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Biomedical subjects

D Andersson

Publications and source records attributed to D Andersson.

At least 37 records · Page 2Linked to original sources

Kinetics of cobalamin repression of the cob operon in Salmonella typhimurium.

The cob operon in Salmonella typhimurium encodes 25 proteins involved in the biosynthesis of cobalamin. Expression of the cob operon is negatively feedback regulated by cobalamin via a translational control mechanism. The concentration of cobalamin required to repress cob expression to half-maximal was determined in vivo and in vitro to 0.4 microM and 0.6 microM, respectively. These results suggest that cob expression in wild-type cells is partially repressed by de novo synthesized cobalamin.

Cloning, Molecular↗

A novel inositol phosphate selectively inhibits vasoconstriction evoked by the sympathetic co-transmitters neuropeptide Y (NPY) and adenosine triphosphate (ATP).

Postganglionic sympathetic nerves release norepinephrine (NE) as their primary neurotransmitter at vascular and other targets. However, much evidence supports involvement of additional messengers, co-transmitters, which are co-released with NE upon sympathetic nerve stimulation and thereby contribute to their actions, e.g., vasoconstriction. Two such putative co-transmitters, neuropeptide Y (NPY) and adenosine triphosphate (ATP) have been of particular interest since they fulfill several neurotransmitter criteria. Importantly, hitherto it has been difficult to antagonize vasoconstriction evoked by either NPY or ATP with agents that are devoid of intrinsic activity. The present study describes the ability of a novel inositol phosphate, D-myo-inositol 1,2,6-trisphosphate (Ins[1,2,6]P3; PP-56) to in vitro potently block vasoconstrictor responses elicited by NPY and ATP, but not by NE, as studied in guinea-pig isolated basilar artery. The action of Ins[1,2,6]P3 does not seem to occur through antagonism at NPY- or ATP-receptor recognition sites, labeled by 125I-peptide YY and 35S-gamma-ATP, respectively, in membranes of rat cultured vena cava vascular smooth muscle cells. However, it does involve inhibition of the influx of Ca2+ induced by either co-transmitter in these same vena cava cells. It is proposed that Ins[1,2,6]P3 may be a useful functional antagonist of non-adrenergic component(s) of the vasoconstrictor response to sympathetic nerve stimulation.

Adenosine Triphosphate↗

Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits.

The vascular smooth muscle contractile response to neuropeptide Y (NPY), potassium, noradrenaline, histamine and serotonin was studied in circular segments of isolated vessels in vitro from rabbits with alloxan-induced diabetes mellitus. The injection of alloxan resulted in a marked and maintained increase in serum glucose as early as 1 week after treatment. Four vessel types were examined: abdominal aorta, and renal, left anterior descending coronary and middle cerebral arteries. There was no difference in the contractile response to histamine or serotonin between control and diabetic vessels. However, in the cerebral artery the contractile response to noradrenaline was reduced in the diabetic group, while in the aorta and the renal artery no significant differences were seen. Noradrenaline failed to evoke any contractile response in the coronary arteries in either group. NPY induced strong, concentration-dependent contractions of coronary and cerebral arteries, but did not have any contractile effect per se in aorta or renal arteries, either in control or in alloxan-treated rabbits. The maximal contractile effect and the sensitivity to NPY was significantly less in diabetic coronary and cerebral vessels as compared to control. There was no difference in dilator effect of acetylcholine and substance P between the diabetic animals and the control group in any of the vessel types, indicating that the changed vascular responses to NPY and noradrenaline were not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of NPY and noradrenaline in the peripheral sympathetic nervous system are selectively attenuated in this model of chronic diabetes.

Animals↗

Papaverine effects on PGI2 and TXA2 release from the canine vascular wall.

