Biomedical subjects

R W de Boer

Publications and source records attributed to R W de Boer.

At least 19 recordsLinked to original sources

PubMed1995

Enhanced antitumor effects of CD20 over CD19 monoclonal antibodies in a nude mouse xenograft model.

We used a nude mouse xenograft tumor model to compare the efficacy of unconjugated CD19 and CD20 mAbs (IgG2a subclass) in mediating antilymphoma effects. Treatment with the CD20 mAbs NKI-B20 and BCA-B20 resulted in a drastic decrease in tumor take rate (P < 0.0001) in comparison to controls, whereas the CD19 mAb CLB-CD19 was ineffective. Tumor growth rates were reduced by both CD19 and CD20 (P < 0.0001). The decrease in growth rate induced by NKI-B20 or BCA-B20 was larger than that induced by CLB-CD19 (P = 0.0022). In vitro experiments showed that NKI-B20 or BCA-B20 are more powerful than CLB-CD19 in mediating lysis by interleukin 2-activated natural killer cells. No difference was observed between different isotypes (IgG1, IgG2a, IgG2b) of the switch variants of NKI-B20 or CLB-CD19. A positive correlation between antigen density and the sensitivity to antibody-dependent cellular cytotoxicity was demonstrated with human lymphoblastoid B cells, JY, transfected with cDNA encoding the human CD19 antigen that expressed high levels of this antigen. These cells are more efficiently killed by natural killer cells when coated with CLB-CD19 mAbs than JY wildtype cells that express 1 log lower levels of the CD19 antigen. Antibody-dependent cellular cytotoxicity experiments with thioglycolate-activated macrophages show a more complex relationship between antigen density, isotype of the mAb, and cytotoxicity. BCA-B20 (IgG2a) and CLB-CD19 (IgG2a) and all isotypes of NKI-B20 mediated strong cytotoxicity, whereas CLB-CD19 isotypes IgG1 and IgG2b were associated with limited cytotoxicity. Proliferation of Daudi cells was inhibited with high concentrations of all isotypes of CLB-CD19, but not with any of the CD20 mAbs. To our knowledge this is the first report showing that the antitumor effects in vivo of unconjugated CD20 mAbs are far superior to those of CD19 mAbs.

Animals↗

PubMed1995

Exercise performance as a function of semi-solid and liquid carbohydrate feedings during prolonged exercise.

Aim of this study was to examine the effects of a semi-solid and a liquid carbohydrate feeding on exercise performance. Thirty-two male triathletes performed three exercise trials (3 hours maximal at 75% VO2max) with either a semi-solid feeding (S), an iso-caloric liquid feeding (F) or a liquid placebo (P). Exercise consisted of cycling (bout 1 and 3) and running (bout 2 and 4). Survival analysis revealed that the median maximum test time (MTT) with F, S and P was 180, 126 and 120 min, respectively. Median MTT was longer with F than with S (sign-test; p < 0.05) or P (p < 0.001), with no difference between S and P. Mean power output during supra-maximal tests after bout 2 (W1) and at the end of exercise (Wend) were 371, 365, 362 and 334, 332, 321 W with F, S and P, respectively. Differences between F and P were significant (p < 0.01). Regression analysis identified five variables that were associated with 93% of the variance in MTT. The variance in W1 was explained for 83% by three variables. Wend was explained (90%) by three variables. A significant dietary contribution to MTT and Wend was found, but not to W1. This suggests that the influence of the feedings on performance is different among performance tests.

Adult↗

PubMed1995

Characterization of human gait by means of body center of mass oscillations derived from ground reaction forces.

Ground reaction forces from two force plates are used to determine the cyclic oscillations of the body center of mass while walking at preferred speed. Good approximations to the oscillations may be obtained from formulae containing just the first- and second-order Fourier coefficients of the combined left-right ground reaction forces taken over a complete walking cycle. The symmetric components of the oscillations have consistent mutual phase relations for normal subjects, so that the amplitudes alone can be used as sufficient parameters to characterize the body center of mass oscillations. The analytical technique enables detection of small but consistent gait asymmetries.

