Biomedical subjects

H D Becker

Publications and source records attributed to H D Becker.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Usefulness of stress echocardiography for early diagnosis of anthracycline-induced cardiomyopathy].

BACKGROUND: Early evidence of drug induced cardiomyopathy is of great importance in oncological treatment, especially for application of Anthrazyklines. Stress echocar-diography (SE) has been proven to be of value in determining left ventricular function at rest and under stress. This study was performed to investigate the cardiac function under Anthrazykline-chemotherapy (aCT). PATIENTS AND METHODS: Patients with malignant thoracic tumors and indication for aCT underwent pharmacological SE (infusion of increasing dobutamin-doses, 5 microgram/kg/bw in 3 minute-steps) before starting aCT. Left ventricular ejection fraction (LVEF) and wall motion were measured. If the tumor decreased and the patients underwent 4 or more cycles of CT, at the end of the last CT another SE investigation was performed. RESULTS: 30 patients (20 men, 15 women; mean age 52, range 28 - 71) were included and the data were compared. Before aCT the mean LVEF was 59 % at rest and 71 % at maximum load, no disturbances of wall motion could be observed. After the end of aCT (mean dose 408 mg, range 256 - 549; mean 4.4 cycles, range 4 - 7) the LVEF was 58 at rest and 68 at maximum load (not significant) and there were also no disturbances of motion. CONCLUSION: SE is an alternative to echocardiography at rest in assessment of left ventricular function in patients receiving Anthrazykline-CT. With the doses applied no patient developed cardiomyopathy. So we consider SE a cost-effective method and safe for patients.

Adult↗

PubMed2001

Neostigmine increases postoperative colonic motility in patients undergoing colorectal surgery.

BACKGROUND: Gastrointestinal motility is frequently impaired after abdominal surgery. We investigated the effects of neostigmine on colonic motility in patients after colorectal surgery and in healthy volunteers. METHODS: Colonic motility was recorded by a manometry/barostat system in 12 patients after left colonic or rectal resection during baseline and after the intravenous administration of increasing doses of neostigmine on postoperative days 1, 2, and 3. In addition, colonic motility was recorded in 7 healthy volunteers. RESULTS: Neostigmine increased the colonic motility index. This increase was from 135 +/- 28 mm Hg/min at baseline to 574 +/- 219 mm Hg/min after administration of 5 microg/kg neostigmine on day 3 after surgery (mean +/- SEM, P <.05). In healthy volunteers, neostigmine at a dose of 5 microg/kg increased the colonic motility index from 184 +/- 73 to 446 +/- 114 mm Hg/min (P <.05). Barostat bag volumes decreased dose-dependently after neostigmine administration in patients as well as in volunteers, indicating an increase in colonic tone. CONCLUSIONS: Colonic motility and tone increased after neostigmine administration at a dose of 5 microg/kg in postoperative patients and in healthy volunteers. Neostigmine can be used to stimulate colonic motility after colorectal surgery and has a similar effect postoperatively as in healthy volunteers.

Adult↗

PubMed2001

Insulin-like growth factor I accelerates gastric ulcer healing by stimulating cell proliferation and by inhibiting gastric acid secretion.

BACKGROUND: Given the importance of Insulin-Like Growth Factor I (IGF-I) to intestinal maintenance and the presence of IGF-I in salivary glands, we hypothesized that IGF-I participates in the healing of gastric ulcers. The aim of the study was to determine: 1) whether IGF-I applied locally would support gastric ulcer healing by increasing cell proliferation and 2) the effect of IGF-I on gastric acid secretion. METHODS: Gastric ulcers were induced with a cryoprobe. Immediately thereafter, IGF-I (0.4, 4.0 and 40 microg) or vehicle was infiltrated perifocally. In another group, animals received a daily dose of 40 micromol omeprazole subcutaneously. Ulcer healing was evaluated by ulcer size and histological examination at 7 days. Pentagastrin-stimulated gastric acid secretion was evaluated in conscious rats with gastric fistula, after IGF-I (400 microg) had been injected intravenously. RESULTS: IGF-I significantly reduced ulcer size, but only at low doses (0.4 microg/kg body weight (BW), P = 0.008; 4 microg/kg BW, P = 0.001). This effect was similar to omeprazole treatment. Histological examination after IGF-I administration showed increased cell proliferation, increased IGF-I content and down-regulated IGF-I receptors. The secretory studies demonstrated a significant decrease in gastric acid secretion 30 min after IGF-I bolus injection (IGF-I: 53 +/- 11 microEq; vehicle: 116 +/- 5 microEq; P=0.001), which lasted for more than 1 h. CONCLUSION: IGF-I stimulates gastric ulcer healing, stimulating cell proliferation and inhibiting gastric acid secretion.

