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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 19 recordsLinked to original sources

Clinical evaluation of contrast-enhanced color Doppler sonography in the differential diagnosis of liver tumors.

PURPOSE: We investigated the value of contrast-enhanced color Doppler sonography in the differential diagnosis of liver tumors. METHODS: We prospectively examined 105 focal liver lesions in 100 patients by real-time gray-scale sonography, color Doppler sonography, and contrast-enhanced color Doppler sonography with galactose-based microbubbles (SH U 508A; Levovist). The final diagnoses of the liver lesions as confirmed by pathology or additional imaging techniques were 31 metastases, 25 hemangiomas, 19 hepatocellular carcinomas, 19 focal nodular hyperplasias, 2 cholangiocellular carcinomas, and 9 other lesions. RESULTS: Vascularity could be detected in 43 (41%) of the 105 lesions by conventional color Doppler sonography compared to 67 (64%) by contrast-enhanced color Doppler sonography. Contrast-enhanced color Doppler sonography identified moderate or extensive vascularity in all 19 focal nodular hyperplasias, moderate or extensive vascularity in 16 hepatocellular carcinomas and both cholangiocellular carcinomas, and no or minor vascularity in all but 3 hemangioma. The combination of gray-scale, conventional color Doppler, and contrast-enhanced color Doppler sonography led to the correct diagnosis in 81% of cases (85 of 105), compared to 57% (60/105) for gray-scale and conventional color Doppler sonography and 31% (33/105) for gray-scale sonography alone. CONCLUSIONS: Contrast-enhanced color Doppler sonography improves the detection of tumor vascularity and is useful in the differential diagnosis of liver lesions.

Confidence Intervals

Auxin-induced K+ channel expression represents an essential step in coleoptile growth and gravitropism.

Auxin-induced growth of coleoptiles depends on the presence of potassium and is suppressed by K+ channel blockers. To evaluate the role of K+ channels in auxin-mediated growth, we isolated and functionally expressed ZMK1 and ZMK2 (Zea mays K+ channel 1 and 2), two potassium channels from maize coleoptiles. In growth experiments, the time course of auxin-induced expression of ZMK1 coincided with the kinetics of coleoptile elongation. Upon gravistimulation of maize seedlings, ZMK1 expression followed the gravitropic-induced auxin redistribution. K+ channel expression increased even before a bending of the coleoptile was observed. The transcript level of ZMK2, expressed in vascular tissue, was not affected by auxin. In patch-clamp studies on coleoptile protoplasts, auxin increased K+ channel density while leaving channel properties unaffected. Thus, we conclude that coleoptile growth depends on the transcriptional up-regulation of ZMK1, an inwardly rectifying K+ channel expressed in the nonvascular tissue of this organ.

Animals

Evolution of the HOXB6 intergenic region: motif conservation at the lateral plate mesoderm (LPM) enhancer element.

This study reports the results of a comparative sequencing study in higher primates, focusing on the intergenic region located between HOXB6 and HOXB7. We have examined an 832 bp. region, encompassing a putative Lateral Plate Mesoderm (LPM) enhancer element in a variety of anthropoid apes. The interspecific comparisons reveal extensive substitutions occurring within this region, with a marked bias in favor of C-->T transitions within the enhancer element. The pattern of these substitutions suggests that the LPM enhancer region is subject to specific sequence and compositional constraints that are only revealed through comparative sequencing. These constraints produce an enhancer signature, the CpG microisland, which may be useful in identifying additional regulatory elements located within the HOX complexes. J. Exp. Zool. (Mol. Dev. Evol.) 285:170-176, 1999.

Animals

Channel-mediated high-affinity K+ uptake into guard cells from Arabidopsis.

Potassium uptake by higher plants is the result of high- or low-affinity transport accomplished by different sets of transporters. Although K+ channels were thought to mediate low-affinity uptake only, the molecular mechanism of the high-affinity, proton-dependent K+ uptake system is still scant. Taking advantage of the high-current resolution of the patch-clamp technique when applied to the small Arabidopsis thaliana guard cells densely packed with voltage-dependent K+ channels, we could directly record channels working in the concentration range of high-affinity K+ uptake systems. Here we show that the K+ channel KAT1 expressed in Arabidopsis guard cells and yeast is capable of mediating potassium uptake from media containing as little as 10 microM of external K+. Upon reduction of the external K+ content to the micromolar level the voltage dependence of the channel remained unaffected, indicating that this channel type represents a voltage sensor rather than a K+-sensing valve. This behavior results in K+ release through K+ uptake channels whenever the Nernst potential is negative to the activation threshold of the channel. In contrast to the H+-coupled K+ symport shown to account for high-affinity K+ uptake in roots, pH-dependent K+ uptake into guard cells is a result of a shift in the voltage dependence of the K+ channel. We conclude that plant K+ channels activated by acid pH may play an essential role in K+ uptake even from dilute solutions.

