Search PubMed⌕ Search

Biomedical subjects

W Becker

Publications and source records attributed to W Becker.

At least 55 records · Page 3Linked to original sources

Cloning and characterization of DYRK1B, a novel member of the DYRK family of protein kinases.

The DYRK1A gene on human chromosome 21 encodes a protein kinase presumed to be involved in the pathogenesis of mental retardation in Down's syndrome. Here we describe a highly similar homolog, DYRK1B, which is, in contrast to DYRK1A, predominately expressed in muscle and testis. The human DYRK1B gene was mapped to chromosome 19 (19q12-13.11) by radiation hybrid analysis. The amino acid sequences of DYRK1A and DYRK1B are 84% identical in the N-terminus and the catalytic domain but show no extended sequence similarity in the C-terminal region. DYRK1B contains all motifs characteristic for the DYRK family of protein kinases. In addition, the sequence comprises a bipartite nuclear localization motif. A green fluorescent protein (GFP) fusion protein of DYRK1B was found mainly in the nucleus of transfected COS-7 cells. These data suggest that DYRK1B is a muscle- and testis-specific isoform of DYRK1A and is involved in the regulation of nuclear functions.

Amino Acid Sequence↗

Estimation of self-turning in the dark: comparison between active and passive rotation.

The present work compares passive and active rotations in darkness with the aim of characterizing the contribution of efferent and proprioceptive information to the perception of angular displacement. The perception of angular displacements was measured in 12 naive subjects (Ss), who either stood on a rotating platform (passive mode, P) or actively turned about their vertical axis by stepping around "on the spot" on a stationary platform (active mode, A). Rotations consisted of short acceleration epochs followed by constant velocity periods of 18.5, 37, and 55 degrees /s, with angular displacements ranging from 30 degrees to 810 degrees (presented in a randomized order); in the case of active turning, Ss had learned to approximately produce any of these three velocity levels on command. Ss indicated perceived displacement either verbally (verbal estimation mode, E), or by stopping their rotation when self-displacement appeared to match the magnitude specified by the experimenter (targeting, T). The resulting four conditions (PE, PT, AE, AT) were administered blockwise. In none of the four conditions was there a systematic dependence of perception on turning velocity. Therefore, the results were pooled across velocities, and the Ss' performance was summarized in the form of estimation curves showing median estimates as a function of physical displacement. There were several differences between the passive and active modes: AE- and AT-estimation curves were linear, close to veracity, and fairly similar to each other. In contrast, the PE-curve was curved rightwardly ("saturation"), with small displacements being overestimated and large ones underestimated, whereas the PT-curve was linear and indicated a pronounced overestimation of large displacements. Moreover, both the random and the systematic errors (measures of individual consistency and correctness of individual calibration, respectively) were significantly smaller in the active than in the passive modes. The observed independence of Ss' perception from turning velocity also during passive rotation suggests that the perceptual time constant was significantly longer than 16 s (a value cited as typical for vestibular perception), being possibly "enhanced" by contextual implications and by expectations of the Ss. The clear improvement of perceptual performance in the active mode testifies to the importance of the efferent and proprioceptive signals arising during active motion. On the assumption that these signals are about as "noisy" as the vestibular ones, the smaller errors during active turning could result from their combination with the vestibular signal. Alternatively, they could also be intrinsically less noisy than the vestibular signal and simply replace the latter during active motion. In the context of these alternatives (which are not exhaustive), the general problem of sensory fusion is discussed, that is, by which mechanisms are signals from different sensory sources combined to obtain a unified representation of the self's orientation.

Adult↗

Podokinetic after-rotation does not depend on sensory conflict.

Humans who have been stepping for 10 min or more about their vertical axis on a counterrotating platform while fixating on a stationary visual scene continue to circle in the same direction when they attempt, thereafter, to step on firm ground in darkness without turning ("podokinetic after-rotation": PKAR). In the present report, we investigate whether PKAR is due to: (1) a sensory reinterpretation triggered by the conflict between the visual signal of stationarity and the somatosensory message of feet-on-platform rotation, or (2) an adaptation of the somatosensory afferents to prolonged unilateral stimulation irrespective of visual stimulation. Subjects (Ss) circled for 10 min about their vertical axis on an either stationary or counterrotating platform while they were either in darkness, or exposed to an optokinetic stimulus, or to a "head-fixed" stationary pattern. Thereafter, Ss first stood motionless in darkness for 30 s, allowing vestibular after-effects to decay, and then tried (still without vision) to step in place on the stationary platform without turning while their body rotation was recorded by a potentiometer coupled to the head. All conditions involving podomotor activity without concomitant optokinetic stimulation evoked similar PKAR. With optokinetic stimulation, PKAR became larger, apparently because it was summed with an optokinetically induced after-rotation (oPKAR). This oPKAR could be demonstrated in isolation when Ss were passively rotated in front of the OKN-pattern instead of actively circling. PKAR could not be "dumped"; it reappeared after 30 s of straight stepping under visual control. We suggest that PKAR is caused by adaptation of the somatosensory channel and not by a sensory conflict.

