogenic bacteria to coordinate secretion with expression of virulence factors after physical contact with the target cell.

Bacterial Adhesion↗

In vitro determination of toxicity, binding, retention, subcellular distribution and biological efficacy of the boron neutron capture agent DAC-1.

In boron neutron capture therapy (BNCT), 10B is delivered selectively to the tumour cells and the nuclide then forms high-LET radiation (4He2+ and 7Li3+) upon neutron capture. Today much research is focused on development of a variety of boron compounds aimed for BNCT. The compounds must be thoroughly analysed in preclinical tests regarding basic characteristics such as binding and subcellular distribution to enable accurate estimations of dose-modifying factors. DAC-1,2-[2-(3-amino-propyl)-1,2-dicarba-closo-dodecaboran (12)-1-yl-methoxy]- 1,3-propanediol was synthesized at our laboratories and the human colon carcinoma cells LS-174T were used as an in vitro model. The boron compound showed a remarkable intracellular accumulation, 20-100 times higher than the boron content in the culture medium, in cultured cells and was not removed by extensive washes. Approximately half of the boron taken up also remained within the cells for at least 4 days. The DAC-1 compound alone was not toxic at boron concentrations below 2.5 micrograms B/g. The intracellular distribution of the boron compound was investigated by subcellular fractionation experiments and low pH treatments. It is possible that DAC-1 binds to some intracellular molecules or to membranes connected with organelles in the cytoplasm or even to the inside of the outer cell membrane. Another possibility is that the compound, due to the somewhat lipophilic properties, is embedded in the membranes. Thermal neutron irradiations were carried out at the Brookhaven Medical Research Reactor (BMRR). At a survival level of 0.1, DAC-1 + thermal neutrons were about 10.5 times more effective in cell inactivation than the thermal neutrons alone. Monte Carlo calculations gave a mean value of the 10B-dependent specific energy, the dose, of 0.22 Gy. The total physical dose during irradiation of DAC-1-containing cells with a neutron fluence of 0.18 x 10(12) n/cm2 was 0.39 Gy. The dose-modifying factor, at survival level 0.1, when comparing irradiation with thermal neutrons with and without DAC-1 was 3.4, while the dose-modifying factor when comparing neutron irradiations of cells with DAC-1 and irradiation of the cells with 60Co-gamma was 7.3. The results are encouraging and in vivo tests of tissue distributions and tumour uptake should now be carried out.

Biological Availability↗

Magnetic orientation of snow buntings (Plectrophenax nivalis), a species breeding in the high Arctic: passage migration through temperate-zone areas

Orientation tests were conducted with snow buntings (Plectrophenax nivalis) exposed to artificially manipulated magnetic fields, during both spring and autumn migration. Experiments were run under clear sunset skies and under simulated complete overcast. The birds closely followed experimental shifts of the magnetic fields during both seasons regardless of whether they had access to celestial cues. Clear-sky tests in vertical magnetic fields resulted in a significant bimodal orientation, the directionality of which was almost identical during spring and autumn. When the snow buntings were deprived of celestial directional information and tested in vertical magnetic fields, they failed to show any statistically significant mean directions in either spring or autumn. The results demonstrate that snow buntings possess a magnetic compass and suggest that magnetic cues are of primary importance for their migratory orientation while on passage through temperate-zone areas. However, the axial orientation in vertical magnetic fields under clear skies may indicate an involvement of celestial cues as an auxiliary source of directional information.

Journal Article↗

Increased sensitivity for the diagnosis of healed myocardial infarction using vectorial information in the 12-lead ECG.

The aim of this study was to use the vectorial information in the conventional 12-lead electrocardiographic (ECG) recording and to investigate whether this information, in combination with well-known ECG criteria, could increase the diagnostic performance for healed anterior or inferior myocardial infarction. A total of 1,458 subjects were included in the study; 272 patients with anterior myocardial infarction, 356 patients with inferior myocardial infarction, and 830 subjects classified as normal. New 12-lead vectorcardiographic criteria for anterior and inferior myocardial infarction were developed and used in combination with well-known ECG criteria. The combined criteria showed a sensitivity of 80.0% and 72.4% for the diagnosis of anterior and inferior myocardial infarction, respectively. The corresponding sensitivities for the conventional ECG criteria were significantly lower. In conclusion, the addition of vectorial parameters into ECG interpretation programs could be of value.

Diagnosis, Computer-Assisted↗

New carborane-based compounds for boron neutron capture therapy: binding and toxicity of ANC-1, DAC-1 and B-Et-11-OMe in cultured human glioma and mouse melanoma cells.