Journal Article

Gap junctions and connexin expression in the inner ear.

Several different recessive mutations in the connexin26 (Cx26; beta 2) gene have been associated with non-syndromic hereditary deafness. This suggests gap junctions are important to cochlear function. Numerous large gap junctions are present between adjacent supporting cells in both the vestibular and auditory sensory epithelia of the mature inner ear. In vestibular organs, Cx26 is highly expressed, but antibodies of Cx32 (beta 1) also label the supporting cells. In the organ of Corti of the cochlea, Cx26 is the predominant connexin isoform; neither Cx32 nor Cx43 (alpha 1) can be detected by immunohistochemistry. One role for gap junctions between supporting cells may be to provide a pathway for the rapid removal of ions away from the region of the sensory cells during transduction in order to maintain sensitivity. In the cochlea gap junctions are also associated with the basal cells of the stria vascularis, an ion-transporting epithelium that maintains a positive electrical potential in the potassium-rich endolymph fluid which bathes the apical surfaces of the sensory 'hair' cells and which is crucial for auditory transduction. Gap junctions are present between fibrocytes in the spiral ligament that underlies the stria vascularis, and between these fibrocytes and strial basal cells. During cochlear development, the initial formation and subsequent increase in size and number of gap junctions in the stria vascularis coincides with the initial generation and rise of the endocochlear potential. This and other evidence suggests that one role of gap junctions in the cochlea is to provide a pathway for passage of ions to maintain endolymph and, thus, auditory acuity. Mutations to Cx26 could, therefore, disrupt this ion circulation, resulting in deafness.

Amino Acid Sequence

Percutaneous ethanol injection and radio-frequency ablation for the treatment of nonresectable colorectal liver metastases - techniques and results.

BACKGROUND: Percutaneous ethanol injection (PEI) and radio-frequency (RF) ablation are possible palliative treatment modalities for patients with non-resectable liver metastases of colorectal carcinomas. The different techniques are explained and reviewed. RESULTS: PEI did not show promising results for the treatment of liver metastases. RF results were more encouraging; some studies showed improved mean survival times for patients when a complete necrosis of the metastases could be achieved. The maximum diameter of the necrotic area possible in a single session is about 5 cm. CONCLUSION: PEI and RF are palliative last-line treatment strategies for patients with non-resectable liver metastases and should only be applied if chemotherapy is not sufficient or not possible. The long-term efficacy of RF ablation in this group of patients has to be evaluated.

Catheter Ablation

Detection of increased tyrosine phosphorylation in murine Langerhans cells after stimulation with contact sensitizers.

The signalling pathways in epidermal Langerhans cells (LC) during activation by contact sensitizers are poorly understood. Recently, we have described an increased phosphorylation of tyrosine residues in human MHC class II-positive cells in vitro following stimulation with contact sensitizers. In the study reported here the formation of phosphotyrosine (p-tyr) in murine epidermal LC upon stimulation with contact sensitizers was examined. By the use of a flow cytometric technique a significant increase in p-tyr was demonstrated in LC stimulated in vitro with the strong contact sensitizers TNCB (2,4,6-trinitro-chlorobenzene) and MCI/MI (5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone) but not after treatment with the irritants sodium lauryl sulphate or benzoic acid. The protein tyrosine kinase inhibitors genistein and tyrphostin A9, but not tyrphostin AG 1288, were able to block this process significantly. Similar results were obtained using the LC-like dendritic cell line XS52. In addition, Western blot analysis on XS52 cells revealed a selective phosphorylation of two protein bands with a molecular weight between 50 and 60 kDa following stimulation with TNCB. These results demonstrate that contact sensitizers induce an increased phosphorylation of tyrosine residues in murine LC and can be used as the basis for in vivo studies using inhibitors for signal transduction pathways for prevention of primary sensitization to contact sensitizers.

Animals

The significance of high levels of lipoprotein (a) compared with established risk factors in premature coronary artery disease: differences between men and women.