Afferent Pathways↗

Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity.

Dyrk-related kinases represent a novel subfamily of protein kinases with unique structural and enzymatic features. Its members have been identified in distantly related organisms. The yeast kinase, Yak1, has been characterized as a negative regulator of growth. Mnb from Drosophila is encoded by the minibrain gene, whose mutation results in specific defects in neurogenesis. Its mammalian homolog, Dyrk1A, is activated by tyrosine phosphorylation in the activation loop between subdomains VII and VIII of the catalytic domain. The human gene for Dyrk1A is located in the "Down syndrome critical region" of chromosome 21 and is therefore a candidate gene for mental retardation in Down syndrome. More recently, six additional mammalian Dyrk-related kinases have been identified (Dyrk1B, Dyrk1C, Dyrk2, Dyrk3, Dyrk4A, and Dyrk4B). All members of the Dyrk family contain in the activation loop the tyrosines that are essential for the full activity of Dyrk1A. Outside their catalytic domains, Dyrk kinases exhibit little sequence similarity except for a small segment immediately preceding the catalytic domain (DH-box, Dyrk homology box). An unusual enzymatic property of Dyrk-related kinases is their ability to catalyze tyrosine-directed autophosphorylation as well as phosphorylation of serine/threonine residues in exogenous substrates. The exact cellular function of the Dyrk kinases is yet unknown. However, it appears reasonable to assume that they are involved in the regulation of cellular growth and/or development.

Amino Acid Sequence↗

Anterior cruciate ligament and intercondylar notch in the coronal oblique plane: anatomy complemented by magnetic resonance imaging in cruciate ligament-intact knees.

We assessed the anatomy of the anterior cruciate ligament (ACL) and femoral intercondylar notch on cryosections from one cadaveric knee specimen in the coronal oblique plane oriented parallel to the intercondylar roof. We determined the course of the ACL, the widths of the cruciate ligaments at intersection, and the intercondylar notch configuration on coronal oblique plane magnetic resonance images in 51 adult cruciate ligament-intact knees (25 women, 26 men; age range, 16 to 47 years). The intercondylar notch widths were measured at the notch entrance, at the intersection of the ACL and posterior cruciate ligament (PCL), and at the notch outlet. In the coronal oblique plane, the ACL exhibited a diagonal course from the central and medial part of the anterior intercondylar area of the tibia distally, across the lateral third of the intercondylar notch, to the intercondylar surface of the lateral femoral condyle proximally. At the cruciate ligament intersection, the absolute widths of the ACLs measured on average 6.1+/-1.1 mm in men and 5.2+/-1.0 mm in women representing 31.9% and 31.1% of the ACL/central intercondylar notch width ratios. The absolute widths of the PCLs measured on average 9.6+/-1.3 mm in men and 8.5+/-1.3 mm in women representing 50.4% and 51.4% of PCL/central intercondylar notch width ratios. On average for both groups, men and women, the absolute widths of the PCLs were significantly larger than the absolute widths of the ACLs. However, the relative widths of the cruciate ligaments with respect to corresponding intercondylar notch widths were not significantly different. In the coronal oblique plane, the intercondylar notch widths showed on average a significant decrease from posterior to intersection and from intersection to anterior. At notch outlet, the mean notch width measured 21.4 mm in men and 18.5 mm in women. At intersection, the mean notch width measured 19.1 mm in men and 16.6 mm in women. At notch entrance, the notch width measured 14.6+/-1.8 mm in men and 12.7+/-2.1 mm in women. We recommend magnetic resonance tomography of the knee in the coronal oblique plane oriented parallel to the intercondylar roof as the imaging modality of choice to visualize accurately the anatomic diagonal course of the ACL and its relation to the intercondylar notch and posterior cruciate ligament complex.

Adolescent↗

Dietary guidelines and patterns of food and nutrient intake in Sweden.