Adolescent↗

PubMed1994

Sequence of the HAP3 transcription factor of Kluyveromyces lactis predicts the presence of a novel 4-cysteine zinc-finger motif.

The Kluyveromyces lactis homologue of the Saccharomyces cerevisiae HAP3 gene was isolated by functional complementation of the respiratory-deficient phenotype of the S. cerevisiae hap3::HIS4 strain SHY40. The KlHAP3 gene encodes a protein of 205 amino acids, of which the central B-domain of 90 residues is highly homologous to HAP3 counterparts of S. cerevisiae and higher eukaryotes. The protein contains a novel 4-cysteine zinc-finger motif and we propose by analogy that all other homologous HAP3 proteins contain the same motif, with the position containing the third cysteine being occupied by a serine residue. In contrast to the situation in S. cerevisiae, disruption of the KlHAP3 gene in K. lactis does not result in a respiratory-deficient phenotype and the growth of the null strain is indistinguishable from wild type. There is also no effect on the expression of the carbon source-regulated KlCYC1 gene, suggesting either a different role for the HAP2/3/4 complex, or the existence of a different mechanism of carbon source regulation. Sequence verification of the S. cerevisiae HAP3 locus reveals that, just as in K. lactis, a long open reading frame (ORF) is present upstream of the HAP3 gene. These highly homologous ORFs are predicted to have at least eight membrane-spanning fragments, but do not show significant homology to any known sequence present in databases. The ScORFX gene is transcribed in the opposite direction to ScHAP3, but, in contrast to an earlier report by Hahn et al. (1988), the transcripts of the two genes do not overlap. The model proposed by these authors, in which the ScHAP3 gene is regulated by an anti-sense non-coding mRNA, is therefore not correct.

Amino Acid Sequence↗

PubMed1994

Inflow versus deoxyhemoglobin effects in BOLD functional MRI using gradient echoes at 1.5 T.

Modified gradient-echo MR techniques were applied to study the effects of inflow on functional brain imaging studies using visual and motor cortex stimulation. The results demonstrate that the large signal changes, seen in previously reported gradient-echo studies at 1.5-2.0 T, are dominated by direct inflow effects, in particular when using a large flip angle and a thin slice. The findings suggest that inflow-based functional imaging, along with Blood Oxygenation Level Dependent (BOLD) functional MRI, may play an important role in future research towards the functional organization of the human brain.

Angiography↗

PubMed1994

Changes in phosphorus compounds and water content in skeletal muscle due to eccentric exercise.

The interrelationship of the time courses of soreness and oedema, and of force and phosphorus metabolites after eccentric exercise was studied. Eight male subjects performed 120 maximal eccentric contractions with their left forearm flexors. Soreness, maximal force, flexion and extension elbow angle, and creatine kinase and myoglobin efflux were followed for 96 h after exercise. For equal periods T1 and T2 relaxation times and muscle cross-sectional area were calculated from magnetic resonance images as indications of oedema, and inorganic phosphate (P(i)) and phosphocreatine (PCr) were measured with magnetic resonance spectroscopy. Soreness on extension increased at 1 h (P = 0.043), T1 and T2 (both P = 0.01) and soreness when the arm was pressed (P = 0.028) at 24 h, and muscle cross-sectional area increased at 48 h (P = 0.01) after exercise. Soreness on extension reached a maximum at 48 h, the other four parameters at 72 h. All parameters related to oedema, and soreness, showed an increasing pattern for the period after exercise as a whole, but the largest increase between two points of measurement occurred earlier for soreness than for oedema. Creatine kinase increased significantly from baseline from 24 h onwards (P = 0.017) and myoglobin from 1 h onwards (P = 0.012). The P(i):PCr ratio differed from baseline for the first time 24 h after exercise (P = 0.018), increased to 225%, and then remained on a plateau until 72 h. Maximal isotonic force decreased to 53% at 1 h (P = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Dose-effect relations for local functional and structural changes of the lung after irradiation for malignant lymphoma.