Operative manipulation of blood vessels might lead to spasm, thereby destroying the endothelial cell function: the spasm can be prevented by the vasodilator papaverine. To study if this was mediated via the prostanoid pathway the following investigation was undertaken: canine jugular veins and carotid arteries were dissected with or without papaverine. Vessel segments were then perfused with Hank's balanced salt solution for five times 15 min. Prostacyclin was measured as the stable degradation product 6-keto-PGF1 alpha and thromboxane as TXB2, by radioimmunoassay. Control arterial segments' 6-keto-PGF1 alpha release was initially 129.5 + 20.1 pg/mm2/15 min, and 29.7 + 10.4 after 60 min (p less than 0.05 vs initial value) and responded to arachidonic acid (AA) with an increase to 139.2 +/- 23.1 pg/mm2/15 min (p less than 0.05). Segments treated with papaverine had the same release as the controls. In venous segments there was a lower initial release (p less than 0.05) from segments given papaverine than from controls, but this was more likely an effect of papaverine on the assay. There was no difference in release of prostacyclin from segments given papaverine in the perfusate compared to controls when using 125I tracer. When using 3H tracer including absorption of free antigen to dextran coated charcoal, papaverine displaced the free tracer giving artificially low values. There was no effect of papaverine given intraoperatively on the TXB2 release, neither from arteries nor from veins. In another experiment the vessel wall tension was examined and the cyclooxygenase inhibitor diclofenac did not inhibit the vasodilating effect of papaverine.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Gamma 2-MSH increases during graded exercise in healthy subjects: comparison with plasma catecholamines, neuropeptides, aldosterone and renin activity.

To evaluate the possibility that the proopiomelanocortin (POMC)-derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has a role in circulatory regulation in man we studied circulating levels of this peptide at three different stages of physical activity in 10 young healthy subjects. The results were compared to simultaneously measured plasma levels of catecholamines, neuropeptide Y, vasopressin, renin activity, aldosterone and human alpha-atrial natriuretic peptide (alpha-hANP) and of the vasodilatory peptides calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. The plasma levels of gamma 2-MSH-LI (like immunoreactivity) increased from 1009 +/- 101 pmol l-1 at supine rest to 1281 +/- 79 pmol l-1 when measured after 10 min walking (P less than 0.05), and remained at this increased level also after a consecutive further increase of physical activity (4 min stair rush), 1293 +/- 87 pmol l-1 (P less than 0.05 vs. at rest). The increase in circulating gamma 2-MSH-LI levels preceded the elevation of the venous plasma noradrenaline level, but did not rise further with more pronounced activation of the sympathetic nervous system at the highest grade of physical activity examined.

Aldosterone↗

Shoulder function after prosthetic replacement of proximal humerus.

Between 1973 and 1985 eighteen patients with bone tumours and two patients with comminuted fractures had their proximal humerus replaced with a custom made isoelastic hemiendoprosthesis. In 1987 a clinical and radiographical review was performed of eleven patients with a mean follow up time of seven years, range 3-10 years. Four patients had pain at rest and six patients experienced severe pain on exertion. Active range of motion was poor and constituted only half of the corresponding range of passive motion. Shoulder girdle muscles were generally weak, only one patient could keep the arm straight in a flexed or abducted position. All patients had returned to their previous occupations, but their ability to perform ADL functions was poor. Rotator cuff insufficiency was considered to be the major cause of poor shoulder function. In comparison to most other surgical alternatives in tumour cases endoprosthetic replacement of the proximal humerus appears to be a safe and reliable method. The endoprosthesis gives stability to the arm and normal elbow and hand function is preserved.

Adult↗

The epidemiology of sudden infant death syndrome and attacks of lifelessness in Sweden.

Infants who died showing the syndrome of sudden infant death (SIDS) and infants who survived attacks of lifelessness (AL) were examined in a prospective epidemiological multicentre study over 24 months covering close to 40% of all births in Sweden. Seventy SIDS cases and 34 cases of AL were observed, giving an incidence for SIDS of 0.94/1000 and for AL of 0.46/1000. This SIDS incidence is higher than that observed during the seventies. The boy/girl ratio was 1.4:1 for SIDS and 1.6:1 for AL. The age distribution for AL resembled that for SIDS. Similarities were also seen with regard to place of occurrence. Sixty per cent of the SIDS cases occurred during the daytime/evening. Twenty-nine per cent of the infants with AL had more than one apneic spell during the three-day-period around the attack, indicating a period of respiratory instability, but only 12% had such spells later on. None of the infants who had had AL died from SIDS. The possible relationship between AL and SIDS is discussed.