It was shown in a series of studies that increased lipoprotein (a) concentration is a strong and independent risk factor for coronary artery disease. The goal of this study was to determine the significance of elevated lipoprotein (a) levels for the existence and the early manifestation of coronary artery disease by systematically recording cardiovascular risk factors in diagnostic coronary angiographies in a larger group of patients, whereby particular attention was paid to sex-specific differences. In 1011 consecutive patients who underwent coronary angiography (731 men, 280 women, mean age 59 +/- 10 years), fasting blood samples were taken immediately before the angiographies to determine the levels of cholesterol, low density lipoprotein-, high density lipoprotein-cholesterol, triglycerides and lipoprotein (a). In addition, further risk factors were qualitatively recorded. The data evaluation was carried out using the SPSSx software package univariately and multivariately with stepwise discriminant analysis. In 231 patients (144 men, 87 women) either no or only discrete coronary findings appeared, while in 780 cases (587 men, 193 women) coronary artery disease with stenoses > 50% were found. Women with coronary artery disease were significantly older than men and demonstrated higher lipoprotein levels. Women as well as men with coronary artery disease differed from healthy controls by having higher levels of lipoprotein (a) and other lipoproteins, lipoprotein (a) having the smallest error probability (P < 0.0005). The early manifestation of coronary artery disease (below the 18th age percentile) in men (< 50 years) was connected with significantly higher levels of cholesterol, triglycerides and lipoprotein (a), which emphasized their atherogenic significance in the general view. The most striking finding was that in young women (< 53 years), compared to older women with coronary artery disease--corresponding to the age-determined prevalence--significantly lower concentrations of cholesterol, triglycerides and lipoprotein (a) were found. Possible explanations include later manifestation of coronary artery disease, a steeper increase of the lipids with age, particularly of lipoprotein (a), but also a different valence of the risk factors in women.

Adult

Allergen-specific immune deviation from a TH2 to a TH1 response induced by dendritic cells and collagen type I.

BACKGROUND: Atopy and IgE production are associated with enhanced allergen-specific T(H)2 responses. Therefore a causative treatment may result from the deviation of this T(H)2-dominated immune response toward a T(H)1 response. OBJECTIVE: This study was carried out to analyze whether dendritic cells, the most potent antigen-presenting cells that are also known to induce antigen-specific T(H)1 responses, are suitable for therapy of atopic diseases by shifting the allergen-specific T(H)2 response toward a T(H)1 response. METHODS: Monocyte-derived dendritic cells were used to present allergens in vitro to autologous CD4(+) T cells of allergic persons. Because collagen type I activates dendritic cells and enhances the secretion of IL-12, we performed allergen presentation assays also in the presence of collagen type I. RESULTS: After stimulation with allergen-pulsed dendritic cells the production of IFN-gamma as well as that of IL-4 and IL-5 by CD4(+) T cells was enhanced. In the presence of collagen type I, however, a significant shift toward a T(H)1 response with increased production of IFN-gamma and a decreased production of IL-5 could be observed. When T cells were stimulated directly with anti-CD3 and anti-CD28 in the absence of antigen-presenting cells, it was demonstrated that collagen type I also exerted a direct effect on T cells, increasing their IFN-gamma production. CONCLUSION: These data indicate that collagen type I influences dendritic cells as well as T cells in a way that a shift in cytokine production results in a T(H)1 response even in already-sensitized atopic individuals.

Allergens

[Color doppler ultrasonographic detection of focal thyroid nodules].

AIM: To determine if colour Doppler sonography is a sensitive tool to detect solitary hot thyroid nodules. METHODS: All patients evaluated in our ultrasound laboratory during study period also underwent thyroid sonography. If one or more nodules with a diameter of at least 8 mm were present, thyroid scientigraphy was performed. Hyperperfusion within the nodule compared to the surrounding tissue indicated autonomy according to the study protocol. RESULTS: 1010 patients were screened. 385 had one or more nodules, 309 of them with a diameter of more than 8 mm. Among these patients a hot nodule was proved with scintigraphy in 120 cases. 116 of these 120 patients were correctly identified with colour Doppler sonography. CONCLUSION: Colour Doppler sonography is a reliable method to detect solitary hot or hyperperfused thyroid nodules and to identify a risk group of patients prior to the administration of x-ray contrast media.

Adult

On the accuracy of a new displacement instrumentation for rotary tablet presses.