PURPOSE: To estimate the dose-effect relations for local functional (ventilation and perfusion) and structural (density) changes of the lung, 3-4 months after irradiation. METHODS: Twenty-five patients with malignant lymphoma were irradiated with a (modified) mantle field to an average dose of 38 Gy, given in 21 fractions. Single photon emission computed tomography (SPECT) ventilation (V) and perfusion (Q) scans, and CT scans were performed before and 3-4 months after radiation treatment. The three-dimensional dose distribution was calculated using the CT data. After correlation of SPECT and CT data sets, the average post-treatment value of V, Q and lung density per voxel was calculated relative to the pre-treatment value, per dose interval of 4 Gy. Subsequently, the dose-effect relations in each patient were normalized to the average value per voxel in the dose interval of 0-12 Gy. In addition, in each dose interval of 4 Gy the fraction of patients with changes larger than 20% was calculated for all three parameters. The dose-effect relations for perfusion and ventilation normalized to the low-dose regions, and the dose-incidence curves for the fraction of patients with changes larger than 20% were fitted for all three parameters, using a logistic model. RESULTS: Marked changes in the distribution of V and Q were found after irradiation. Prior to normalization to the low-dose regions, a change in V and Q was found in most patients in the dose interval of 0-12 Gy, varying from an increase of 37% to a decrease of 10%, which was followed by a decreasing trend at higher doses. The increase in the low-dose regions indicated a redistribution phenomenon, the magnitude of which was dependent of the irradiated volume. The logistic fit of the dose-effect relations for Q and V, normalized to the low-dose regions, resulted in values for D50 of 51 Gy and 54 Gy (given in 21 fractions on average), respectively, and for the steepness parameter k of 4.2 and 4.0, respectively. The logistic fit for the dose-incidence curves for Q, V and lung density resulted in values for D50 and k of 38 Gy, 37 Gy, 44 Gy and 10.3, 7.8 and 9.4, respectively. CONCLUSIONS: With the combined use of SPECT and CT scans, we have obtained dose-effect relations for local functional and structural damage in the lung, 3-4 months after irradiation.

Adolescent↗

PubMed1994

31P-MRS and simultaneous quantification of dynamic human quadriceps exercise in a whole body MR scanner.

An ergometer for dynamic quadriceps exercise in a magnetic resonance (MR) scanner is physiologically validated, and its technical aspects are presented. The reproducibility of heart rate (HR), O2 consumption (VO2), and power (P) during two graded exercises on the MR ergometer was good (n = 8). Graded exercises on the MR ergometer and on a cycle ergometer (n = 17) were similar with respect to the regression lines between 1) HR and VO2 and 2) HR and P; also peak P did not differ significantly (280 +/- 37 and 298 +/- 41 W, respectively). Peak HR (171 +/- 14 and 184 +/- 15 beats/min, respectively), peak VO2 (3.00 +/- 0.51 and 3.54 +/- 0.44 l/min, respectively), and the slope of the regression line between P and VO2 were lower for MR exercise (P < 0.01). During quadriceps exercise in an MR scanner (n = 12), peak P was 64-143 W for the right leg, with corresponding inorganic phosphate-to-phosphocreatine ratios of 0.85-7.2. It is concluded that continuous noninvasive assessment of energy metabolism with 31P-MR spectroscopy and quantification of power output can be performed simultaneously during dynamic quadriceps exercise, without major reduction of the spectral resolution or the signal-to-noise ratio, and that exercise on this MR ergometer currently is the best possible approximation of cycling exercise for MR purposes.

Adult↗

PubMed1994

Quantifying local lung perfusion and ventilation using correlated SPECT and CT data.

