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Biomedical subjects

T Engel

Publications and source records attributed to T Engel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Structure-activity studies of human sterol carrier protein 2.

Recombinant human sterol carrier protein 2 (SCP2) variants were generated by site-directed mutagenesis and expression in Escherichia coli. The ability of the variants to stimulate microsomal conversion of 7-dehydrocholesterol to cholesterol (sterol carrier activity) and to transfer cholesterol and phosphatidylcholine from donor small unilamellar vesicles to acceptor membranes (cholesterol and phosphatidylcholine transfer activities) was compared with wild-type recombinant SCP2. Our results indicate that all measured activities of recombinant human pre-SCP2 (including the 20-amino acid leader sequence) and mature SCP2 were similar. Expressed glutathione S-transferase fusion proteins (GST-SCP2 and GST-pre-SCP2) possessed considerable activity, suggesting that steric obstruction at the amino terminus causes only minor inactivation. The effect of progressive removal of peptides from the carboxyl terminus showed that amino acids between Lys100 and Asn104 are essential for SCP2 activity. This conclusion was substantiated by the observation that replacing Asn104 with Asp or Ile caused considerable inactivation, whereas replacing Met105 with Leu had almost no effect. Since N-ethylmaleimide is known to inhibit SCP2 activity, substitutions were also introduced in the vicinity of Cys71. Whereas Val71 and Ser71 variants possessed wild-type activity, replacing Asp70 with Asn almost completely abolished SCP2 activity. Further, the importance of residues located close to the amino terminus was indicated by complete inactivation of a 10-amino-terminal amino acid deletion mutant and by replacing Leu20 with Glu. Circular dichroism results showed that Leu20 and Asp70 may serve to stabilize the overall fold, whereas residue 104 appears to play a role in the specific lipid binding and/or transfer activity of SCP2.

Amino Acid Sequence↗
PubMed1994

Stable bioenergetic status despite substantial changes in blood flow and tissue oxygenation in a rat tumour.

Experiments on s.c. rat tumours (DS sarcoma) were performed to determine whether chronic or acute changes in tumour perfusion necessarily lead to changes in tissue oxygenation and bioenergetic status since, as a rule, blood flow is thought to be the ultimate determinant of the tumour bioenergetic status. Based on this study, there is clear experimental evidence that growth-related or acute (following i.v. administration of tumour necrosis factor alpha) decreases in tumour blood flow are accompanied by parallel alterations in tissue oxygenation. In contrast, tumour energy status remains stable as long as flow values do not fall below 0.4-0.5 ml g-1 min-1, and provided that glucose as the main substrate can be recruited from the enlarged interstitial compartment. Perfusion rate seems to play a paramount role in determining energy status only in low-flow tumours or low-flow tissue areas.

Adenosine Triphosphate↗
PubMed1992

Acute effects of tumor necrosis factor alpha or lymphotoxin on global blood flow, laser Doppler flux, and bioenergetic status of subcutaneous rodent tumors.

Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon application of the cytokines a significant drop in TBF was found at t greater than or equal to 90 min with a stronger action following rhLT than rhTNF-alpha. At relatively constant mean arterial blood pressure values following the cytokine injection, the microcirculatory function in the tumor periphery was found to be impaired somewhat earlier than TBF, indicating that the cytokines do not preferentially act on the poorly perfused tumor center in the model chosen. This finding is inconsistent with previous histological studies on murine tumors. Acute flow changes encompassed only substantial reductions (i.e., hypoperfusion) rather than a complete ischemia. TBF was slightly increased during the first hour following rhLT whereas after rhTNF-alpha a continuous drop was observed. This differential response could not be observed during laser Doppler flowmetry. Tumor vascular resistance changes largely reflected alterations in TBF. 31P-Nuclear magnetic resonance spectroscopy on murine Meth-A fibrosarcomas revealed dose- and time-dependent decreases of ATP/Pi and phosphocreatine/Pi ratios following i.v. administration of rhTNF-alpha. From comparisons of dose-response curves rhLT appears to be more detrimental than rhTNF-alpha with respect to the bioenergetic status. The observed changes in tumor energy metabolism are similar to those described for TBF. It may therefore be concluded that most of the cytokine effects on the bioenergetic status are secondary to the inhibition of the microcirculatory function. As a major causative factor for the latter, an arterial hypotension can be excluded in the tumor model chosen.

Adenosine Triphosphate↗
PubMed1992

The effect of bipolar electrosurgical coagulation waveform on a rat uterine model of fallopian tube sterilization.