The Portable Press Analyzer (PPA; Puuman Oy, Finland), a commercially available instrumentation for rotary tablet presses, was tested for accuracy of determination of force and displacement. The calibration of the force transducers (strain gauges) was tested under a static condition. The calibration of the displacement transducers (plastic film potentiometer) was compared for static and dynamic recordings. Force measurement was found precise (deviation < 1.1%) after alterations in the calibration procedure. Displacement measurement was affected by punch tilting and the application of the transducers. If tilting of punches was not considered, the deviation of displacement measurement from the true value (using steel tablets as a reference) was found up to 110 microns. By modifying the original PPA system by supplementing additional displacement transducers in the adjacent turret positions of the punches and adding a custom electronic device (Tilting Compensation Device), the accuracy of distance measurement was improved to 18.1 microns (+/- 3.64). Furthermore, machine and tooling deformation were recorded and found different under static and dynamic conditions. Correction of punch displacement for elastic deformation therefore should preferably be made from dynamic recordings.

Calibration

Reproducibility of irritant patch test reactions to sodium lauryl sulfate in a double-blind placebo-controlled randomized study using clinical scoring. Results from a study group of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).

Reading of doubtful patch test reactions can be improved by comparing them to defined negative, allergic and irritant controls. For the latter, an irritant patch test is needed that gives sufficiently reproducible results. In our double-blind, placebo-controlled, randomized study, we have analysed the synchronous reproducibility of patch tests with 0%, 0.0625%, 0.125%, 0.25%, 0.5% and 1.0% sodium lauryl sulfate (SLS). Tests and readings were done according to ESCD guidelines. 139 patients (75 women, 64 men) 18 to 77 years old were tested. The % of positive patients as well as the % of reproducible positive reactions increased with rising concentrations of SLS to a maximum of approximately 90% and 85%, respectively, with 1% SLS. Time courses of reactions were also related to the concentration of SLS: with 1% SLS, plateau-type time courses were most common (65%), followed by decrescendo- (23%) and crescendo-type reactions (12%). With 1% SLS, very similar mild to moderate reactions were obtained on days 2 and 3. The reaction threshold and reproducibility of tests were not related to age and sex of patients or to their own assessment of skin irritability. We conclude that 1% SLS is appropriate for an irritant patch test that gives sufficiently reproducible results.

Adolescent

Improved glycemic control reduces the impact of weight gain on cardiovascular risk factors in type 1 diabetes. The Epidemiology of Diabetes Complications Study.

OBJECTIVE: To assess the prevalence and incidence of being overweight in type 1 diabetes, to identify factors associated with weight gain and improved glycemic control, and to examine relationships among weight gain, glycemic control, and cardiovascular risk factors. RESEARCH DESIGN AND METHODS: The prevalence and incidence of being overweight in the Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort (n = 441) were compared with the general population (National Health and Nutrition Examination Survey [NHANES]). Factors associated with weight gain and improved glycemic control were identified, and relationships among weight gain, glycemic control, and cardiovascular risk factors were examined over a 6.9 +/- 2.2-year period. RESULTS: At baseline, the prevalence of being overweight (BMI > 27.8 kg/m2 for men and > 27.3 kg/m2 for women) was 10.4 and 11.4%, respectively, and was lower than the age- and sex-specific estimate for the general population (P < 0.05). The incidence of being overweight was comparable in men (12.6%) and women (11.8%) and did not differ from the general population (P = 0.98). Weight gain correlated with improvements in HbA1c (r = -0.21, P < 0.001). Patients with the highest baseline HbA1c levels gained the most weight and had the greatest improvement in glycemic control. A lower baseline BMI was also associated with a greater improvement in glycemic control. Weight gain favorably influenced the lipid profile in the setting of improved glycemic control, but adversely influenced the lipid profile in the absence of improved glycemic control. Weight change was directly associated with blood pressure change, but the incidence of hypertension was more strongly influenced by the development of nephropathy. CONCLUSIONS: The prevalence of being overweight in type 1 diabetes remains lower than that in the general population. Moderate weight gain did not adversely affect the cardiovascular risk profile in the setting of improved glycemic control.

Adult

Systemic interferon-alpha (IFN-alpha) treatment leads to Stat3 inactivation in melanoma precursor lesions.

