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Biomedical subjects

B Jensen

Publications and source records attributed to B Jensen.

At least 19 recordsLinked to original sources

Uptake of phenylacetic acid by two strains of Penicillium chrysogenum.

Uptake of phenylacetic acid, the side-chain precursor of benzylpenicillin, was studied in Penicillium chrysogenum Wisconsin 54-1255 and in a strain yielding high levels of penicillin. In penicillin fermentations with the high-yielding strain, 100% recovery of phenylacetic acid in benzylpenicillin was found, whereas in the Wisconsin strain only 17% of the supplied phenylacetic acid was incorporated into benzylpenicillin while the rest was metabolized. Accumulation of total phenylacetic acid-derived carbon in the cells was nonsaturable in both strains at high external concentrations of phenylacetic acid (250-3500 microM), and in the high-yielding strain at low phenylacetic acid concentrations (2. 8-100 microM), indicating that phenylacetic acid enters the cells by simple diffusion, as concluded earlier for P. chrysogenum by other authors. However, at low external concentrations of phenylacetic acid saturable accumulation appeared in the Wisconsin strain. HPLC-analyses of cell extracts from the Wisconsin strain showed that phenylacetic acid was metabolized immediately after entry into the cells and different [14C]-labeled metabolites were detected in the cells. Up to approximately 50% of the accumulated phenylacetic acid was metabolized during the transport-assay period, the conversion having an impact on the uptake experiments. Nevertheless, accumulation of free unchanged phenylacetic acid in the cells showed saturation kinetics, suggesting the possible involvement of a high-affinity carrier in uptake of phenylacetic acid in P. chrysogenum Wisconsin 54-1255. At high concentrations of phenylacetic acid, contribution to uptake by this carrier is minor in comparison to simple diffusion and therefore, of no importance in the industrial production of penicillin.

Bacteriological Techniques

Micellar electrokinetic capillary chromatography for therapeutic drug monitoring of carbamazepine and its main metabolites.

In carbamazepine (CBZ) therapy the concomitant monitoring of concentrations of CBZ and its metabolites is strictly recommended, primarily to avoid toxic side effects. Currently, clinical routine monitoring of CBZ is accomplished by high-performance liquid chromatography or immunological methods. In this study a micellar electrokinetic capillary chromatographic (MECC) method was developed for routine drug monitoring of CBZ and its main metabolites, carbamazepine 10,11-diol and carbamazepine 10,11-epoxide, in human serum or plasma samples. The MECC method enabled baseline separation of all analytes within 2.5 min. The assay revealed sufficient precision and sensitivity and the results of either an automated HPLC or the MECC chromatography assay were in good agreement (r=-0.97). The maximum deviation for CBZ was 0.26 microM.

Anticonvulsants

Effect of N-linked glycosylation on secretion, activity, and stability of alpha-amylase from Aspergillus oryzae.

The effect of N-linked glycosylation on secretion, activity, and stability of alpha-amylase from Aspergillus oryzae grown as dispersed filaments was studied. In the presence of tunicamycin the fungus grew either as dispersed filaments or as one large pellet, whereas growth was as dispersed filaments in all control cultures. The presence of tunicamycin affected neither biomass, level of secreted alpha-amylase, nor total amount of secreted protein in cultures growing as dispersed filaments. In these cultures both glycosylated and nonglycosylated alpha-amylase appeared in the culture medium as well as in the cells, whereas in control cultures only the glycosylated form of alpha-amylase was found in the medium and in the cells. The presence of nonglycosylated alpha-amylase in the medium seemed to result from active secretion rather than from autolysis of the mycelium or extracellular deglycosylation. Deglycosylation with Endo H of crude alpha-amylase in culture filtrate did not affect its stability towards heat, acid pH, or proteolytic degradation.

Aspergillus oryzae

The effects of a physical training program on patients with osteoarthritis of the knees.