Age Factors↗

The effect of carbon dioxide inhalation on phase characteristics of breathing movements in healthy newborn infants.

Chest wall distortion (inward motion of the rib cage on inspiration) has been found recently to reduce the tidal volume during active sleep in the neonatal period. To determine some of the factors that relate to the chest wall distortion and the decreased tidal volume seen in active sleep, a quantification of the phase differences between the movements of the chest wall and those of the abdominal wall, and of the relation of their phase differences to tidal volume was performed on data obtained before and during carbon dioxide stimulation in 15 newborn infants sleeping in the prone position. In quiet sleep, the breathing movements were congruent and regular, and the tidal volume and the mean inspiratory flow increased during carbon dioxide stimulation. In active sleep during exposure to carbon dioxide, the chest wall distortion decreased, the breathing movements were incongruent and the degree of the chest wall distortion was negatively correlated with the tidal volume, while the tidal volume and the mean inspiratory flow was increased. Chest wall distortion did not appear in quiet sleep and was decreased in active sleep in spite of increased ventilation during CO2 stimulation. This study favours the idea that chest wall distortion is caused by a well regulated change in neuromuscular activity and not by the strength of diaphragmatic movements overcoming the mechanical stability of the rib cage.

Abdomen↗

Effect of Roux-en-Y gastroenterostomy on gastric emptying of a solid meal following antrectomy and vagotomy.

Gastric emptying of a 51Cr labelled solid meal was studied before and at least 6 months after operation for pyloric-prepyloric ulcer disease. All patients underwent an antrectomy, selective gastric vagotomy but 10 were randomized to a gastroduodenostomy and 12 to a Roux-en-Y gastrojejunostomy. There was no significant difference in the emptying rate between patients studied preoperatively (T 75 = 48 +/- 21.8 min) and those investigated after a Billroth I gastroduodenostomy (T 75 = 45 +/- 15.8 min). However, the emptying rate was significantly retarded in the Roux-en-Y patients as compared to those studied preoperatively (T 75 + T 50 + T 25). In the former group, an initial retardation of emptying of the meal was most apparent (T 75 = 89 +/- 81.7 min). Due to a high standard deviation, the difference between the Roux-en-Y and gastroduodenostomy groups did not reach statistical significance. Our results would indicate that retarded gastric emptying is not a regular phenomenon after a Roux-en-Y gastrojejunostomy provided that a selective gastric vagotomy had been performed and the investigation been carried out at least 6 months after the operation.

Adult↗

Hyper-accurate ribosomes inhibit growth.

We have compared both in vivo and in vitro translation by ribosomes from wild-type bacteria with those from streptomycin-resistant (SmR), streptomycin-dependent (SmD) and streptomycin-pseudo-dependent (SmP) mutants. The three mutant bacteria translate more accurately and more slowly in the absence of streptomycin (Sm) than do wild-type bacteria. In particular, the SmP bacteria grow at roughly half the rate of the wild-type in the absence of Sm. The antibiotic stimulates both the growth rate and the translation rate of SmP bacteria by approximately 2-fold, but it simultaneously increases the nonsense suppression rate quite dramatically. Kinetic experiments in vitro show that the greater accuracy and slower translation rates of mutant ribosomes compared with wild-type ribosomes are associated with much more rigorous proofreading activities of SmR, SmD and SmP ribosomes. Sm reduces the proofreading flows of the mutant ribosomes and stimulates their elongation rates. The data suggest that these excessively accurate ribosomes are kinetically less efficient than wild-type ribosomes, and that this inhibits mutant growth rates. The stimulation of the growth of the mutants by Sm results from the enhanced translational efficiency due to the loss of proofreading, which more than offsets the loss of accuracy caused by the antibiotic.