The toxicity and binding of the three new carborane based compounds: 2 (1,2-dicarba-closo-dodecaborane (12)-1(-yl-methoxy)-2-(3-amino-propyl))-1,3-propanediol, called DAC-1; 7-(3-amino-propyl)-7,8-dicarba-nido-undecarborate (-1) called ANC-1; and rac-1-(9-o-carboranyl)-nonyl-2-methyl-glycero-3- phosphocholine, called B-Et-11-OMe, were analyzed with cultured human glioma cells, U-343MGa, and mouse melanoma cells, B16, as biological models. The previously developed compound di-sodium undecahydro-mercapto-closo-dodecarborate (BSH), which is tested for therapy of malignant gliomas, was analyzed for comparison. In the toxicity tests the cells were exposed to the substances at cell culture medium concentrations in the range 0-50 ppm boron for 1 or 20 h and thereafter analyzed regarding growth. Growth-disturbing effects were seen for the two compounds DAC-1 and B-Et-11-OMe at the concentrations corresponding to 15 and 50 ppm boron, respectively. The compounds ANC-1 and BSH showed no growth-disturbing effects at the tested concentrations. In the binding tests, the cells were incubated for 20 h at about the highest compound concentrations that did not cause growth disturbances. The boron content in the cells was then determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) and in some cases ICP-mass spectrometry (ICP-MS). The most extensive binding was seen for DAC-1 and B-Et-11-OMe, which accumulated boron to about 100 and 60 times, respectively, compared with the concentration in the culture medium. The compound ANC-1 also accumulated boron in the cells but the boron could be easily washed out indicating no or only a weak binding. BSH did not accumulate. Further analysis should be made regarding biological properties such as intracellular compartmentalization, metabolic interference and tumor specificity of the compounds DAC-1 and B-Et-11-OMe.

Animals↗

Determination of selenium in fish flesh by hydride generation atomic absorption spectrometry.

Selenium was determined in freeze-dried fish flesh from perch, pike-perch and the fish flesh reference materials MA-A-2 No. 1174 and MA-B-3 No. 151 (both from the International Atomic Energy Agency) by hydride generation atomic absorption spectrometry. Four different decomposition procedures were tested. They yielded consistent results for the four specimens, but the certified concentration level of selenium in the reference material MA-A-2 was not reached. This indicated losses or the presence of very stable selenium-containing compounds in this fish flesh. Neutron activation analysis of the reference material, however, was in agreement with those results obtained.

Animals↗

Characterization of the antinociception induced by intrathecally administered carbachol.

The antinociceptive effect of intrathecally administered carbachol at the L1/L2 level in the rat was evaluated using the tail immersion test. A dose dependent increase in the nociceptive reaction times was evident following intrathecal carbachol in the dose range of 2.5-15 micrograms. At doses of 20 micrograms and above, although still effective in the test, motor impairment was pronounced. The antinociception was antagonized with atropine, and with either pirenzepine (PZ) or AFDX 116, which are selective M1 and M2 muscarinic receptor blocking drugs, respectively. Spinal cholinergic pain modulation was also studied in rats pretreated with DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), which causes a selective depletion of the noradrenergic nerve fibres in the CNS. The increased latency times after spinal carbachol were attenuated in animals depleted of spinal noradrenaline by DSP4. In conclusion, spinal analgesia by carbachol in the rat may therefore be mediated through both M1 and M2 muscarinic receptor stimulation in the spinal cord. It is also concluded that this spinal cholinergic pain modulation is interacting with spinal noradrenergic nerve terminals, but that the mechanism of the interaction remains to be established.

Analgesics↗

Atomic absorption spectrometric determination of selenium in human blood components.

We separated blood from five healthy blood donors into plasma, erythrocytes, platelets, and leukocytes; counted the number of cells in each fraction; and determined the selenium content of each component by hydride generation atomic absorption spectrometry. The mean (+/- SD) selenium concentrations and amounts measured were as follows: whole blood 102.3 +/- 16.1 micrograms/L, plasma 76.9 +/- 10.6 micrograms/L, erythrocytes 13.7 +/- 2.8 ag per cell, platelets 4.8 +/- 1.1 ag per cell, and leukocytes 99 +/- 26 ag per cell.

Blood Platelets↗

Response of plasma endorphins, prolactin and catecholamines in women to intense heat in a sauna.