Laparoscopic bipolar electrosurgical sterilization has been employed for nearly two decades. This bipolar procedure was intended to reduce the incidence of unintended complications, such as bowel burns. However, compared to the monopolar procedure, it produced a higher failure rate. This study examines the role of the low power-high voltage coagulation waveform on the effectiveness of electrosurgical desiccation on the rat uterine model of the fallopian tube. Desiccations were performed with both Kleppinger and Storz forceps using generator settings from 2 to 6. Desiccations performed to the visual endpoint (blanch, swell, and collapse) required from 23.8 to 30.0 joules, although procedures performed at a generator setting of 2 required long application times, an average 15.4 sec (Storz) and 28.2 (Kleppinger). All bipolar procedures led to a loss of tissue at the desiccation site at 12 weeks postsurgery. Therefore, the electrosurgical coagulation waveform proved to be effective in producing adequate in vivo tissue destruction even at very low generator settings.

Animals↗
PubMed1992

Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes.

1. The efficacy of a metered dose inhaler (MDI) is highly dependent on the mode of inhalation. The relatively high built-in resistance in the Turbohaler (TBH), a new dry powder inhaler device for inhalation of terbutaline sulphate and budesonide, reduces the flow during inhalation. We compared five different modes of inhalation using the terbutaline TBH in 10 stable asthmatic subjects, who were tested on 5 consecutive days. 2. Measurement of 10 different parameters of pulmonary function indicated that the full bronchodilatory effect of an inhaled dose was already achieved at 5 min after the inhalation. Inspiratory flows through the TBH varying from 34 to 88 l min-1 resulted in comparable bronchodilation, and a previous exhalation to residual volume proved of no value. However, if, prior to inhalation, an exhalation through the device was performed, a substantially reduced effect was seen. 3. Reducing the inspiratory flow to approximately 34 l min-1 produced slightly reduced side effects and lower plasma terbutaline concentrations.

Adult↗
PubMed1992

Airway calibre as a confounder in interpreting bronchial responsiveness in asthma.

BACKGROUND: The relation between airway responsiveness to constrictor agents and forced expiratory volume in one second (FEV1) is important when interpreting change in airway responsiveness after an intervention. The aim of the study was to analyse the relation between FEV1 as a percentage of predicted values (% predicted) and airway responsiveness between and within asthmatic subjects. METHODS: Results of non-specific bronchial challenge tests were pooled from two randomised crossover studies comparing the effect of a non-sedative antihistamine with placebo in 35 patients with moderate asthma. The design of the two studies was similar: the provocative concentration of either histamine (first study) or methacholine (second study) resulting in a 20% decrease in ventilatory capacity (PC20) was repeated at two week intervals while patients were treated with the antihistamine or placebo. The dose of inhaled corticosteroid was gradually reduced during the study. Data were analysed with PC20 as the dependent variable in a general linear model so that the influence on PC20 of inhaled corticosteroid dose, antihistamine, and choice of bronchoconstricting agent could be separated from the influence of FEV1% predicted. RESULTS: The correlation coefficient between mean PC20 and mean prechallenge FEV1 for each patient was 0.45. In the general linear model two thirds (65%) of the variation in PC20 was due to variation between subjects. One third of the within subject variation in PC20 could be explained by variation in prechallenge FEV1% predicted (a change in FEV1 of 27% predicted was associated with one doubling or halving of PC20). Treatment with the antihistamine had no influence on PC20, except when histamine was used as the bronchoconstricting agent. The dose of inhaled corticosteroid had a small but significant effect. CONCLUSIONS: The variation in a patient's PC20 over time (several months) is related to changes in FEV1% predicted. Variation in FEV1% predicted explains less of the variation in bronchial responsiveness between subjects where a patient specific factor, which is probably related to the pathogenesis of bronchial asthma, seems to dominate.

Adrenal Cortex Hormones↗
PubMed1991

The interaction of electrosurgical bipolar forceps and generators on an animal model of fallopian tube sterilization.

Electrosurgical tubal sterilization with bipolar forceps has shown a variable and, in certain studies, a high failure rate. Some physicians have questioned if failure rates are due to an incompatibility between bipolar forceps and bipolar generators of different manufacturers. This manuscript presents data on tissue desiccations performed on a rat uterine horn model that uses two bipolar forceps of quite different designs and two popular bipolar generators. The data demonstrate that if an appropriate amount of energy, between 100 and 117 J, is applied to the tissue, consistent destruction occurs, regardless of the generator-forceps combination used. Histologic examination of the desiccated uterine horns displayed complete occlusion of all samples 8 weeks after the procedure. However, immediately and at 3 weeks after the procedure patent uterine horns were found. In the patent samples most samples displayed considerable electrosurgical damage.

