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Biomedical subjects

H Pedersen

Publications and source records attributed to H Pedersen.

At least 37 records · Page 2Linked to original sources
PubMed1991

A novel function of the cAMP-CRP complex in Escherichia coli: cAMP-CRP functions as an adaptor for the CytR repressor in the deo operon.

Unlike classical bacterial repressors, the CytR repressor of Escherichia coli cannot independently regulate gene expression. Here we show that CytR binding to the deoP2 promoter relies on interaction with the master gene regulatory protein, CRP, and, furthermore, that cAMP-CRP and CytR bind co-operatively to deoP2. Using mutant promoters we show that tandem, properly spaced DNA-bound cAMP-CRP complexes are required for this co-operative binding. These data suggest that CytR forms a bridge between tandem cAMP-CRP complexes, and that cAMP-CRP functions as an adaptor for CytR. The implications of this new version of negative control in E. coli on bacterial gene expression and on combinatorial gene regulation in higher organisms are discussed.

Bacterial Proteins↗
PubMed1991

The cyclic AMP (cAMP)-cAMP receptor protein complex functions both as an activator and as a corepressor at the tsx-p2 promoter of Escherichia coli K-12.

The tsx-p2 promoter is one of at least seven Escherichia coli promoters that are activated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex and negatively regulated by the CytR repressor. DNase I footprinting assays were used to study the interactions of these regulatory proteins with the tsx-p2 promoter region and to characterize tsx-p2 regulatory mutants exhibiting an altered response to CytR. We show that the cAMP-CRP activator complex recognizes two sites in tsx-p2 that are separated by 33 bp: a high-affinity site (CRP-1) overlaps the -35 region, and a low-affinity site (CRP-2) is centered around position -74 bp. The CytR repressor protects a DNA segment that is located between the two CRP sites and partially overlaps the CRP-1 target. In combination, the cAMP-CRP and CytR proteins bind cooperatively to tsx-p2, and the nucleoprotein complex formed covers a region of 78 bp extending from the CRP-2 site close to the -10 region. The inducer for the CytR repressor, cytidine, does not prevent in vitro DNA binding of CytR, but releases the repressor from the nucleoprotein complex and leaves the cAMP-CRP activator bound to its two DNA targets. Thus, cytidine interferes with the cooperative DNA binding of cAMP-CRP and CytR to tsx-p2. We characterized four tsx-p2 mutants exhibiting a reduced response to CytR; three carried mutations in the CRP-2 site, and one carried a mutation in the region between CRP-1 and the -10 sequence. Formation of the cAMP-CRP-CytR DNA nucleoprotein complex in vitro was perturbed in each mutant. These data indicate that the CytR repressor relies on the presence of the cAMP-CRP activator complex to regulate tsx-p2 promoter activity and that the formation of an active repression complex requires the combined interactions of cAMP-CRP and CytR at tsx-p2.

Amino Acid Sequence↗
PubMed1990

[Cerebral computed tomography in infantile spasms].

A prospective investigation of 52 children with infantile spasms was carried out employing computed tomography. Normal conditions were demonstrated in 21 (40%). Among the 31 children with pathological computed tomografic findings, dilatation of the ventricular system and/or subarachnoid space was found in nine cases (17%), congenital malformations in ten (19%) and cerebrovascular changes in a similar number (19%). One patient had a tumour and one had congenital toxoplasmosis. No significant differences were found in the frequencies of normal psychomotor development between children with normal and abnormal computed tomographic findings. The reason for this is probably that a good prognosis may be anticipated in the idiopathic forms provided that ACTH treatment is initiated early in the course of the disease. Computed tomography is useful to differentiate between symptomatic and idiopathic cases of infantile spasms. It may, however, be assumed that neuronal heterotopy without other malformations in the central nervous system may be difficult to diagnose with computed tomography. Magnetic resonance scanning will probably be able to demonstrate these cases.

Adrenocorticotropic Hormone↗
PubMed1990

Two stage cultures for the production of berberine in cell suspension cultures of Thalictrum rugosum.