Drug Resistance, Microbial↗

Effect of different starchy foods in composite meals on gastric emptying rate and glucose metabolism. I. Comparisons between potatoes, rice and white beans.

Thirteen healthy subjects participated in the study. Three meals of equal energy content consisting of hamburgers and mashed potatoes, polished rice or white beans were studied. The various meals were labelled with 2.6 MBq 51Cr and gastric emptying was studied by a movable NaI (T1) detector. Blood glucose and plasma insulin were measured after an overnight fast and after ingestion of the testmeal. Gastric emptying of mashed potatoes was faster than that of polished rice (P less than 0.02) and of white beans (P less than 0.05). Blood glucose and plasma insulin responses to the meal with mashed potatoes were greater than to that with polished rice (P less than 0.01), which also produced a greater glucose response than that with white beans (P less than 0.01). The correlation coefficient (rs) between difference in gastric emptying and difference in blood glucose or plasma insulin response was 0.95 (P less than 0.01) when comparing meals of mashed potatoes and polished rice. No correlation was found between gastric emptying and blood glucose or plasma insulin after the white bean meal. We conclude that glucose and insulin responses to potatoes and rice are strongly related to gastric emptying rate, but other factors dominate the control of these responses to white beans.

Adult↗

Simultaneous transcutaneous carbon dioxide and transcutaneous oxygen monitoring in neonatal intensive care.

Continuous transcutaneous carbon dioxide partial pressure (tc PCO2) and continuous transcutaneous oxygen partial pressure (tc PO2) was monitored simultaneously in 10 consecutive neonatal intensive care patients treated for respiratory problems or immaturity. During measurement the electrode temperature was 44 degrees C while during the resting periods--with the electrodes left in situ--the electrode temperature was 37 degrees C. Measurements were performed for periods up to 31 hours. It was possible to discover changes in central blood gas partial pressures also at the lower electrode temperature. This was especially true for the tc PCO2 recording which was less influenced by the decrease in electrode temperature than the tc PO2 recording. In six patients an increased frequency of apnoea was diagnosed by the transcutaneous blood gas monitoring equipment previous to other clinical signs. A statistically highly significant correlation was found between transcutaneous and arterial blood gas values, the arterial samples obtained from umbilical artery catheters. tc PCO2 and tc PO2 very sensitively reacts to changes in the breathing pattern and to changes in activity of the neonate emphasizing the drawbacks of previous blood gas monitoring techniques. The technique for continuous transcutaneous carbon dioxide monitoring is ready for clinical use and is a valuable additional tool in all neonatal intensive care patients with the risk of alveolar hypoventilation.

Carbon Dioxide↗

Phase characteristics of breathing movements in healthy newborns.

In the neonatal period, respiratory distortion of the chest wall in active sleep has been reported to reduce the thoracic gas volume. In order to investigate whether the distortion influences the tidal volume, a thorough quantification of the phase differences between the movements of the chest wall and the abdominal wall and the relation of the phase differences to the ventilation was performed on fifteen newborn infants sleeping in prone position. The changes in the circumference of the chest and abdomen were measured with mercury-in-silastic strain gauges; nasal air flow was monitored with a pneumotachograph. During quiet sleep, the movements of the chest wall and the abdominal wall were congruent and regular, and the tidal volume was not dependent on the observed phase differences between them. In active sleep, the breathing movements were incongruent, the tidal volume was negatively correlated with the phase shift between the movements of the chest wall and the abdominal wall, and the mean inspiratory flow was increased. Ventilation (ml/min) did not differ between the sleep states. This study thus suggests that, in healthy newborns in active sleep, the chest wall distortion leads to a reduction of the tidal volume, but ventilation is upheld by compensatory mechanisms, i.e. increased breathing rate and increased amplitude of movements of the diaphragm.

Abdominal Muscles↗