UNLABELLED: A clinically applicable method for quantifying lung perfusion and ventilation on a subregional (local) scale from SPECT scans in order to estimate local lung function in patients with pre-existing pulmonary disease and to monitor local treatment effects was developed and evaluated. METHODS: SPECT 99mTc perfusion and 81mKr ventilation images were corrected for photon attenuation and scatter effect with a postreconstruction correction method incorporating a variable-effective linear-attenuation coefficient calculated from spatially-correlated CT data. A new algorithm was developed to quantify local ventilation from the SPECT data, which, in contrast with other algorithms, makes no assumptions on ventilation homogeneity over the lung. The quantification procedure was applied to clinical data from patients with a normal lung function and from patients suffering from radiation-induced pulmonary dysfunction. RESULTS: The calculated attenuation correction factors on the observed number of counts in the lung range from 2.0 to 3.0 and 2.3 to 3.5 for 81mKr and 99mTc, respectively, showing a systematic increase from the diaphragm to the lung apex. As a result of this correction, the values of local perfusion and ventilation differ 10%-15% from values calculated without attenuation correction. The calculated values of the local ventilation are 10%-50% lower than those found by quantification algorithms which assume homogeneous ventilation. CONCLUSIONS: The methods presented here are robust with respect to uncertainties in the input parameters and yield realistic values for perfusion and ventilation distribution in the lung with an intrinsic accuracy (largely determined by count statistics) of about 10%.

Algorithms↗

PubMed1993

A new method to determine dose-effect relations for local lung-function changes using correlated SPECT and CT data.

PURPOSE: To determine dose-effect relations for regional lung-function changes after radiotherapy. METHODS: Single Photon Emission Computed Tomography (SPECT) was performed to quantify regional ventilation and perfusion. CT scans were used to calculate the three-dimensional (3-D) dose distribution. Both SPECT and CT scans were performed prior to radiotherapy and 5 months after the start of the treatment. To obtain combined 3-D information on ventilation, perfusion and dose, the SPECT data were correlated with the corresponding CT data. The relative changes in ventilation and perfusion were calculated in each SPECT voxel (voxel size about 6 x 6 x 6 mm) and related to the dose in that voxel. The average relative changes were determined per dose interval of 4 Gy. This procedure was evaluated using the data from five patients treated for Hodgkin's disease with mantle field irradiation with a prescribed total dose of 40-42 Gy. RESULTS: Dose-effect relations for perfusion were observed in all patients, while in four of the five patients, a dose-effect relation was found for ventilation. The maximal uncertainty of the calculated radiation dose was 11%: a difference between the position of the patient during treatment and during CT scanning caused a maximal dose uncertainty of 6%, while the accuracy of the dose calculation algorithm itself was estimated to be within 5%. CONCLUSION: The results indicate that the combined use of SPECT and CT information is an effective method for determining dose-effect relations for regional lung function parameters in each individual patient.

Adolescent↗

PubMed1993

Gastrointestinal problems as a function of carbohydrate supplements and mode of exercise.

The aim of the study was to examine prevalence and duration/seriousness of gastrointestinal (GI) problems as a function of carbohydrate-rich (CHO) supplements and mode of exercise. The relationship between GI problems and a variety of physiological and personal factors (age, exercise experience) was also examined. Thirty-two male tri-athletes performed three experimental trials at 1-wk intervals, each trial on a different supplement: a conventional, semisolid supplement (S; 1.2 g CHO, 0.1 g protein, and 0.02 g fat.kg BW-1 x h-1); an almost isocaloric fluid supplement (F; 1.3 g CHO.kg BW-1 x h-1, no fat, no protein); and a fluid placebo (P). The 3 h of exercise started at 75% VO2max and consisted of alternately cycling (bouts 1 and 3) and running (bouts 2 and 4). GI symptoms were monitored by a questionnaire. Analysis of variance revealed that nausea lasted longer with P as compared with S (P < 0.05). Bloating lasted longer during bout 3 with P as compared with F and S (P < 0.05). Accounting for confounding factors, most GI symptoms occurred more frequently and lasted longer during running than during cycling. Multiple regression analysis revealed significant relationships between nausea and urge to defecate, between an urge to defecate, GI cramps and flatulence, and between belching and side ache. From all other factors energy depletion, CHO malabsorption, exercise intensity, exercise experience, and age were significantly related to GI symptoms during the exercise.

Adult↗

PubMed1992

Body fat distribution in pubertal girls quantified by magnetic resonance imaging.