Two stage culture systems were examined in cell suspensions of Thalictrum rugosum which produce berberine in a growth associated manner. The utilization of indole 3-acetic acid (IAA) as a growth regulator, in place of 2,4-dichlorophenoxyacetic acid (2,4-D), at various growth phases was investigated. Although the enhancing effect was clear when it was used separately, in combination with 2,4-D effect of IAA was suppressed and medium change from 2,4-D to IAA was detrimental to product formation. The decrease of berberine production in this two stage culture may be due to the loss of conditioning factors associated with medium replacement.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1990

Thrombolytic therapy of cerebral arterial occlusion with recombinant tissue plasminogen activator.

This report describes three patients, with acute cerebral arterial occlusion, treated with recombinant tissue plasminogen activator (rt-PA). In one patient with basilar artery occlusion thrombolytic treatment was initiated 12 h after onset of the symptoms. In two patients with angiographically verified occlusion of the middle cerebral artery, the treatment was initiated approximately 4.5 h after onset of the symptoms. Recombinant tissue plasminogen activator 80-120 mg, was infused intra-arterially over 90-100 min via a catheter the tip of which was close to the occlusion. This regimen resulted in recanalization in all the patients; however, in two patients it was verified by repeat CT scan only. In two patients the thrombolytic treatment was successful (the patients improved clinically); the third patient died of massive cerebral infarct-related oedema. In none of the patients did significant bleeding or other obvious side-effects occur. From this preliminary report it is concluded that angiographically proven thrombolytic recanalization in acute cerebrovascular occlusion is possible with rt-PA. In some patients, however, the treatment is initiated too late. Further investigation of the possible indication for thrombolytic therapy in stroke is needed.

Adult↗
PubMed1990

Cranial computed tomography in infantile spasms. Primary findings related to long-term mental prognosis.

Out of 109 children with infantile spasms (IS), prospectively tested during the years 1976 to 1979 in Denmark, 52 children were examined by cranial computed tomography (CT). The classification of IS into cryptogenic (CR), symptomatic (SY) and doubtful (DO) was done clinically without considering the CT-findings. Sixty per cent of the scannings were abnormal. Only 6/30 (20%) of the children in ACTH treatment were found to develop cerebral atrophy which means that this finding is not an obligatory side-effect of ACTH treatment of children with IS. Normal CT-findings were found in 50% of the CR and 50% of the SY + DO-groups, and could not be used as a prognostic tool for estimating the mental development. This was also the case for children with cerebral atrophy. Abnormal CT-findings (minus atrophy) were highly correlated to the group with clinical symptoms and indicate an extremely unsatisfying long-term mental prognosis. CT-scanning is a valuable tool for the examination of clearing children with infantile spasms.

Adrenocorticotropic Hormone↗
PubMed1990

Pharmacokinetics of ropivacaine in nonpregnant and pregnant ewes.

The pharmacokinetics of ropivacaine were studied in chronically instrumented nonpregnant and pregnant ewes. On the day of study, the urinary bladder was catheterized. Ropivacaine (2.5 or 3.0 mg/kg) was administered by intravenous infusion over 2 or 4 min. Serial samples of arterial blood and urine were collected over 5 h, and drug concentrations were determined using a gas chromatographic technique. Total clearance of ropivacaine was lower in the pregnant animals (21.6 +/- 4.5 mL.min-1.kg-1) compared with the nonpregnant animals (45.1 +/- 6.7 mL.min-1.kg-1). There was a tendency toward a decrease in the volume of distribution during the terminal exponential phase of drug elimination of 2.03 +/- 0.36 L/kg in the pregnant and 4.32 +/- 1.03 L/kg in the nonpregnant sheep. Thus the difference in the elimination half-life was only minimal: 74.7 +/- 10.7 min in the pregnant and 64.4 +/- 7.4 min in the nonpregnant animals. It is concluded that ovine pregnancy is accompanied by changes in the pharmacokinetics of ropivacaine. Inadvertent intravenous injections of similar drug doses to pregnant and nonpregnant women might result in higher plasma concentrations of ropivacaine in the former. However, the rate of decline in plasma levels of the drug would be similar in both.

Amides↗
PubMed1989

Tallysomycin S10b--a phase I trial.