The Nordic and Swedish Nutrition Recommendations emphasize the balance between macronutrients in the diet. The amount of saturated and total fat should be limited to c. 10 %energy and 30 %energy, respectively, and the amount of total carbohydrates should be 55-60 %energy. Data from the first Swedish national dietary survey in 1989 show that the average diet is too high in fat, especially saturated fat (36-37 %energy and 16 %energy, respectively) while the content of total carbohydrates and dietary fibre is too low. However, parts of the population consume a diet that meets the recommendation for a particular macronutrient. A comparison of subjects with a low or high intake of total fat and saturated fat, dietary fibre or fruit and vegetables show some common trends with respect to the characteristics of a dietary pattern equal or close to the recommendations, e.g. more frequent consumption of fruit and vegetables and a lower consumption of some fat-rich foods, such as spreads, cheese and sausages.

Adolescent↗

Energy under-reporting in Swedish and Irish dietary surveys: implications for food-based dietary guidelines.

An analysis of dietary survey data from Sweden and Ireland revealed that with a declining ratio of energy intake to estimated basal metabolic rate (EI:BMR), %energy from fat, saturated fat and carbohydrate fell while that of protein increased. However, where the definition of under-reporting is less strict, as in the Irish database (EI:BMR) < 1.27), the quantitative effect on macronutrient balance, while statistically significant, is not of such magnitude as to be of nutritional significance. However, with respect to foods, under-reporting was found to be of considerable significance in using such data to formulate food-based dietary guidelines. The Swedish data show that under-reporting of foods is associated with a decreasing percentage of consumers, decreasing intake per eating occasion and decreasing frequency of eating. The development of food-based dietary guidelines will involve comparisons of patterns of food intake among people with contrasting high or low intakes of target nutrients. The Swedish data compared food intakes for those with low or high intakes of saturated fatty acids (SFA) among under-reporters and acceptable reporters of energy intake. Whereas absolute values were always lower with the lower EI:BMR group (< 1.1) compared to the higher EI:BMR group (> 1.35) the ratio of intakes for the low vs. high SFA groups were broadly significant at either EI:BMR ratio. This paper highlights the difficulties that under-reporting will pose for food-based dietary guidelines.

Adolescent↗

Intake of fatty acids in western Europe with emphasis on trans fatty acids: the TRANSFAIR Study.

OBJECTIVE: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. DESIGN AND SUBJECTS: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set. RESULTS: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2-6.7 g/d and 1.7-4.1 g/d, respectively). The TFA intake was lowest in Mediterranean countries (0.5-0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C18:1 were the most TFA in the diet. Monounsaturated fatty acids contributed 9-12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3-7%. CONCLUSION: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included.

Adult↗

Monitoring allergen immunotherapy of pollen-allergic patients: the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome.

BACKGROUND: Although allergen immunotherapy has been established as a treatment of type I allergy back in 1911, until now the underlying mechanisms have not been fully understood, nor are there any parameters which would allow one to monitor an ongoing treatment or to assess therapeutic success in the meantime. OBJECTIVE: We wanted to define allergen-specific parameters that change due to treatment in correlation with the clinical outcome. METHODS: We conducted a controlled study with grass pollen-allergic children and compared allergen-specific antibody titres before and 1 year after the onset of immunotherapy in contrast with untreated allergic and healthy children. Two recombinant forms of the major allergen group V of Phleum pratense (Phl p 5) served as model allergens. RESULTS: No change in IgE levels and no significant reduction of skin prick test (SPT) reactivity were seen. On the other hand, a significant reduction of symptom scores in the treated group and a significant rise in allergen-specific IgG1, IgG2 and IgG4 due to the treatment could be observed, but in neither case could we establish a correlation between the increasing amounts of the single antibody classes and the reduction of symptom scores. But most interestingly, when comparing the ratio of IgG4 to IgG1 with the symptom scores, we found significant correlations. Nevertheless, treated allergic patients still differ considerably from healthy controls as nonatopics have hardly any measurable allergen-specific IgG antibodies and no IgE antibodies at all. CONCLUSION: The ratio of IgG4 to IgG1 can serve as a valuable parameter that allows us to assess the success of immunotherapy already 1 year after the onset. The increase of specific IgG1 in relation to IgG4 during treatment reflects a possible influence of this subclass on the induction of tolerance towards allergens.

Allergens↗

Evaluation of procollagen III peptide as a marker of tissue hyperthyroidism in long-term treated women with TSH suppressive doses of thyroxine.