OBJECTIVE: To investigate physical function in patients with severe osteoarthritis (OA) of the knees during and after a general physical training program. DESIGN: Randomized control trial, blinded observer, follow-up at 3 months and 1 year. SETTING: Outpatient clinic. PATIENTS: Consecutive sample of 25 patients (3 men, 22 women) with OA of the knees according to the criteria of the American College of Rheumatology (ACR). Two patients (8%) failed to complete the study. There were no withdrawals for adverse effects. INTERVENTION: Twelve patients received training in groups of 6, twice a week for 3 months. Training focused on general fitness, balance, coordination, stretching, and lower extremity muscle strength, and included a daily home exercise program. MAIN OUTCOME MEASURES: Muscle strength across the knee (extension and flexion), Algofunctional Index (AFI), pain (0 to 10 point scale), walking speed, clinical findings. RESULTS: Patients participated in 96 of 96 assessments (100%) and in 218 of 280 training sessions (77.9%). From baseline to 3 months, isokinetic quadriceps strength (30 degrees/sec) improved 20% (confidence interval [CI] 2alpha = .05, 8% to 50%) in the least affected leg; isometric strength improved 21%. By 1 year, AFI had decreased 3.8 points (CI2alpha = .05, 1.0 to 7.0), pain had decreased 2.0 points (CI2alpha = 05, 0.0 to 4.0), and walking speed had increased 13% (CI2alpha = .05, 4% to 23%). There was an increase in the frequency of palpable joint effusions (p < .01) on the most affected side. Frequency of crepitus decreased on the least affected side (p < .01). CONCLUSIONS: General physical training appears to be beneficial to patients with OA of the knee. As shown by the high compliance and low dropout frequency, such a program is feasible even in patients with severe OA of the knee.

Aged

Acceptance of dental care following early extractions under rectal sedation with diazepam in preschool children.

The aim of the study was to evaluate the effect of amnesia in preschool children on their later acceptance of dental care. Forty-six 4-6-year-old children, who between 2 and 4 years previously had had primary incisors extracted because of trauma, were reexamined for dental health and acceptance of dental care. The extractions had been performed under rectal sedation with diazepam (0.7 mg/kg body weight). Information about dental treatment and degree of cooperation during the intervening period was obtained from records at the referring clinic. The parents were interviewed about their child's experience of amnesia concerning the extractions, background variables, and experiences of dental care before the follow-up examination. Amnesia concerning the extractions was reported in 85% of the children. Twenty-nine percent had on some occasion exhibited behavior management problems (BMP) during the intervening period. Lack of amnesia was significantly associated with BMP (P< 0.002). Children without amnesia concerning the extractions tended to accept dental care less well at the reexamination. Parents were able to predict their child's acceptance of dental care at the follow-up with a significant degree of success (P= 0.02). In conclusion, amnesia in preschool children concerning extractions seems to be essential to facilitate positive acceptance of future dental care.

Administration, Rectal

Ultrasound-Doppler technique for monitoring blood flow in the brachial artery compared with occlusion plethysmography of the forearm.

Blood flow changes in the brachial artery of seven subjects during and after submaximal static handgrip contractions were measured by duplex Doppler ultrasound technique. These measurements were compared with the results of occlusion plethysmography, measured immediately (2-3 heartbeats) after. For the combined data from all measurements, a common calibration line could be drawn (linear regression, r=0.92). The flow measurements from the two methods were tested by a four-way analysis of variance and there was no significant difference between the methods during (static) exercise, indicating acceptable coherence. Occlusion plethysmography may well be used for monitoring forearm blood flow during conditions of static exercise. In addition, the cuff occlusion pressure of the plethysmograph (50 mmHg) decreased the blood flow of the brachial artery by approximately 28% as measured by duplex Doppler ultrasound.

Adult

A repetition-prediction study of European parasuicide populations: a summary of the first report from part II of the WHO/EURO Multicentre Study on Parasuicide in co-operation with the EC concerted action on attempted suicide.