Tallysomycin S10b is a new bleomycin analogue. In animal studies it has shown the same degree of antineoplastic activity as bleomycin; however in contrast to that of bleomycin, its dose-limiting effect in animal systems is renal toxicity and its pulmonary toxicity is less pronounced. A total of 16 patients received tallysomycin S10b at three exploratory levels: 3 patients were given a dose of 1.25 mg/m2, 9 received 2.5 mg/m2 and 4 were given 5 mg/m2 as i.v. bolus injections twice weekly. Before treatment and every 3 weeks, plain chest X-rays, pulmonary function tests, renography and 51Cr-EDTA clearance were carried out. No renal toxicity was found in any of the treatment groups. In the first two groups no changes in chest X-rays were observed during treatment, whereas in the third group a decrease in single-breath carbon monoxide diffusion capacity (DLCO) was seen in one patient until the treatment was discontinued. Two of four patients receiving 5 mg/m2 developed interstitial pneumonitis at total doses of 104 and 160 mg, respectively. During the trial no haematologic or hepatic changes occurred due to the drug. The frequency of occurrence of skin changes, stomatitis and fever increased with the cumulative dose of tallysomycin S10b, and these side effects were similar to those seen with bleomycin. No tumor regression was seen during the trial. In contrast to the findings in previous animal studies, we found that the dose-limiting effect was pulmonary and not renal toxicity. The recommended dose for further phase II trials is 2.5 mg/m2 twice weekly, with careful monitoring of the pulmonary function.

Adult↗
PubMed1989

Computed tomography in intracranial, supratentorial metastases in children.

This study compares the CT characteristics in a consecutive sample of supratentorial metastases (n = 31) with primary tumors of the same location (n = 49) in childhood. Postcontrast CT was performed in all but one of the metastases cases. In all but one of these children the location and type of primary tumor was known at time of occurrence of cerebral metastasis. Primary CNS tumors (n = 12) had a higher incidense of supratentorial metastatic spread than tumor originating elsewhere. Three children had diffuse subarachnoid seeding, while 28 had solid tumors (21 solitary, 7 multiple). The predilection location for the solid metastases was the gray-white matter junction (n = 12). The following CT findings were significantly less frequent in metastases than in primary tumors (P less than 0.05): Midline location, calcification and cyst formation. On the other hand bleeding, pronounced contrast enhancement and location in the gray-white matter junction were more frequent in the metastatic group (P less than 0.05).

Brain Neoplasms↗
PubMed1989

Malignancy criteria in computed tomography of primary supratentorial tumors in infancy and childhood.

The CT findings of 11 malignant primary supratentorial tumors in children are compared with those of 38 benign tumors. The malignant tumors were more often laterally placed and surrounded by edema. Irregular tumor shape and high or "mixed" density were more frequent in the malignant group where larger tumor volume was found. The contrast enhancement pattern was also different. Thus, ring enhancement with central lucency was more often seen in the malignant tumors. Seven of the malignant tumors had both irregular shape and edema, while this combination was not present in any of the 38 benign tumors.

Astrocytoma↗
PubMed1989

Evaluation of blood-warming devices with the apparent thermal clearance.

Hypothermia (less than 35 C) associated with massive transfusions is a serious clinical problem. Maintenance of normal temperatures in this setting is essential and requires the use of rapid and efficient blood-warming devices. The optimal design of such units should include a low priming volume, large heat transfer area, low pressure drop, the ability to operate at high flow rates, and the capability of warming blood from 4 to 32 C, or higher, without untoward effects. We have previously formulated a theoretic model for blood warmers and described a measure of the intrinsic efficiency of these devices, the apparent thermal clearance (VT,cl). In this study, we tested four different types of commercially available blood warmers (the single-coil immersion heater; the single-channel dry wall electric heater; the multichannel countercurrent heat exchanger; and the single-channel, countercurrent heat exchanger) and determined the apparent thermal clearance values using saline and packed red blood cells. The results indicate that only the single-channel countercurrent unit is efficient enough to meet the established requirements. The apparent thermal clearance provides a useful and rigorous means for comparing and evaluating blood-warming devices.

Blood Transfusion↗
PubMed1989

Does pregnancy alter the systemic toxicity of local anesthetics?