Increased serum concentrations of the aminoterminal propeptide of collagen III (PIIINP) are found in overt hyperthyroidism. Thus, measurement of serum PIIINP might be useful as an early marker of tissue hyperthyroidism in patients with TSH suppressive thyroxine treatment. In a prospective study we evaluated female patients followed in the thyroid outpatient clinic. Serum PIIINP concentrations were analysed in three groups: patients with TSH suppressive thyroxine treatment for more than 6 months (n = 33, TSH < 0.1 mU/l), patients with thyroxine substitution for hypothyroidism for more than 6 months (n = 20, TSH 0.2-4.0 mU/l) and spontaneous hyperthyroid patients (n = 8, TSH < 0.03 mU/l, increased freeT4 and/or T3). Beside TSH, thyroid hormones and serum PIIINP we measured serum SHBG and a clinical score. Hyperthyroid patients had clearly elevated serum PIIINP and SHBG values and a higher clinical score when compared with other study groups (p < 0.001). Patients with TSH suppressive thyroxine treatment had higher fT4 and T3 concentrations than the thyroxine substitution group (fT4 22 +/- 4.8 pmol/l vs. 17 +/- 2.6 pmol/l, T3 2.2 +/- 0.4 nmol/l vs. 1.8 +/- 0.3 nmol/l, p < 0.001) and also elevated serum SHBG values (77.6 +/- 27.5 nmol/l vs. 58.4 +/- 18 nmol/l, p < 0.01). However, serum PIIINP concentrations and the clinical score were very similar in both thyroxine treated groups (PIIINP in TSH suppression group 3.0 +/- 0.67 microg/l vs. 2.8 +/- 0.65 microg/l in the substitution group, clinical score 2 +/- 1.8 pts. vs. 1.7 +/- 1.5 pts. p = n.s.). In conclusion, serum PIIINP is not a reliable early marker for detection of tissue hyperthyroidism in long-term thyroxine treated women with suppressed TSH.

Adult↗

In vivo stability and metabolism of 99Tcm-labelled anti-CD4 monoclonal antibodies and Fab' fragments.

In a comparative study, the in vivo metabolic profile of 99Tcm-anti-CD4 monoclonal antibodies (MAb) and Fab' fragments (direct thiol-reduction method) was investigated in rats with adjuvant arthritis. Plasma samples were obtained 1, 4 and 15 h following intravenous injection and urine was collected over 15 h. The composition of the radiolabelled molecules was analysed by gel filtration chromatography. The profile of the complete MAb was as follows. (1) Serum: a predominant peak of 150 kDa (complete MAb; approximately 80%); three minor peaks of 125, 100 and 50 kDa (presumably H2L1, H2 and H1 chains; 14%); and two small peaks of approximately 1500 and 300 Da (presumably 99Tcm-glutathione and Cys-99Tcm-Cys; 5%). (2) Urine: minor peaks of 125, 100 and 50 kDa (15%), major peaks of 1500 and 300 Da (50%), and an additional 25-kDa peak (30%). The profile of the Fab' was as follows. (1) Serum: three minor peaks of 150 kDa [conceivably F(ab')2 plus soluble-CD4], 110 kDa [F(ab')2] and 95 kDa (Fab' plus soluble-CD4; together 30%); a predominant peak of 55 kDa (Fab'; 61%); and two minor peaks of 1500 and 300 Da (8%). (2) Urine: predominantly a 55 kDa (16%) and 1500 and 300 Da peaks (74%). Also, the anti-CD4 Fab' showed higher urine excretion and lower plasma levels than the complete anti-CD4 MAb, but still more favourable tissue-to-blood ratios following scintigraphy of the arthritic joints. Thus, the complex metabolic profile of the anti-CD4 Fab' does not appear to interfere with specific targeting of the inflamed synovial membrane.

Animals↗

Immunoreactive leptin and leptin mRNA expression are increased in rat hypo- but not hyperthyroidism.

