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Biomedical subjects

D Beck

Publications and source records attributed to D Beck.

At least 19 recordsLinked to original sources
PubMed2006

Vanilla mosaic virus isolates from French Polynesia and the Cook Islands are Dasheen mosaic virus strains that exclusively infect vanilla.

Sequence was determined for the coat protein (CP) gene and 3' non-translated region (3'NTR) of two vanilla mosaic virus (VanMV) isolates from Vanilla tahitensis, respectively from the Cook Islands (VanMV-CI) and French Polynesia (VanMV-FP). Both viruses displayed distinctive features in the N-terminal region of their CPs; for VanMV-CI, a 16-amino-acid deletion including the aphid transmission-related DAG motif, and for VanMV-FP, a stretch of GTN repeats that putatively belongs to the class of natively unfolded proteins. VanMV-FP CP also has a novel DVG motif in place of the DAG motif, and an uncommon Q//V protease cleavage site. The sequences were compared to a range of Dasheen mosaic virus (DsMV) strains and to potyviruses infecting orchids. Identity was low to DsMV strains across the entire CP coding region and across the 3'NTR, but high across the CP core and the CI-6K2-NIa region. In accordance with current ICTV criteria for species demarcation within the family Potyviridae, VanMV-CI and VanMV-FP are strains of DsMV that exclusively infect vanilla.

3' Untranslated Regions↗
PubMed2004

Mass measurement on the rp-process waiting point 72Kr.

The mass of one of the three major waiting points in the astrophysical rp process 72Kr was measured for the first time with the Penning trap mass spectrometer ISOLTRAP. The measurement yielded a relative mass uncertainty of deltam/m=1.2x10(-7) (deltam=8 keV). (73,74)Kr, also needed for astrophysical calculations, were measured with more than 1 order of magnitude improved accuracy. We use the ISOLTRAP masses of 72-74Kr to reanalyze the role of 72Kr (T(1/2)=17.2 s) in the rp process during x-ray bursts and conclude that 72Kr is a strong waiting point delaying the burst duration with at least 80% of its beta-decay half-life.

Journal Article↗
PubMed2004

The mass of 22Mg.

Mass measurements with a relative precision of better than 1.5 x 10(-8) were performed on 22Mg and its reaction partners 21Na and 22Na with the ISOLTRAP Penning trap mass spectrometer at CERN, yielding the mass excesses D(22Mg)=-399.92(27) keV, D(21Na)=-2184.71(21) keV, and D(22Na)=-5181.56(16) keV. The importance of these results is twofold. First, a comparative half-life (Ft value) has been obtained for the superallowed beta decay of 22Mg to further test the conserved-vector-current hypothesis. Second, the resonance energy for the 21Na proton capture reaction has been independently determined, allowing direct comparisons of observable gamma radiation in nova explosions with the yield expected from models.

Journal Article↗
PubMed2004

Direct mass measurements on the superallowed emitter 74Rb and its daughter 74Kr: isospin-symmetry-breaking correction for standard-model tests.

The decay energy of the superallowed beta decay 74Rb(beta+)74Kr was determined by direct Penning trap mass measurements on both the mother and the daughter nuclide using the time-of-flight resonance technique and was found to be Q=10 416.8(4.5) keV. The exotic nuclide 74Rb, with a half-life of only 65 ms, is the shortest-lived nuclide on which a high-precision mass measurement in a Penning trap has been carried out. Together with existing data for the partial half-life as well as theoretical corrections, the decay energy yields a comparative half-life of Ft=3084(15) s for this decay, in agreement with the mean value for the series of the lighter nuclides from 10C to 54Co. Assuming conserved vector current, this result allows for an experimental determination of the isospin-symmetry-breaking correction deltaC.

Journal Article↗
PubMed2004

Unambiguous identification of three beta-decaying isomers in 70Cu.

Using resonant laser ionization, beta-decay studies, and for the first time mass measurements, three beta-decaying states have been unambiguously identified in 70Cu. A mass excess of -62 976.1(1.6) keV and a half-life of 44.5(2) s for the (6-) ground state have been determined. The level energies of the (3-) isomer at 101.1(3) keV with T(1/2)=33(2) s and the 1+ isomer at 242.4(3) keV with T(1/2)=6.6(2) s are confirmed by high-precision mass measurements. The low-lying levels of 70Cu populated in the decay of 70Ni and in transfer reactions compare well with large-scale shell-model calculations, and the wave functions appear to be dominated by one proton-one neutron configurations outside the closed Z=28 shell and N=40 subshell. This does not apply to the 1+ state at 1980 keV which exhibits a particular feeding and deexcitation pattern not reproduced by the shell-model calculations.

Journal Article↗
PubMed2003

Masses of 32Ar and 33Ar for fundamental tests.