Concentrations of immunoreactive beta-endorphin (ir beta-E), corticotropin, cortisol, prolactin and catecholamines in plasma were followed in 11 healthy women during and after exposure to intense heat in a Finnish sauna bath, and compared to those in a similar control situation without exposure to heat. Heat stress significantly increased prolactin and norepinephrine secretion; the percentage increases from the initial plasma concentrations varied from 113 to 1280% (mean 510%) and from 18 to 150% (mean 86%), respectively. The response of the plasma levels of epinephrine, ir beta-E, corticotropin and cortisol to heat exposure was variable. Compared to the control situation, no statistically significant effect of heat exposure on the plasma levels of these hormones was found.

Adrenocorticotropic Hormone↗

Fluorimetry of selenium in body fluids after digestion with nitric acid, magnesium nitrate hexahydrate, and hydrochloric acid.

A digestion procedure involving nitric acid, magnesium nitrate hexahydrate, and hydrochloric acid suffices for selenium determinations in whole blood, serum, and urine by molecular fluorescence spectrometry. To test the accuracy of the method we compared the results with those from hydride-generation atomic absorption spectrometry, and we also analyzed reference materials.

Humans↗

Stress of delivery and plasma endorphins and catecholamines in the newborn infant.

Cord plasma levels of endorphins and catecholamines were correlated with the values of cord blood gas analysis and with hemodynamic parameters in 11 newborns (group A) delivered by elective cesarean section and in 18 newborns (group B) born spontaneously by vaginal route. All infants were in a good condition. No statistically significant differences were found in the mean cord plasma levels of adrenaline (A), noradrenaline (NA) and immunoreactive beta-endorphin (ir beta-E) between groups A and B. After spontaneous labor in group B a highly significant negative correlation was found between plasma NA level and pH and a positive correlation between NA and carbon dioxide tension in cord arterial blood and between NA and the short-term variability of the fetal heart rate before birth. Cord plasma A and ir beta-E did not show such correlations. These findings show that cord plasma level of NA is a sensitive indicator of minor stress during normal labor. After birth, during the first two hours of life, the mean plasma level of ir beta-E decreased in group B after vaginal delivery, but remained at a higher level in group A after elective cesarean section. This shows that the mode of delivery influences the neonatal endorphin secretion.

Blood Gas Analysis↗

Stress hormones and placental steroids in physical exercise during pregnancy.

The hormonal responses to exercise during later pregnancy were studied in relation to an exercise test in ten healthy women. At the end of the 10-min exercise, maternal heart rate had risen from 93 +/- 3.2 (mean +/- SEM) to 157 +/- 6.3 beats/min, and systolic blood pressure from 120 +/- 3.4 to 148 +/- 5.4 mmHg, but diastolic blood pressure was unchanged. Plasma concentrations of noradrenaline and adrenaline rose rapidly during the exercise, from 2.9 +/- 0.3 to 6.9 +/- 1.2 nmol/l and from 0.31 +/- 0.04 to 0.47 +/- 0.08 nmol/l respectively. The serum concentration of prolactin did not change during the test, but 30 min after the exercise the value had risen from 146 +/- 17 to 212 +/- 22 mg/ml, thereafter slowly declining. The serum concentration of cortisol remained unchanged. The mean concentration of oestriol rose from 31.5 +/- 2.6 to 33.9 +/- 3.0 nmol/l at least 5 min after the exercise, thereafter declining to 29 +/- 2.6 nmol/l. After the test, levels of progesterone and oestradiol also fell slightly. Mild irregular uterine activity was found in four subjects. Cardiotocography revealed a transient fetal tachycardia in two subjects.

Adult↗

Stability of human plasma catecholamines.

Human plasma catecholamines, measured by a radioenzymatic method, in general exhibit a marked stability when stored in plasma or whole blood. The storage of blood samples for several hours at room temperature, without prior separation of plasma, did not result in any losses of plasma noradrenaline or adrenaline. Moreover, the addition of thiol compounds (such as reduced glutathione, 2-mercaptoethanol or dithiothreitol) or other antioxidants (sodium metabisulphite) was not required during the storage. Although catecholamines were stable when kept in whole blood at room temperature, they were swiftly degraded when stored in buffer solutions in the absence of thiols. In one subject adrenaline and noradrenaline were repeatedly found to increase significantly in concentration in the course of the first 30 min of storage. The reason for this anomalous increase is unknown. The observed stability of catecholamines in blood is in striking contrast to some earlier reports. It appears to be premature to categorically neglect any precautions as regards the centrifugation, sampling and processing blood samples used for plasma catecholamine determinations; however, when a given routine method is employed one may check the apparent stability of noradrenaline and adrenaline. In some cases this may justify omitting some of the tedious and expensive arrangements suggested in the literature for sample processing.

Adult↗