BACKGROUND: In the setting of familial melanoma, the presence of atypical nevi, which are the precursors of melanoma, is associated with a nearly 100% risk of developing primary melanoma by age 70. In patients with sporadic melanoma, it is estimated that 40-60% of melanomas develop in contiguous association with atypical nevi. Currently, the only way to prevent atypical nevi from progressing to melanoma is to monitor and excise them as soon as they exhibit changes in their clinical features. Activation of the transcription factor, Stat3, has been linked to abnormal cell growth and transformation as well as to interferon alpha (IFN-alpha)-mediated growth suppression in vitro. MATERIALS AND METHODS: To determine whether IFN-alpha, used for adjuvant therapy of high-risk, resected melanoma, induces changes in Stat3 in atypical nevi, patients with a clinical history of melanoma who have multiple atypical nevi were treated for 3 months with low-dose IFN-alpha. Thereupon, the new technology of microscopic spectral imaging and biochemical assays such as electrophoretic mobility shift assays (EMSAs) and immunoblot analysis were used for the study of atypical nevi, obtained before and after IFN-alpha treatment. RESULTS: The results of the investigations provided evidence that, as a result of systemic IFN-alpha treatment, Stat1 and Stat3, which are constitutively activated in melanoma precursor lesions, lose their ability to bind DNA, and as shown in the case of Stat3, become dephosphorylated. CONCLUSIONS: Unlike primary and metastatic melanomas, melanoma precursor lesions cannot be established as cell cultures. Thus, the only way to explore pathways and treatment regimens that might help prevent progression to melanoma is within the context of a melanoma precursor lesion study conducted prospectively. The findings presented here suggest that down-regulation of the transcription factors Stat1 and Stat3 by systemic IFN-alpha treatment may represent a potential pathway to prevent the activation of gene(s) whose expression may be required for atypical nevus cells to progress to melanoma.

Aged

Absorbable fasteners for the fixation of ankle fractures.

Bioabsorbable materials have been used for the treatment of fractures for more than a century. We reviewed the results of a combined series of 30 ankle fractures from Bad Hersfeld, Germany, and Louisville, Kentucky, using initially polyglycolide and more recently poly-L-lactide screws and rods. The results were comparable to treatment with metal screws. The advantage of bioabsorbable implants is they do not need operations to take them out. There was a low incidence of reaction around the screw heads, which was reduced further with the use of the newer self-reinforced poly-L-lactate screws. The technique for use of plastics is different than the methods for placement of metal screws. Bioabsorbables will have an increasing role in fracture fixation in the future.

Absorbable Implants

Single mutations strongly alter the K+-selective pore of the K(in) channel KAT1.

Voltage-dependent potassium uptake channels represent the major pathway for K+ accumulation underlying guard cell swelling and stomatal opening. The core structure of these Shaker-like channels is represented by six transmembrane domains and an amphiphilic pore-forming region between the fifth and sixth domain. To explore the effect of point mutations within the stretch of amino acids lining the K+ conducting pore of KAT1, an Arabidopsis thaliana guard cell K(in) channel, we selected residues deep inside and in the periphery of the pore. The mutations on positions 256 and 267 strongly altered the interaction of the permeation pathway with external Ca2+ ions. Point mutations on position 256 in KAT1 affected the affinity towards Ca2+, the voltage dependence as well as kinetics of the Ca2+ blocking reaction. Among these T256S showed a Ca2+ phenotype reminiscent of an inactivation-like process, a phenomenon unknown for K(in) channels so far. Mutating histidine 267 to alanine, a substitution strongly affecting C-type inactivation in Shaker, this apparent inactivation could be linked to a very slow calcium block. The mutation H267A did not affect gating but hastened the Ca2+ block/unblock kinetics and increased the Ca2+ affinity of KAT1. From the analysis of the presented data we conclude that even moderate point mutations in the pore of KAT1 seem to affect the pore geometry rather than channel gating.

Animals

Spontaneous Ca2+ transients and their transmission in the developing chick retina.

The development of the central nervous system is dependent on spontaneous action potentials and changes in [Ca2+]i occurring in neurons [1-4]. In the mammalian retina, waves of spontaneous electrical activity spread between retinal neurons, raising [Ca2+]i as they pass [5-7]. In the ferret retina, the first spontaneous Ca2+ waves have been reported at postnatal day 2 and are thought to result from the Ca2+ influx associated with bursts of action potentials seen in ganglion cells at this time [5-7]. These waves depend on depolarisation produced by voltage-gated sodium channels, but their initiation and/or propagation also depends upon nicotinic cholinergic synaptic transmission between amacrine cells and ganglion cells [8]. Here, we report contrasting results for the chick retina where Ca2+ transients are seen at times before retinal synapse formation but when there are extensive networks of gap junctions. These Ca2+ transients do not require nicotinic cholinergic transmission but are modulated by acetylcholine (ACh), dopamine and glycine. Furthermore, they propagate into the depth of the retina, suggesting that they are not restricted to ganglion and amacrine cells. The transients are abolished by the gap-junctional blocker octanol. Thus, the Ca2+ transients seen early in chick retinal development are triggered and propagate in the absence of synapses by a mechanism that involves several neurotransmitters and gap junctions.

Acetylcholine