Masses of the short-lived radionuclides 32Ar (T(1/2)=98 ms) and 33Ar (T(1/2)=173 ms) have been determined with the Penning trap mass spectrometer ISOLTRAP. Relative uncertainties of 6.0x10(-8) (deltam=1.8 keV) and 1.4x10(-8) (deltam=0.44 keV), respectively, have been achieved. At present, these new mass data serve as the most stringent test of the quadratic form of the isobaric-multiplet mass equation. Furthermore, the improved accuracy for the mass of 32Ar will allow for a better constraint on scalar contributions to the weak interaction. New mass values have also been measured for 44Ar and 45Ar, and a 20sigma deviation for 44Ar from the literature value was found and interpreted.

Journal Article↗
PubMed2003

Use of SSRs for establishing heterotic groups in subtropical maize.

Heterotic groups and patterns are of fundamental importance in hybrid breeding. The objectives of our research were to: (1) investigate the relationship of simple sequence repeats (SSR) based genetic distances between populations and panmictic midparent heterosis (PMPH) in a broad range of CIMMYT maize germplasm, (2) evaluate the usefulness of SSR markers for defining heterotic groups and patterns in subtropical germplasm, and (3) examine applications of SSR markers for broadening heterotic groups by systematic introgression of other germplasm. Published data of two diallels and one factorial evaluated for grain yield were re-analyzed to calculate the PMPH in population hybrids. Additionally, 20 pools and populations widely used in CIMMYT's breeding program were assayed with 83 SSR markers covering the entire maize genome. Correlations of squared modified Roger's distance (MRD(2)) and PMPH were mostly positive and significant, but adaption problems caused deviations in some cases. For intermediate- and early-maturity subtropical germplasm, two heterotic groups could be suggested consisting of a flint and dent composite. We concluded that the relationships between the populations obtained by SSR analyses are in excellent agreement with pedigree information. SSR markers are a valuable complementation to field trials for identifying heterotic groups and can be used to introgress exotic germplasm systematically.

Alleles↗
PubMed2001

Breakdown of the isobaric multiplet mass equation at A = 33, T = 3/2.

Mass measurements on (33,34,42,43)Ar were performed using the Penning trap mass spectrometer ISOLTRAP and a newly constructed linear Paul trap. This arrangement allowed us, for the first time, to extend Penning trap mass measurements to nuclides with half-lives below one second ( 33Ar: T(1/2) = 174 ms). A mass accuracy of about 10(-7) (deltam approximately 4 keV) was achieved for all investigated nuclides. The isobaric multiplet mass equation was checked for the A = 33, T = 3/2 quartet and found to be inconsistent with the generally accepted quadratic form.

Journal Article↗
PubMed2001

[Symptom control in palliative medicine].

Palliative medicine has as its goal improving the quality of life of patients with incurable diseases and their family members. According to the WHO, alleviating pain and other physical symptoms, as well as addressing psycho-social and spiritual problems have the highest priority. The role of medicine and the physician is inseparably linked to psycho-social and nursing resources in a multi-disciplinary team. Advanced stages of cancer are particularly characterized by symptoms which can cause lasting impairment of normal life. In addition to pain, patients suffer from other, often extremely distressing physical symptoms such as constipation, nausea and vomiting, gastrointestinal obstruction and difficulty in breathing. The first priority is to determine the causes of the individual symptoms, since therapeutic decisions are based on the specific pathophysiological mechanisms. Effective symptom management presupposes exact knowledge of the pharmacokinetics. The often difficult decision between causal and symptomatic therapy options must - whenever possible - be made together with the patient and frequently in interdisciplinary medical consultation. Tumor pain therapy follows the guidelines of the World Health Organization. Crucial are long-term therapy and dose titration of the analgesics, stepped progression between the groups of medication, and specific therapy approaches for neuropathic pain components. The significance of constipation with its variety of possible complications is often underestimated in the context of the tumor patient. Effective prophylaxis and cause-based therapy do improve the nutritional care and can help to prevent the transition to an ileus. New findings concerning the role of neurotransmitters in triggering nausea and vomiting have opened up specific methods of attack. Dyspnoea therapy places high demands on the medical team, since nursing measures must effectively supplement the more limited medical possibilities.

Humans↗
PubMed2001

Membrane activity of (Cys48Ser) lung surfactant protein B increases with dimerisation.