Animals↗

PubMed2001

Molecular genetic abnormalities in premalignant lung lesions: biological and clinical implications.

Lung cancer is a leading cause of cancer death worldwide; however, despite major advances in cancer treatment during the past two decades, the prognostic outcome of lung cancer patients has improved only minimally. This is largely due to the inadequacy of the traditional screening approach, which detects only well-established overt cancers and fails to identify precursor lesions in premalignant conditions of the bronchial tree. In recent years this situation has fundamentally changed with the identification of molecular abnormalities characteristic of premalignant changes; these concern tumour suppressor genes, loss of heterozygosity at crucial sites and activation of oncogenes. After considering the morphological modifications that occur in premalignant lesions of the bronchial tree, we analyse the alterations occurring in a series of relevant genes: p53 and its functional regulation by MDM2 and p14ARF, p16INK4, p15INK4b, FHIT, as well as LOH at important sites such as 3p, 8p, 9p and 5q. Activation of oncogenes is considered for K-ras, the cyclin D1, the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), and finally the c-myc oncogene. The expression of c-myc is influenced strongly by the presence of growth factors (GFs), among which EGF is of prime importance, as well as its receptor coded for by the c-erbB-2 oncogene. Basic knowledge at the molecular level has extremely important clinical implications with regard to early diagnosis, risk assessment and prevention, and therapeutic targets. The novel techniques for early diagnosis and screening of premalignant lung lesions, such as fluorescence bronchoscopy, endobronchial ultrasound, spiral computed tomography combined with precise spatial localization techniques, should basically change the approach to the problems raised by this disease and allow for an increased discovery rate of incipient lesions. Sequential applications will lead to the identification of individuals/populations at high risk, while the availability of accurate 'intermediate end points' will enable the effects of preventive trials to be monitored. Finally, the same molecular abnormalities may serve as 'starting points' for innovative treatments designed to restore the altered functions to normality. Recent developments in our knowledge and understanding of the molecular genetic abnormalities in premalignant lung lesions open an era of hope.

Gene Expression Regulation, Neoplastic↗

PubMed2001

In vitro test of new biomaterials for the development of a bioartificial pancreas.

The implantation of macroencapsulated islets has the potential to restore endogenous insulin secretion in type 1 diabetics, with no need for lifetime immunosuppression. To match the physiological fluctuations of blood glucose concentrations with appropriate insulin release, the macroencapsulation material must combine immunoprotection with optimal diffusion properties for glucose and insulin. The impact of chemical modifications of polysulphone (PSU) capillary polymers with a cutoff of 50 kD on glucose-induced insulin secretion of macroencapsulated rat islets was studied in perifusion experiments. The insulin release of free-floating islets showed the typical rapid response to glucose stimulation. Total insulin release (AUC between minute 30 and 120 of perifusion) reached 117+/-22 ng/ml. Blending PSU with polyvinylpyrrolidone or sodium-dodecyl-sulfate was not suitable for islet macroencapsulation, since glucose-induced insulin release was absent or disturbed. Hydroxy-methylation (CH2OH) of PSU improved the secretory behavior of macroencapsulated islets depending on the degree of PSU substitution (DS 0.8, AUC 62+/-15 ng/ml; DS 1.8, 111+/-24 ng/ml). In highly substituted PSU-capillaries the kinetics of glucose-induced insulin release was very similar to that observed in free-floating islets. Two consecutive glucose stimulations potentiated insulin release of free-floating islets during the second period of stimulation. Furthermore, freshly isolated macroencapsulated islets responded with more efficient insulin secretion after the initial priming. In conclusion, in vitro membrane screening identified highly substituted hydroxy-methylated PSU as the material of choice for islet encapsulation in a bioartificial pancreas.

Animals↗

PubMed2001

Endobronchial ultrasound (EBUS)--assessment of a new diagnostic tool in bronchoscopy for staging of lung cancer.

