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Biomedical subjects

D Becker

Publications and source records attributed to D Becker.

At least 55 records · Page 3Linked to original sources
PubMed2001

Applications of spectral imaging: detection and analysis of human melanoma and its precursors.

Light-based imaging has extensive applications for medicine and biology, and recent advances in optical imaging modalities, such as confocal and multi-photon scanning fluorescence microscopy, bioluminescence, optical coherence tomography, and spectral imaging, have opened new avenues for visualizing and recording over time dynamic changes in genetic, developmental, and disease mechanisms that cannot be captured by conventional light microscopy. In the present article, we focus on spectral imaging, and using human melanoma and its precursor lesions as an example, we describe the ability of spectral imaging to detect early-stage disease, capture gene expression profiles in tissue specimens, and visualize gene functions in tumors growing in living animals.

Animals↗
PubMed2001

[Harmonic imaging for improving diagnosis of liver tumors--preliminary report].

UNLABELLED: Contrast harmonic imaging (CHI) is a new Doppler technology using the non-linear properties of ultrasound contrast agents. AIM: In this pilot study contrast harmonic imaging was evaluated for the detection and characterization of liver lesions. METHODS: Tumor vascularity patterns and diagnostic accuracy in the differential diagnosis of liver lesions were compared in 50 liver lesions using gray-scale sonography, unenhanced and enhanced power Doppler sonography and CHI. In addition, CHI was compared to spiral-CT for the detection of liver metastases in 28 patients. RESULTS: CHI was superior to power Doppler sonography in the visualization of vascularity pattern. Due to the better resolution and image quality of tumor vascularity the diagnostic accuracy of CHI in the differential diagnosis of liver lesions was higher (88% CHI versus 40% unenhanced power Doppler, and 58% contrast-enhanced power Doppler). In the detection of liver metastasis CHI showed a higher sensitivity (96.8%) compared to spiral-CT (74.6%) in 28 patients with 63 metastases. CONCLUSIONS: CHI is a promising new ultrasound technology to further improve the differential diagnosis of liver lesions and the detection of metastases.

Albumins↗
PubMed2001

Echo-enhanced color- and power-Doppler EUS for the discrimination between focal pancreatitis and pancreatic carcinoma.

BACKGROUND: EUS is a precise method for detection and staging of pancreatic tumors. However, differentiation between inflammatory pseudotumor and pancreatic carcinoma remains difficult. The aim of this study was to evaluate contrast-enhanced EUS as a method of differentiating inflammation and carcinoma based on perfusion characteristics. METHODS: Patients with solid pancreatic masses underwent EUS with a linear echoendoscope. Perfusion in the pancreatic tissue and the mass was assessed with native and contrast-enhanced EUS with power- and color-Doppler imaging. Examinations were evaluated by a blinded reader. A markedly hyperperfused lesion was considered an inflammatory pseudotumor whereas lesions that were hypoperfused compared with surrounding tissue were considered to be carcinoma. RESULTS: Fifteen of 23 patients had hypoperfusion within the mass and 8 patients had hyperperfused lesions. Of the 15 patients with hypoperfused masses, all had pancreatic adenocarcinoma; 1 of 8 patients with a hyperperfused lesion also had adenocarcinoma. The remaining 7 patients had focal inflammation. Sensitivity for differentiation of pancreatic carcinoma versus inflammatory changes was 94%, specificity 100%. CONCLUSION: Echo-enhanced power-Doppler EUS reliably differentiates pancreatic neoplasm and focal pancreatitis. The diagnostic accuracy of this technique is comparable to CT, magnetic resonance imaging, positron emission tomography, and ERCP.

Adenocarcinoma↗
PubMed2001

Properties of fujicalin, a new modified anhydrous dibasic calcium phosphate for direct compression: comparison with dicalcium phosphate dihydrate.