One of the aims of the European Study on Parasuicide, which was initiated by the Regional Office for the European Region of the World Health Organization in the mid-1980s, was to try to identify social and personal characteristics that are predictive of future suicidal behaviour. A follow-up interview study (the Repetition-Prediction Study) was designed, and to date 1145 first-wave interviews have been conducted at nine research centres, representing seven European countries. The present paper provides an abridged version of the first report from the study. The design and the instrument used (The European Parasuicide Study Interview Schedules, EPSIS I and II) are described. Some basic characteristics of the samples from the various centres, such as sex, age, method of suicide attempt, and history of previous attempts, are presented and compared. The male/female sex ratio ranged from 0.41 to 0.85; the mean age range for men was 33-45 years and that for women was 29-45 years. At all of the centres, self-poisoning was the most frequently employed method. On average, more than 50% of all respondents had attempted suicide at least once previously. The representativeness of the samples is discussed. There were differences between the centres in several respects, and also in some cases the representativeness of the different samples varied. Results obtained from analyses based on pooled data should therefore be treated with caution.

Adolescent

Proteolytic cleavage of soybean Bowman-Birk inhibitor monitored by means of high-performance capillary electrophoresis. Implications for the mechanism of proteinase inhibitors.

The hydrolysis of the soybean Bowman-Birk inhibitor in the presence of catalytic amounts of bovine trypsin and the formation of the non-covalent enzyme-inhibitor complex with an equimolar amount of enzyme are monitored by means of high-performance capillary electrophoresis (HPCE). The inhibitor is cleaved in the trypsin-reactive and more slowly in the chymotrypsin-reactive subdomain. HPCE proves itself as the only reliable analytical tool to monitor these reactions in clear contrast to classical electrophoretic, chromatographic and enzymatic methods. The most efficient separation of the intact and the two active site cleaved forms of the inhibitor was achieved in borate buffer at pH 10.0. The pH dependence of the rate constant and the final extent of hydrolysis reveal the stability of the enzyme inhibitor complex as a central aspect of the mechanism of proteinase inhibitors.

Amino Acid Sequence

Conformational analysis of acetylcholine and related choline esters.

The crystal structures of carbamoylcholine [2-(carbamoyloxy)-N,N,N-trimethylethanaminium] chloride, bromide and iodide, methoxycarbonylcholine [2-(methoxycarbonyloxy)-N,N,N-trimethylethanaminium] iodide, acetylcholine [2-(acetyloxy)-N,N,N-trimethylethanaminium] chloride and succinylcholine ¿2,2'-[(1,4-dioxo-1,4-butanediyl)bis(oxy)]bis(N,N,N-trimethylet hanaminium)¿ iodide have been redetermined at 105 K in order to obtain detailed and accurate information on the geometry of choline esters and to elucidate the conformationally dependent changes of geometry. The conformational flexibility and the preferred conformations are elucidated based on results obtained from X-ray crystallographic studies and molecular mechanics (MM2) calculations. The usefulness of molecular mechanics calculations for quaternary ammonium ions is discussed.

Acetylcholine

Pharmacokinetics of retinoids in women after meal consumption or vitamin A supplementation.

These studies were conducted to evaluate the pharmacokinetics of several retinoids after meal consumption or vitamin A supplementation to establish a reference for future assessment of teratogenic risks of retinoid therapeutic agents. In the first study, 36 healthy young female volunteers consumed single meals containing vitamin A amounts ranging from 1,305 to 169,474 IU. In the second study, 24 other female volunteers took vitamin A supplements at a dose level of 5,000, 10,000, or 25,000 IU/day for 60 days. Plasma concentrations of tretinoin, isotretinoin, 4-oxo-tretinoin, and 4-oxo-isotretinoin in samples collected during the studies were analyzed using a high-performance liquid chromatography method with ultraviolet detection. Pharmacokinetic parameters for the retinoids were calculated using model-independent methods. Plasma concentrations of tretinoin were not altered by meal consumption or vitamin A supplementation. Plasma levels of 4-oxo-tretinoin were below the assay detection limit (0.3 ng/mL) in the majority of samples collected throughout the studies. Linear relationships between dose and maximum concentration (Cmax) and dose and area under the concentration-time curve (AUC) for isotretinoin and 4-oxo-isotretinoin were derived from data from the meal study. For the most bioavailable formulation used in the supplement study, daily ingestion of 5,000 IU of vitamin A caused increases of 141 +/- 53% and 171 +/- 77% from baseline in the 24-hour AUCs of isotretinoin and 4-oxo-isotretinoin, respectively. Dose-related increases in systemic exposure to retinoids were observed after ingestion of vitamin A by means of a meal or a supplement. Findings from these studies can be used as a basis for future safety evaluations of retinoid compounds.