One of the possible functions of lung surfactant protein B (SP-B), an hydrophobic membrane-associated saposin-like protein, is to reduce the alveolar surface tension by promoting insertion of phospholipids into the air/liquid interface of the lung. SP-B is a covalent homodimer; Cys48 of two polypeptides form an intermolecular disulphide bond. In order to test whether dimerisation of SP-B is important for surfactant function, transgenic mice which express (Cys48Ser) human SP-B in a mouse SP-B null background were generated. In previous studies (Cys48Ser)SP-B showed a concentration-dependent in vitro activity, suggesting that it may form non-covalent dimers. Here (Cys48Ser)SP-B isolated from bronchoalveolar lavage of transgenic mice was studied at different concentrations by circular dichroism (CD) spectroscopy, pulsating bubble surfactometry, mass spectrometry and reversed-phase HPLC. The results indicate that (Cys48Ser)SP-B, both in a phospholipid environment and in organic solvents, is largely monomeric and exhibits low activity at concentrations lower than 1 -2 microM, while at higher concentrations it forms non-covalent dimers, which are nearly functionally equivalent to native SP-B in vitro. Furthermore, electrospray mass spectrometry showed that more dimers were found relative to the monomer when the polarity of the solvent was decreased, and when the concentration of SP-B increased. (Cys48Ser)SP-B also eluted earlier than native SP-B in reversed-phase HPLC. Taken together, these results indicate that a polar surface is buried upon dimerisation, thereby promoting formation of interchain ion pairs between Glu51-Arg52' and Glu51'-Arg52.

Amino Acid Substitution↗
PubMed2000

The diagnostic value of power Doppler measurements in the endometrium of women with postmenopausal bleeding.

OBJECTIVE: The objective was to evaluate the accuracy of blood flow measurements by power Doppler in endometrial vessels in women with postmenopausal bleeding (PMB). METHODS: Sixty consecutive patients with PMB participated in the study. Endometrial thickness and power Doppler measurements of small vessels in the endometrium and subendometrial tissue were performed prior to dilatation and curettage. Correlation between Doppler indices, endometrial thickness (by transvaginal sonography), and histopathologic examination was performed. A Student t test was used for statistical analysis with P < 0.05 as the level of significance. RESULTS: Fourteen positive cases were found: 11 endometrial cancers, 1 sarcoma, 1 simple hyperplasia, and 1 complex hyperplasia with atypia. Measurements of endometrial thickness using a cutoff point of 5 mm revealed a sensitivity of 78% and specificity of 45.6% (P > 0.05, NS) for detecting endometrial pathology. Power Doppler measurements (pulsatility index cutoff point = 1.0) revealed a sensitivity of 85. 7% and specificity of 89% (P = 0.001) for detecting endometrial pathology. CONCLUSIONS: The noninvasive methods for endometrial evaluation are not sensitive enough to exclude endometrial pathology. When invasive methods could not be performed, the combination of transvaginal sonography and power Doppler imaging provided the best results. When both modalities are negative, the probability of cancer is less than 5%.

Adult↗
PubMed2000

Patients with double primary tumors in the breast and ovary- clinical characteristics and BRCA1-2 mutations status.

OBJECTIVE: The aim of this study was to define the prevalence, clinical characteristics, and BRCA1-2 mutation carrier status of ovarian cancer (OvC) patients with a previous primary malignancy in the breast (PPMBr). METHODS: The study population comprised 1240 consecutive Jewish Israeli women with pathologically confirmed epithelial OvC diagnosed between March 1, 1994, and December 31, 1997. Demographic and clinical data were obtained from medical files and from a detailed questionnaire taken through a nationwide epidemiological case-control study on OvC. Blood samples and tumor tissues were collected for analysis of the three predominant germline BRCA1-2 Jewish founder mutations (185delAG, 5382insC, and 6174delT). RESULTS: Fifty nine (4.7%) patients with OvC had a PPMBr. The median age at diagnosis of OvC was 60 years. The mean interval between the two diagnoses was 104 months (range 0-363 months). In the majority of the patients (n = 53), the diagnosis of breast cancer (BrC) preceded the OvC by more than 1 year. The ovarian tumors were diagnosed in 47% of the cases following investigation of patients' symptoms. In 41%, diagnosis was made as a consequence of check-up exams performed during the routine follow-up of BrC survivors. Patients with PPMBr were more likely to present with FIGO ovarian stage III-IV, compared to women with solitary OvC (73% vs 60. 3%, P < 0.05), and less likely to have borderline tumors (3.4% vs 17. 9%, P = 0.007). Family history of OvC/BrC was recorded in 26% of this group of patients compared to 10.5% among patients with solitary OvC (P = 0.003). Patients with PPMBr had an exceptionally high prevalence of BRCA1-2 mutations (57%), irrespective of family history. CONCLUSIONS: Patients with PPMBr present with more advanced disease and invasive-type epithelial ovarian tumors when compared to cases associated with solitary OvC. The rate of BRCA1-2 mutations in Jewish women with OvC who had PPMBr is at least twice as high as in Jewish women with OvC as the solitary disease.