We examined body fat distribution in relation to anthropometrically derived variables in 24 girls in early and late stages of puberty. The amounts of subcutaneous and intra-abdominal body fat were derived from transverse slices at the levels of the waist, hip and trochanter using magnetic resonance imaging (MRI), and were compared to the related circumferences, the circumference ratios and the trunk-to-extremity skinfold ratios. Waist, hip and trochanter circumferences were highly correlated to the respective related MRI total fat surface area both in early and late pubertal girls (r = 0.79-0.97), while waist circumference, and waist-hip, waist-thigh or skinfold ratios were not significantly correlated to intra-abdominal fat areas. Late pubertal girls (n = 11) were significantly taller, heavier and fatter compared to early pubertal girls (n = 13), yet their anthropometric waist-to-hip or waist-to-trochanter circumference ratios were significantly lower. The intra-abdominal fat area measured in a transverse MRI section at the level of the waist was 24.1 +/- 4.1 cm2 in early pubertal girls and 25.7 +/- 4.1 cm2 in late pubertal girls (mean +/- s.e.m.). As compared to early pubertal girls, the MRI derived amount of subcutaneous fat in late pubertal girls was significantly higher at the trochanter level (142.1 +/- 12.7 vs. 201.3 +/- 26.3 cm2; P less than 0.05). We conclude that circumferences at the trunk are good measures for the related amounts of fat in pubertal girls. In contrast conventional anthropometric measurements, such as trunk-to-extremity skinfold ratio or waist-to-hip circumference ratio, cannot be used to predict the amount of intra-abdominal fat in pubertal girls.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1990

Dose-volume correlation in radiation-related late small-bowel complications: a clinical study.

The effects of the volume of irradiated small bowel on late small-bowel tolerance was studied, taking into account the equivalent total dose and type of pre-irradiation surgical procedure. A method was developed to estimate small-bowel volumes in the high-dose region of the radiation treatment using CT-scans in the treatment position. Using this method small-bowel volumes were measured for three-field and AP-PA pelvic treatments (165 cm3 and 400 cm3, respectively), extended AP-PA pelvic treatment (790 cm3), AP-PA treatment of para-aortic nodes (550 cm3) and AP-PA treatment of para-aortic and iliac nodes (1000 cm3). In a retrospective study of 111 patients irradiated after surgery for rectal or recto-sigmoid cancer to a dose of 45-50 Gy in 5 weeks, extended AP-PA pelvic treatment (n = 27) resulted in a high incidence of severe small-bowel complications (37%), whereas for limited (three-field) pelvic treatment (n = 84) the complication rate was 6%. These complication data together with data from the literature on postoperative radiation-related small-bowel complications were analysed using the maximum likelihood method to fit the data to the logistic form of the dose-response relation, taking the volume effect into account by a power law. The analysis indicated that the incidence of radiation-related small-bowel complications was higher after rectal surgery than after other types of surgery, which might be explained by the development of more adhesions. For both types of surgery a volume exponent of the power-law of 0.26 +/- 0.05 was established. This means that if the small-bowel volume is increased by a factor of 2, the total dose has to be reduced by 17% for the same incidence of small-bowel complications.

Carcinoma↗

PubMed1988

Supramaximal test results of male and female speed skaters with particular reference to methodological problems.

Six male and six female elite speed skaters were tested during two bicycle ergometer tests: a 30 s sprint test and a 2.5 min supra maximal test. During the 2.5 min test oxygen consumption was measured every 30 s. The males showed 30-31% higher mean power output values both during the sprint test (1103 versus 769 Watt) and during the 2.5 min test (570 versus 390 Watt). Maximal oxygen consumption was 31% higher for the males than for the females (5.10 versus 3.50 1.min-1). However, when expressed per kilogram lean body weight (LBM), power output and oxygen consumption was equal for both sexes. Differences between present and previous results are most likely due to methodological problems with the estimation of load during the supra maximal test. Subjects appear to experience difficulties in distributing their power output over the 2.5 min if they are tested for the first time. For experienced skaters and cyclists, fixed levels of 19 W.kgLBM-1 as initial load setting for the sprint test and 8 W.kg LBM-1 for the 2.5 min test are recommended.

Adipose Tissue↗

PubMed1988

A geometrical model of speed skating the curves.