Adult

Extracellular alpha-Glucosidase with Dextran-Hydrolyzing Activity from the Thermophilic Fungus, Thermomyces lanuginosus

The thermophilic fungus Thermomyces lanuginosus, which is able to use dextran as primary carbon source for growth, excreted during the early phases of growth an enzyme activity capable of degrading dextran. The activity peaked at 22 h and decreased rapidly after the culture entered the stationary phase, probably caused by protease activity. Results from growth on a number of different carbon sources showed that polymer carbohydrates yielded the highest dextranase activities. On the basis of the substrate specificity and the release of glucose in the alpha-anomeric form from the hydrolysis of maltose, it is proposed that the enzyme responsible for the necessary degradation of dextran to smaller saccharides is an alpha-glucosidase.

Journal Article

Alcohol problems among suicide attempters in the Nordic countries.

The purpose of this study was to see whether and how the number of suicide attempters with alcohol problems and their drinking habits differ between the Nordic areas under study. Problem-drinkers were defined as persons who themselves felt that they had an alcohol problem. The analyses were based on data collected at five Nordic research centers participating in the WHO/Euro Multicentre Study on Parasuicide, namely: Helsinki (Finland); Umeå and Stockholm (Sweden); Słr-Trłndelag (Norway); and Odense (Denmark). The results showed that the frequency of problem-drinking among suicide attempters differed markedly between the areas under study; the Finnish male and the Danish female suicide attempters included the highest proportions of self-identified problem-drinkers. The pattern of drinking among the suicide attempters also differed between the areas. The analyses indicate that the point when alcohol becomes a problem to somebody, especially to a degree that it increases the risk of suicidal behavior, not only depends on how much and how often the person drinks alcohol; the prevailing drinking pattern, the attitudes towards drinking alcohol, and the level of social control are also important factors to take into consideration when relations between alcohol and suicidal behavior are under study.

Adolescent

Efficacy of high-intensity exercise training on left ventricular ejection fraction in men with coronary artery disease (the Training Level Comparison Study).

The purpose of this study was to compare high- versus low-intensity exercise training on the change in echocardiographic left ventricular ejection fraction (LVEF) from rest to peak exercise. Sedentary men with coronary artery disease, aged 30 to 70 years, were randomized to dynamic exercise training of either low intensity, 50% of maximal oxygen consumption, n = 89; or high intensity, 85% of maximal oxygen consumption, n = 111. No other interventions were imposed and patients were evaluated at 6 months and 1 year. Both exercise groups significantly increased exercise capacity without adverse events, but the increase was greater (p = 0.02) in the high-intensity exercise group. The mean exercise test rest-peak LVEF in the high-intensity group rose from 6.20% at baseline to 6.54% in 6 months and to 6.73% at 12 months, while the low-intensity group showed no improvement at 6 months and a decrease at 12 months. Multivariate analyses revealed that treatment group (high versus low intensity) significantly contributed to the change in rest-peak LVEF. When the exercise groups were subdivided by initial baseline LVEF < or = 50% versus > 50%, those with the higher LVEF in the high-intensity group showed a greater (p = 0.05) increase in the rest-peak LVEF from baseline to 1 year. Over a 1-year period, exercise capacity improved in both exercise-intensity groups, but more so in the high-intensity group, with no adverse events. The high-intensity group, compared with the low-intensity, showed more improvement in the rest-peak LVEF, especially in those with a higher LVEF at baseline.

Adult