The toxicity of mepivacaine in chronically instrumented nonpregnant and pregnant sheep was evaluated, and compared with data from previous studies of the toxicity of other local anesthetics. Thirteen preparations were studied, seven nonpregnant (NP) and six pregnant (P). Mepivacaine 2 mg.kg-1.min-1 was infused at a constant rate into the femoral vein until toxic manifestations occurred, in the following sequence: convulsions, hypotension, respiratory arrest, and circulatory collapse. The doses and plasma concentrations of mepivacaine necessary to produce toxic symptoms were similar in NP and P animals, whereas, in a previous study, pregnancy enhanced the cardiotoxicity of bupivacaine. No malignant ventricular arrhythmias were observed throughout the study. Protein binding of mepivacaine was also determined in sera from nonpregnant and pregnant ewes and compared with that for bupivacaine. Serum protein binding of mepivacaine was not reduced in pregnancy at the drug concentrations associated with toxic symptoms; at circulatory collapse, it was approximately 22% in NP and P. In contrast, the proportion of bound bupivacaine was 73% in NP and 51% in P, a significant difference. These protein binding data suggest that, although lethal concentrations of bupivacaine, determined in the previous study, were higher in NP than in P animals, concentrations of free drug were similar. Thus, the difference between the two drugs may be related to gestational increases in the availability of free drug in the case of bupivacaine.

Anesthesia, Local↗
PubMed1989

Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb.

Lidocaine was infused at a constant rate of 0.1 mg.kg-1.min-1 for 180 min into 12 chronically prepared pregnant sheep while asphyxia, induced by partial umbilical cord occlusion, was maintained in the premature fetus (80% of gestation). In five similar preparations saline instead of lidocaine was infused into the mother for 180 min. Maternal and fetal arterial blood pressure, heart rate, pHa, PaCO2, and PaO2 were monitored, and fetal cardiac output and the distribution of blood flow to fetal organs were measured, using labeled microspheres, before and after asphyxia and again after maternal infusion of lidocaine or saline. Maternal and fetal arterial blood and maternal urine were obtained at intervals for determination of lidocaine concentrations and urinary drug clearance. At the end of infusion, these animals were killed and tissues dissected for determination of lidocaine concentrations and organ blood flow. Maternal and fetal lidocaine plasma concentrations at steady state were 2.32 +/- 0.12 and 1.23 +/- 0.17 microgram/ml, respectively, similar to those seen during human epidural anesthesia. Asphyxia resulted in a significant drop in fetal heart rate and increased blood flow to the brain, heart, and adrenals. Asphyxia and saline did not produce additional deterioration of the fetus, but asphyxia and lidocaine led to a significant increase in PaCO2 and decreases in pHa, mean arterial pressure, and blood flows to the brain, heart, and adrenals. It is concluded that the immature fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine obtained transplacentally from the mother.

Animals↗
PubMed1989

Angiotensin-converting enzyme inhibition and regional cerebral blood flow in acute stroke.

The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on regional cerebral blood flow (rCBF) was studied in 12 patients within 5 days after their first acute stroke. rCBF was studied by xenon-133 inhalation and single-photon emission computed tomography (SPECT) scan before and 1 h after oral administration of 25 mg captopril. No increase in rCBF was observed in any of the 12 patients included in the study. In only one patient was there a slight redistribution of blood flow in favor of the low-flow area, but the absolute flow value did not increase. Captopril did not cause any significant change in mean hemispheric blood flow, mean arterial blood pressure (MAP), or end-expiratory CO2 fraction (FECO2). The assumption that ACE inhibition might increase cerebral blood flow in the periinfarct zone and preserve some still viable brain tissue could not be verified in the present study.

Acute Disease↗
PubMed1989

Parkinson's disease and autoimmunity.

Sera from 22 patients with Parkinson's disease were tested for autoantibodies in 11 different assays, including a test for autoantibodies directed against determinants in the pituitary gland. All patients were tested twice with a 12-month interval between tests. No pituitary autoantibodies were detected. The other autoantibodies investigated were found in low frequencies and in low titers. Our data supports the view that the pathogenesis of Parkinson's disease is not autoimmune.

Adult↗