The novel, commercially available, free-flowing spherically granulated dicalcium phosphate anhydrous (SGDCPA) Fujicalin for direct tableting was compared with directly compressible dicalcium phosphate dihYdrate (DCPD), the properties of which are well known. The two excipients were investigated and compared with regard to their physical and powder properties, compressibility, and compactibility. As a consequence of the spherical shape of its particles, SGDCPA shows the same good flowability and even better compactibility. In contrast to DCPD, SGDCPA shows significant uptake of moisture when exposed to relative humidities (RHs) exceeding 70%. For both excipients, the main deformation mechanism is fragmentation, with SGDCPA yielding significantly stronger tablets.

Calcium Phosphates↗
PubMed2001

Heterologous expression of genes mediating enhanced fungal resistance in transgenic wheat.

Three cDNAs encoding the antifungal protein Ag-AFP from the fungus Aspergillus giganteus, a barley class II chitinase and a barley type I RIP, all regulated by the constitutive Ubiquitin1 promoter from maize, were expressed in transgenic wheat. In 17 wheat lines, stable integration and inheritance of one of the three transgenes has been demonstrated over four generations. The formation of powdery mildew (Erysiphe graminis f. sp. tritici) or leaf rust (Puccinia recondita f. sp. tritici) colonies was significantly reduced on leaves from afp or chitinase II- but not from rip I-expressing wheat lines compared with non-transgenic controls. The increased resistance of afp and chitinase II lines was dependent on the dose of fungal spores used for inoculation. Heterologous expression of the fungal afp gene and the barley chitinase II gene in wheat demonstrated that colony formation and, thereby, spreading of two important biotrophic fungal diseases is inhibited approximately 40 to 50% at an inoculum density of 80 to 100 spores per cm2.

Animals↗
PubMed2001

The pore of plant K(+) channels is involved in voltage and pH sensing: domain-swapping between different K(+) channel alpha-subunits.

Plant K(+) uptake channel types differ with respect to their voltage, Ca(2)+, and pH dependence. Here, we constructed recombinant chimeric channels between KST1, a member of the inward-rectifying, acid-activated KAT1 family, and AKT3, a member of the weakly voltage-dependent, proton-blocked AKT2/3 family. The homologous pore regions of AKT3 (amino acids 216 to 287) and KST1 (amino acids 217 to 289) have been exchanged to generate the two chimeric channels AKT3/(p)KST1 and KST1/(p)AKT3. In contrast to AKT3 wild-type channels, AKT3/(p)KST1 revealed a strong inward rectification reminiscent of that of KST1. Correspondingly, the substitution of the KST1 by the AKT3 pore led to less pronounced rectification properties of KST1/(p)AKT3 compared with wild-type KST1. Besides the voltage dependence, the interaction between the chimera and extracellular H(+) and Ca(2)+ resembled the properties of the inserted rather than the respective wild-type pore. Whereas AKT3/(p)KST1 was acid activated and Ca(2)+ insensitive, extracellular protons and Ca(2)+ inhibited KST1/(p)AKT3. The regulation of the chimeric channels by cytoplasmic protons followed the respective wild-type backbone of the chimeric channels, indicating that the intracellular pH sensor is located outside the P domain. We thus conclude that essential elements for external pH and Ca(2)+ regulation and for the rectification of voltage-dependent K(+) uptake channels are located within the channel pore.

Amino Acid Sequence↗
PubMed2001

Family therapy with unmarried African American mothers and their adolescents.

Almost two-thirds of African American births are to unmarried mothers, and these single parents are among the most economically vulnerable in the United States. The effects of chronic stressors such as poverty can compromise the ability of these mothers to parent effectively, particularly during the developmental period of adolescence, typically a stressful phase of parenting. This article describes a multidimensional family therapy (MDFT) approach to working with African American adolescents who have drug and/or behavior problems. It is maintained that addressing the intrapersonal functioning of African American single mothers is vital if they are to re-establish the attachment bonds necessary for the maintenance of essential parental influence in the lives of their adolescents. Through systematic attention to the parent as an individual, leading to a balance between self-care and care for others, parental supervision is more easily achieved and relational impasses between parent and adolescent more equitably resolved.

Adolescent↗
PubMed2001

Mortality trends in type 1 diabetes. The Allegheny County (Pennsylvania) Registry 1965-1999.