In this study, plasma leptin concentrations were measured in rats artificially rendered hyper- or hypothyroid by administration of thyroxine or TRH, by administration of methimazole, or by thyroidectomy. Compared with those in untreated controls, leptin immunoreactivity was not affected in the hyperthyroid state, but was significantly increased in hypothyroid animals. Methimazole administration for longer time periods caused a stepwise increase in plasma leptin immunoreactivity. Greatest leptin concentrations were seen after 28 days of methimazole. Seven days after withdrawal of the methimazole, leptin concentrations no longer differed from those observed in control animals. In hypothyroid animals, expression of leptin mRNA was increased in both retroperitoneal and epididymal adipose tissue, whereas no difference was seen for subcutaneous or mesenteric fat. Incubation of rat leptin with plasma of eu- or hypothyroid rats and subsequent HPLC analysis of leptin plasma peaks gave no indication of an altered hormone stability. We conclude that, in hypothyroid rats, leptin concentrations may be increased as a result of stimulated leptin synthesis in retroperitoneal and epididymal adipose tissue.

Adipose Tissue↗

Long-term evaluation of 282 implants in maxillary and mandibular molar positions: a prospective study.

BACKGROUND: Placement of implants into molar positions presents diagnostic, surgical and prosthetic challenges. There are few reported studies for implants placed into molar positions. The purpose of this prospective longitudinal study is to report long-term clinical outcomes for 282 implants placed into molar positions. METHODS: Two-hundred-twelve patients received 282 implants. Implant size, location, jaw shape, and bone quality were recorded for all implants placed into molar positions. Seventy implants were inserted in maxillae and 212 in mandibles. Marginal bone level changes in maxillae and mandibles were measured from non-standardized periapical radiographs taken at abutment connection and an average follow-up of 3.9 years. Mesial-distal implant measurements were made from the top of the implant cylinder to the first point of bone to implant contact. In mandibles, 39 implants were used for single molar replacements, 67 implants were placed into excellent bone quality (type I) and 113 were in good bone quality (type 11); 145 implants were placed into bone with moderate bone resorption (type B); 166 implants were placed in first molar positions and 46 in second molar sites. RESULTS: At 6 years the cumulative success rate (CSR) for mandibular implants is 91.5%, and the success rate from the 2 to 3 year follow-up is 100%. Of the 70 implants placed in maxillae, 16 replaced single molars. Thirty-two implants were placed in jaw shape B with type 2-bone quality. For maxillary implants, the 6-year CSR was 82.9% and the success rate remained steady at 100% after the 2 to 3 year follow-up. For maxillary implants, at abutment connection the average marginal bone level was 1.67 mm, while at follow-up it was 1.98 mm. These differences were statistically significant (P = 0.04), but are not considered to be clinically significant. For mandibular implants, at abutment connection the mean marginal bone level as measured from radiographs was 2.11 mm, and at follow-up was 2.02 mm. This slight gain in bone level was not statistically significant and is not considered to be clinically significant. CONCLUSIONS: Results of this prospective longitudinal study of implants placed into molar positions indicates favorable clinical outcomes. These CSR rates (91.5% mandibles, 82.9% maxillae) are less than what has been reported for implants placed into mandibular and maxillary anterior segments. Differences in outcomes between anterior and posterior locations may be related to bone quality and quantity.

Bone Density↗

Quantification of intact quadriceps tendon, quadriceps tendon insertion, and suprapatellar fat pad: MR arthrography, anatomy, and cryosections in the sagittal plane.

OBJECTIVE: The purpose of this study was to quantify quadriceps tendon length, thickness, and insertion in relation to the suprapatellar fat pad. SUBJECTS AND METHODS: We used three methods to analyze the anatomy of intact quadriceps tendons and insertions into the patellar base: MR arthrography (53 knees with intact extensor mechanisms), gross anatomy (16 cadaveric knees), and cryosections (four cadaveric knees). With an electronic cursor, two observers independently quantified the extensor mechanism on midline sagittal T1-weighted spin-echo sequences acquired on a low-field-strength (0.23 T) scanner. RESULTS: On MR arthrograms, quadriceps tendon length, determined from the superior patellar pole to the most superior part of the suprapatellar recess, measured 49 +/- 7 mm in women and 50 +/- 9 mm in men. Thickness of quadriceps tendon at three sites (suprapatellar recess, center, and superior patellar pole) measured 7 +/- 1 mm in women and 8 +/- 1 mm in men. Thickness was significantly larger in men at all measurement locations. Quadriceps tendon insertion and the suprapatellar fat pad along the patellar base measured 16 +/- 2 and 6 +/- 2 mm, respectively, in women, and 18 +/- 3 and 7 +/- 2 mm, respectively, in men. CONCLUSION: On midline MR images, sagittal thickness of the quadriceps tendon and its insertion was significantly larger in men than in women. The prevalence of the suprapatellar fat pad was 100%.

Adipose Tissue↗