The centripetal force in speed skating the curves has to be delivered by the push off force which also does the external work to maintain the speed. Based on the geometry of the speed skating oval and the sideward push off characteristics in speed skating, a mathematical model of the power output in skating the curves was deduced. The power required to follow the curve is dependent on the mean speed in the curve, the work per stroke and the radius of the speed skating oval. Measurements (by means of film and video analysis) during the 5000 m races at the European Championships for ladies (n = 16) yielded on the one hand power from the geometrical model and on the other hand power losses due to air- and ice- friction. The difference between power delivered and power lost is used by the skaters to increase their speed. The difference between predicted power and measured power used to increase the kinetic energy of c.g. was only 3% thereby providing strong support for the validity of the model. The analysis suggested that skaters who want to accelerate in the curves should increase their work per stroke. The model can be a useful tool to provide insight into this form of human locomotion and its optimization under competitive conditions.

Acceleration↗

PubMed1988

The use of the D versus dD plot to estimate the alpha/beta ratio from iso-effect radiation damage data.

In studies of radiation damage, the parameter alpha/beta of the linear-quadratic (LQ) model is usually estimated from iso-effect data by plotting the iso-effect doses in a so-called Fe-plot, which is a plot of the inverse total dose versus dose per fraction. This method, however, is statistically not well founded. A better, but relatively complex technique to estimate the alpha/beta ratio was described by Tucker. The present contribution shows that results, virtually identical to the ones of Tucker can be obtained in a very simple way if the iso-effect doses are plotted as total dose Dn versus the product of dose per fraction and total dose, Dndn. A reliable estimator of the alpha/beta ratio consists then of the negative inverse slope of the linear-regression line in this plot. The presentation of iso-effect data in such a D-dD plot highlights deviations from the LQ model more clearly than does the Fe-plot. It is therefore suggested to use the D-dD plot as a quick and easy graphical scheme to obtain an estimate of alpha/beta.

Animals↗

PubMed1987

Physiological and biomechanical comparison of roller skating and speed skating on ice.

Eight well trained marathon skaters performed all-out exercise tests during speed skating on ice and roller skating. To compare these skating activities in relation to the concept of training specificity, relevant physiological (VO2, VE, RER and heart rate) and biomechanical variables (derived from film and video analysis) were measured. There were no significant differences between oxygen uptake (50.5 +/- 8.0 and 53.3 +/- 6.7 ml.min-1.kg-1), ventilation (102.4 +/- 11.2 and 116.0 +/- 11.1 1.min-1) or heart rate (174 +/- 12.2 and 176 +/- 14.5 min-1) between speed and roller skating. In roller skating a higher RER (1.16 +/- 0.1 cf. 1.05 +/- 0.1) was found. Power, work per stroke and stroke frequency were equal. Due to a higher coefficient of friction the maximal roller skating speed was lower. The effectiveness of push-off and parameters concerning the skating techniques showed no differences. In roller skating a 7.5% higher angle of the upper leg in the gliding phase occurred. It is speculated that the blood flow through the extensor muscles might be higher in roller skating. It is concluded that roller skating can be considered as a specific training method which may be used by trained speed skaters in the summer period.

Adult↗

PubMed1987

Moments of force, power, and muscle coordination in speed-skating.

Two well-trained speed-skaters were subjected to a biomechanical analysis incorporating push-off forces, cinematographic data, and link segment modeling. To gain knowledge on the backgrounds on technique and performance in speed-skating, the muscle coordination was studied by EMG and muscle contraction velocities. In speed-skating during the push-off, the body center of gravity (cg) is accelerated with respect to the point of application of the push-off force, with a forward gliding skate. The velocity of cg is a result of rotation of segments. Due to the absence of plantar flexion of the foot, the knee extension range is limited. The short and explosive push-off can be considered as a catapult-like action. The knee extensor muscles vastus medialis and rectus femoris are prestretched in the gliding phase by the antagonistic action of gastrocnemius and biceps femoris. In this phase the skater rotates his cg from the lateral to the medial side of the skate to reach an optimal push-off angle. The power output in the push-off phase is mainly generated by the monoarticular extensor muscles gluteus maximus and vastus medialis.

Ankle Joint↗