OBJECTIVES: To investigate long-term mortality and its temporal trends as of 1 January 1999 among the 1,075 patients with type 1 diabetes (onset age <18 years, diagnosed between 1965 and 1979) who comprise the Allegheny County population-based registry. RESEARCH DESIGN AND METHODS: Overall, sex- and race-specific mortality rates per person-year of follow-up were determined. Standardized mortality ratios were also calculated. Survival analyses and Cox proportional hazard model were also used. Temporal trends were examined by dividing the cohort into three groups by year of diagnosis (1965-1969, 1970-1974, and 1975-1979). RESULTS: Living status of 972 cases was ascertained as of January 1, 1999 (ascertainment rate 90.4%). The mean duration of diabetes was 25.2 +/- 5.8 (SD) years. Overall, 170 deaths were observed. The crude mortality rate was 627 per 100,000 person-years (95% CI 532-728) and standardized mortality ratio was 519 (440-602). Life-table analyses by the Kaplan-Meier method indicated cumulative survival rates of 98.0% at 10 years, 92.1% at 20 years, and 79.6% at 30 years duration of diabetes. There was a significant improvement in the survival rate between the cohort diagnosed during 1965-1969 and that diagnosed during 1975-1979 by the log-rank test (P = 0.03). Mortality was higher in African-Americans than in Caucasians, but there were no differences seen by sex. The improvement in recent years was seen in both ethnic groups and sexes. CONCLUSIONS: An improvement in long-term survival was observed in the more recently diagnosed cohort. This improvement is consistent with the introduction of HbA1 testing, home blood glucose monitoring, and improved blood pressure therapy in the 1980s.

Adult↗
PubMed2001

Use of pIRES vectors to express EGFP and connexin constructs in studies of the role of gap junctional communication in the early development of the chick retina and brain.

Control of cell proliferation is vital for the normal development of the neural retina. Gap junctional communication has been implicated in the control of retinal cell proliferation. We have previously shown that the expression of the gap junction protein Connexin 43 closely correlates with the first wave of cell proliferation in the retina. Preventing its expression using antisense oligonucleotides in the developing eye and surrounding tissues, produces a reduction in cell number and the formation of a small eye. In order to examine this in more detail we have developed a new means of manipulating connexin expression in the developing chick embryo. We have generated pIRES vectors which use cyclomegalovirus (CMV) to promote the expression of a green fluorescent protein (EGFP) and either wild type Cx43 or a dominant negative form ofthis connexin. Following injection ofthese constructs into the ventricles ofthe stage 10-11 chick embryo they can be incorporated into one side of the chick brain or optic vesicle using an electroporation technique, leaving the other side as a control. EGFP expression can be seen on the electroporated side of the chick brain within 24 hours. Expression of the dominant negative construct in cultures of chick limb bud mesenchyme results in total block of cascade blue transfer when injected into transfected cells. Expression of both wild type and dominant negative constructs in the developing chick retina perturbs the normal development of the eye.

Animals↗
PubMed2001

Detection of liver metastases: comparison of contrast-enhanced wide-band harmonic imaging with conventional ultrasonography.

OBJECTIVE: To compare the detection rate of conventional ultrasonography and contrast-enhanced wide-band harmonic ultrasonographic imaging in the detection of small liver metastases. METHODS: Consecutive patients with histologically proved gastrointestinal carcinoma liver metastases were studied. Biphasic helical computed tomography, conventional ultrasonography, and contrast-enhanced wide-band harmonic imaging were performed on all patients within a 5-day period. The biphasic helical computed tomographic scans were reviewed and interpreted by a skilled radiologist. The number of lesions and their descriptive characteristics were recorded for analysis. In addition, videotape recordings of the conventional ultrasonography and contrast-enhanced wide-band harmonic imaging were blindly reviewed, after which the number of detected lesions and their characteristics were then compared with those detected on biphasic helical computed tomography, considered the standard of reference. RESULTS: Twenty-eight patients (10 female and 18 male; age range, 45-72 years) were studied. Conventional ultrasonography detected 37 (59%) of all lesions visualized by biphasic helical computed tomography. The detection rate for contrast-enhanced wide-band harmonic imaging was significantly higher (61 [97%] of 63). In our series, two 10-mm lesions near the diaphragm were not visualized by wide-band harmonic imaging. CONCLUSIONS: The use of contrast-enhanced imaging techniques significantly improves the ultrasonographic detection of liver metastases. Our results achieved the sensitivity of biphasic helical computed tomography.