BRCA2 Protein↗
PubMed2000

Secondary resistance among 554 isolates of Helicobacter pylori after failure of therapy.

In a study to determine secondary resistance among Helicobacter pylori isolates, gastroenterologists from several German cities submitted over a 3-year period to centre A (Regensburg) or centre B (Freiburg) gastric biopsies from patients in whom one or more therapies to eradicate Helicobacter pylori had failed. Rates of resistance among the collections of 302 (centre A) and 252 (centre B) isolates were, respectively, as follows: to metronidazole, 75% and 66%; to clarithromycin, 58% and 49%; to amoxicillin, 0%; to ciprofloxacin, 9%; to doxycycline, 0%; and to rifampin, 0%. Resistance to clarithromycin was associated with metronidazole resistance in 89% and 85% of the isolates in centre A and centre B, respectively.

Amoxicillin↗
PubMed2000

Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction.

Insulin-dependent diabetes mellitus results when > 90% of the insulin-producing beta cells in the pancreatic islets are killed as a result of autoimmune attack by T cells. During the progression to diabetes, islet beta cells die as a result of different insults from the immune system. Agents such as perforin and granzymes, CD95 ligand and tumor necrosis factor-alpha, or cytokines and free-radicals have all been shown to cause beta cell apoptosis. The anti-apoptotic protein, Bcl-2, might protect against some of these stimuli. We have therefore generated transgenic mice expressing human Bcl-2 in their islet beta cells. Although Bcl-2 was able to prevent apoptosis induced by cytotoxic agents against beta cells in vitro, Bcl-2 alone could not prevent or ameliorate cytotoxic or autoimmune beta cell damage in vivo.

Age of Onset↗
PubMed2000

Mutations in the beginning of the rpoB gene can induce resistance to rifamycins in both Helicobacter pylori and Mycobacterium tuberculosis.

A clinical isolate of Helicobacter pylori that developed resistance to rifabutin during therapy carried an rpoB gene that retained a wild-type cluster region sequence but had acquired a novel codon 149 (V149F) mutation. In transformation experiments, the mutation was shown to confer high-level rifabutin resistance. The equivalent mutation (V176F) was present in several resistant isolates of Mycobacterium tuberculosis.

Amino Acid Sequence↗
PubMed2000

Mutations at four distinct regions of the rpoB gene can reduce the susceptibility of Helicobacter pylori to rifamycins.

The transformation of a panel of rpoB mutations (codons 525 to 586) from rifampin-resistant donor strains into Helicobacter pylori 2802A confirmed the MICs associated with the respective mutations. RpoB V149X random mutations were generated and induced different levels of resistance, depending on the replacement amino acid. Mutagenesis of the rpoB gene at codon position 701 (R701H) induced low-level resistance.

Anti-Bacterial Agents↗
PubMed2000

Novel marine-derived anticancer agents: a phase I clinical, pharmacological, and pharmacodynamic study of dolastatin 10 (NSC 376128) in patients with advanced solid tumors.

Dolastatin (DOLA)-10 is a pentapeptide isolated from the mollusc Dolabella auricularia with clinically promising antitumor activity documented in various in vitro and in vivo tumor models. The objectives of this Phase I study were to determine the maximum tolerated dose, evaluate toxic effects, and document any antitumor activity of this novel agent. Using an electrospray ionization mass spectroscopy system, we also characterized the clinical pharmacokinetics, pharmacodynamics, and metabolism of DOLA-10. The maximum tolerated dose was reached at 300 microg/m2. Granulocytopenia, the dose-limiting toxicity, was documented in 33% of the patients treated at that dose level. There were no episodes of thrombocytopenia or severe anemia (Hgb < 8), and no major nonhematological toxicity was observed. Stabilization of tumor growth was observed in four patients, but no objective responses were seen. Whereas a two-compartment model described the DOLA-10 plasma concentration-time data reasonably well, a three-compartment model consistently performed better. After a rapid distribution phase, DOLA-10 plasma levels declined with mean beta and gamma half-lives of 0.99 and 18.9 h, respectively. Significant interpatient and intrapatient variability in DOLA-10 plasma clearances was observed. The mean area under the concentration-time curve increased proportionally as the dose was escalated, but there was significant overlap between dose levels. The area under the concentration-time curve and the percentage of decline in neutrophils were correlated. A single DOLA-10 metabolite was detected in five patients. Unlike the in vitro studies of DOLA-10, the principal metabolite detected was an N-demethyl derivative, confirmed by mass spectroscopy. In all five subjects, the concentration of this metabolite never exceeded 2% of the simultaneously measured parent drug concentration. The available preclinical, pharmacological, and clinical data suggest that further study of escalated DOLA-10 dosing with cytokine support is warranted.

Adult↗