Animals↗
PubMed1991

Single-dose inhaled budesonide in subjects with chronic asthma.

In 30 stable asthmatics, a comparison was made between the changes in pulmonary function (FEV1, FVC, PEF, MEF75, MEF50 and MEF25) hourly for 9 h after a single dose of inhaled budesonide 1,600 micrograms, and placebo. All subjects used inhaled steroids daily; this medication was, however, withheld 8 days prior to the study. For all parameters of pulmonary function, a significant difference in favour of budesonide was demonstrated. The effect tended to decrease after 9 h, and had abated within 24 h. FEV1 age, sex, smoking habits, or results of an inhaled beta 2-agonist reversibility test could not be demonstrated as predictors of those subjects to react with the most pronounced responses to budesonide. In conclusion, our results demonstrate an effect 3 h after administration of an inhaled glucocorticosteroid in adult outpatients with chronic asthma. These results parallel previous findings in highly selected asthmatics and after systemic administration of glucocorticosteroids. Single-dose administration and subsequent monitoring for 8-9 h may therefore prove valuable in evaluating new prophylactic agents for the treatment of asthma.

Administration, Inhalation↗
PubMed1991

Glucocorticosteroid therapy in acute severe asthma--a critical review.

Glucocorticosteroid (GCS) therapy is one of the corner-stones in the treatment of asthma. Its value in acute severe asthma is still open for debate. Many of the papers published on the topic are subject to methodological problems. In 8 of 13 placebo-controlled studies, GCS therapy proved to be superior to placebo, evaluated either as result of pulmonary function, blood gas tension, or hospital admission rate. The most important point for GCS therapy in acute severe asthma seems to be frequent dosage, typically 4 times daily. Oral and intravenous administration seem to have equal efficacy. Only 2 of 10 studies were able to prove a dose-response relationship. Both studies included very low doses of GCS. Doses of 100-200 mg of methylprednisolone for 24 h seem as effective as high doses. A protective effect against relapses within a certain time after the GCS therapy has been demonstrated only for periods not exceeding 4 weeks, and only in children. So far, no study has been able to depict the categories of patients who may or may not benefit by the addition of GCS therapy to the symptomatic treatment of acute severe asthma.

Acute Disease↗
PubMed1990

Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.

Acute Disease↗
PubMed1990

Peak inspiratory flow and inspiratory vital capacity of patients with asthma measured with and without a new dry-powder inhaler device (Turbuhaler).

In 101 asthmatic adults with varying degrees of bronchial obstruction, lung function tests including peak inspiratory flow (PIF), inspiratory vital capacity (IVC), peak expiratory flow (PEF), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) measurements were made. Significant correlations between inspiratory and expiratory volumes were found. In most patients, PIF was less reduced than the expiratory parameters of pulmonary function. When inhalation was performed through the new multi-dose, dry-powder inhalation device, Turbuhaler (PIF-TBH), it was significantly lower than PIF measured without Turbuhaler. In previous studies, PIF-TBH of 30 l.min-1 or more has proven sufficient to produce a therapeutic dose of terbutaline, and to produce significant bronchodilatation. Of 101 asthmatics in the present study, only four had PIF-TBH of less than 30 l.min-1. Although no parameters of spirometry could accurately predict PIF-TBH, there was a tendency for patients with severely impaired ventilatory capacity to produce lower PIF-TBH than patients with normal or near-normal ventilatory capacity. If patients with severely impaired ventilatory capacity are to receive inhalation therapy through Turbuhaler, either PIF or PIF-TBH should be measured, or the effect should be carefully monitored.

Adult↗
PubMed1989

A comparison of two RAST methods and skin prick testing in the diagnosis of wasp venom allergy.

With the aim of evaluating the correlation between skin prick test and two radioallergosorbent tests (RAST) using paper (P-RAST) and Al(OH)3 (Al-RAST) as sorbent materials, 45 consecutive patients known to have been stung by wasp within 6 months were examined. Four patients had a normal reaction, four a large local reaction and 37 a systemic reaction. We found a good correlation between a systemic reaction and a positive P-RAST. Fifty-one per cent of patients with a systemic reaction had a negative Al-RAST, whereas only 8% had a negative P-RAST. Eight per cent of patients with a systemic reaction had a negative SPT. In the eight patients without a systemic reaction, the same patient reacted positively in Al-RAST and P-RAST.

Adolescent↗