Aged↗
PubMed2001

VFK1, a Vicia faba K(+) channel involved in phloem unloading.

In search of a K(+) channel involved in phloem transport we screened a Vicia faba cotyledon cDNA library taking advantage of a set of degenerated primers, flanking regions conserved among K(+) uptake channels. We cloned VFK1 (for Vicia faba K(+) channel 1) characterised by a structure known from the Shaker family of plant K(+) channels. When co-expressed with a KAT1 mutant in Xenopus oocytes, heteromers revealed the biophysical properties of a K(+) selective, proton-blocked channel. Northern blot analyses showed high levels of expression in cotyledons, flowers, stem and leaves. Using in situ PCR techniques we could localise the K(+) channel mRNA in the phloem. In the stem VFK1 expression levels were higher in the lower internodes. There channel transcripts increased in the light and thus under conditions of increased photosynthate allocation. VFK1 transcripts are elevated in sink leaves, and rise in source leaves during the experimental transition into sinks. Fructose- rather than sucrose- or glucose-feeding via the petiole induced VFK1 gene activity. We therefore monitored the fructose sensitivity of the sieve tube potential through cut aphid stylets. In response to an 1 h fructose treatment the sieve tube potential shift increased from 19 mV to 53 mV per 10-fold change in K(+) concentration. Under these conditions K(+) channels dominated the electrical properties of the plasma membrane. Based on the phloem localisation and expression patterns of VFK1 we conclude that this K(+) channel is involved in sugar unloading and K(+) retrieval.

Amino Acid Sequence↗
PubMed2001

Beta-blockers: a new therapy in congestive heart failure.

BACKGROUND: Until recently, use of beta-blockers was contraindicated in treatment of patients with congestive heart failure. However, empirical evidence suggests that adding beta-blockers to the standard therapy can slow the progression of heart failure and reduce mortality, including sudden cardiac death. PURPOSE: To analyze the results of major, prospective, randomized controlled trials on the effects of beta-blockers in congestive heart failure and to provide recommendations for clinical practice and patients' education. METHODS: MEDLINE (1989-2001) and biomedical databases (1995-2001) were searched for literature on the use of beta-blockers in patients with congestive heart failure. Information on major randomized controlled trials of at least 6 months' duration with mortality as a major end point were reviewed. RESULTS: Both selective and nonselective beta-blockers significantly reduce mortality due to all causes; decrease need for hospitalization due to cardiovascular causes; and improve patients' New York Heart Association functional classification, hemodynamic status, left ventricular ejection fraction, and signs and symptoms of congestive heartfailure. However, clinical use of beta-blockers remains limited. CONCLUSION: Strong empirical evidence supports adding beta-blockers to the standard therapy for congestive heart failure. Future efforts should be directed toward establishing the safety and efficacy of beta-blockers in patients with severe heartfailure.

Adrenergic beta-Antagonists↗
PubMed2001

[Effects of the physical configuration of plasmid DNA and other factors on production of fertile transgenic wheat plants].

The applicability of hyperosmotic treatment and different configurations of plasmid DNA for stable transformation of wheat mediated by particle bombardment was investigated. Hyperosmotic treatment increased the frequency of transient expression and had also a positive effect on stable transformation. Denaturation of plasmid DNA prior to bombardment led to dramatic reduction of transient expression. However, there were no marked differences between single-stranded and double-stranded DNA in stable transformation. Single-stranded plasmid DNA, double-stranded plasmid DNA in linear state and double-stranded plasmid DNA in circular state could all be used to produce transgenic wheat plants. A total of 26 independent transgenic plants of winter wheat genotype Florida and 4 independent transgenic plants of spring wheat genotype Veery were obtained. Most transgenic plants have set seeds. T2 seeds of some spring wheat transgenic plants have also been harvested.

Aminobutyrates↗
PubMed2000

GORK, a delayed outward rectifier expressed in guard cells of Arabidopsis thaliana, is a K(+)-selective, K(+)-sensing ion channel.

Here we report on the molecular identification, guard cell expression and functional characterization of AtGORK, an Arabidopsis thaliana guard cell outward rectifying K(+) channel. GORK represents a new member of the plant Shaker K(+) channel superfamily. When heterologously expressed in Xenopus oocytes the gene product of GORK mediated depolarization-activated K(+) currents. In agreement with the delayed outward rectifier in intact guard cells and protoplasts thereof, GORK is activated in a voltage- and potassium-dependent manner. Furthermore, the single channel conductance and regulation of GORK in response to pH changes resembles the biophysical properties of the guard cell delayed outward rectifier. Thus GORK very likely represents the molecular entity for depolarization-induced potassium release from guard cells.

Animals↗
PubMed2000

[Enhanced imaging diagnosis of liver carcinomas. Technical progress is not a substitute for clinical knowledge].

Cholangiocellular carcinomas (CCCs) of the peripheral type (not Klatskin tumors) appear sonographically as solid space-occupying lesions. No typical sonomorphological signs are known. Important hint for the clinician is the knowledge of earlier or accompanying diseases in which CCCs occur more often (primary sclerosing cholangitis, ulcerative colitis, intrahepatic gallstones, parasitic diseases of the bile ducts, choledochal cysts, Caroli's syndrome). Typical Color-Doppler signs are also missing. Definitive diagnostic is left to biopsy. Hepatocellular carcinomas (HCCs) mostly occur in cirrhotic livers. Every newly detected space-occupying lesion in a cirrhotic liver is suspected of HCC until otherwise proven, even when AFP-levels are normal. AFP levels constantly higher than 400 ng/ml make HCC probable, AFP levels of 2000 ng/ml ore more proof HCC. Gray-scale imaging is not uniform and not guiding. Using Color-Doppler nearly all HCCs show markedly hyperperfusion compared to the surrounding liver tissue, vessels are arranged in a chaotic shape. Echo-enhanced Color-Doppler always shows a distinct early arterial hyperperfusion.

Bile Duct Neoplasms↗
PubMed2000

Hydrolyses of alpha- and beta-cellobiosyl fluorides by Cel6A (cellobiohydrolase II) of Trichoderma reesei and Humicola insolens.

We have measured the hydrolyses of alpha- and beta-cellobiosyl fluorides by the Cel6A [cellobiohydrolase II (CBHII)] enzymes of Humicola insolens and Trichoderma reesei, which have essentially identical crystal structures [Varrot, Hastrup, Schülein and Davies (1999) Biochem. J. 337, 297-304]. The beta-fluoride is hydrolysed according to Michaelis-Menten kinetics by both enzymes. When the approximately 2.0% of beta-fluoride which is an inevitable contaminant in all preparations of the alpha-fluoride is hydrolysed by Cel7A (CBHI) of T. reesei before initial-rate measurements are made, both Cel6A enzymes show a sigmoidal dependence of rate on substrate concentration, as well as activation by cellobiose. These kinetics are consistent with the classic Hehre resynthesis-hydrolysis mechanism for glycosidase-catalysed hydrolysis of the 'wrong' glycosyl fluoride for both enzymes. The Michaelis-Menten kinetics of alpha-cellobiosyl fluoride hydrolysis by the T. reesei enzyme, and its inhibition by cellobiose, previously reported [Konstantinidis, Marsden and Sinnott (1993) Biochem. J. 291, 883-888] are withdrawn. (1)H NMR monitoring of the hydrolysis of alpha-cellobiosyl fluoride by both enzymes reveals that in neither case is alpha-cellobiosyl fluoride released into solution in detectable quantities, but instead it appears to be hydrolysed in the enzyme active site as soon as it is formed.

Allosteric Regulation↗
PubMed2000

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↗