BACKGROUND AND OBJECTIVE: Conventional imaging procedures proved to be insufficient for staging of lung cancer, especially with respect to N-stage, infiltration of mediastinal structures, and early lung cancer. As also the view of the endoscopist is restricted, we developed the new method of endobronchial ultrasonography (EBUS) as an adjunct to conventional bronchoscopy. The initial technical problems were solved by development of a balloon catheter for application of miniaturized 20-MHz probes. PATIENTS AND METHODS: Between January and December, 1999 all patients with an indication for bronchoscopy and additional EBUS were documented prospectively. RESULTS: In 648 patients we used additional EBUS. Of these, 242 (37%) were female and 406 (63%) were male. The mean age was 49.2 (range 0-83) years. The mean procedure time for the bronchoscopies was 18.9 (range 5.7-38.9) min, and the mean time for EBUS was 6.3 (range 3.1-14.4) min. Side effects were comparatively rare. 34 patients (5%) needed supplementary oxygen during the examination, the others tolerated EBUS without any desaturation. CONCLUSION: EBUS is a new technology that can be easily applied and is well tolerated. It improves the results of bronchoscopy in addition to conventional diagnostic procedures. Further developments will be made in future to improve the application of ultrasound in chest medicine.

Adolescent↗

PubMed2001

Successful bronchoscopic placement of tracheobronchial stents without fluoroscopy.

BACKGROUND: Tracheobronchial stenting is performed increasingly often. Fluoroscopic control, which leads to significant radiation exposure for patients and staff, is recommended for the placement of metal stents. METHODS: All consecutive patients referred to two airway centers in need of airway stenting who received stents (Ultraflex; Boston Scientific, Natick, MA) underwent placement using endoscopic guidance only. All data were collected in an ongoing continuous database. RESULTS: One hundred stents were placed in 96 patients for central airway obstruction, and the data were reviewed. Stents were placed in all locations within the central airways for a variety of indications but mainly for malignant obstruction. No complications occurred, and all stents were placed satisfactorily. CONCLUSION: At centers with dedicated airway teams, Ultraflex stents can be quickly and safely inserted without the need for fluoroscopy. This saves radiation exposure to patients and to staff and may lead to a more cost-effective procedure.

Adult↗

PubMed2001

Long-term outcome and lung cancer incidence in patients with hemoptysis of unknown origin.

STUDY OBJECTIVE: To provide current data on the long-term outcome and incidence of lung cancer in a large cohort of patients with hemoptysis of unknown origin. DESIGN: A retrospective chart review followed by a telephone interview for follow-up. SETTING: A university-affiliated tertiary referral center for pulmonary diseases. PATIENTS: Seven hundred twenty-two patients who presented with hemoptysis from January 1990 to December 1993. One hundred thirty-five patients were identified as having hemoptysis of unknown origin. RESULTS: One hundred thirty-five patients (19%) had hemoptysis of unknown origin; follow-up data were obtained in 115 patients, of whom 100 were still alive. The mean time of observation was 6.6 years after initial presentation. Lung cancer developed in 7 of 115 patients (6%) and was unresectable once detected; all of these patients were smokers > 40 years old, and malignancy developed within 3 years after first presentation. CONCLUSIONS: Hemoptysis of unknown origin is present in a minority of patients presenting with hemoptysis if evaluated at a referral center for pulmonary diseases. Lung cancer seems to be increasing in these patients compared to previous studies, and closer follow-up or additional testing may be indicated in the defined population at risk.

Adult↗

PubMed2001

Genomics and the evolution of aminoacyl-tRNA synthesis.

Translation is the process by which ribosomes direct protein synthesis using the genetic information contained in messenger RNA (mRNA). Transfer RNAs (tRNAs) are charged with an amino acid and brought to the ribosome, where they are paired with the corresponding trinucleotide codon in mRNA. The amino acid is attached to the nascent polypeptide and the ribosome moves on to the next codon. Thus, the sequential pairing of codons in mRNA with tRNA anticodons determines the order of amino acids in a protein. It is therefore imperative for accurate translation that tRNAs are only coupled to amino acids corresponding to the RNA anticodon. This is mostly, but not exclusively, achieved by the direct attachment of the appropriate amino acid to the 3'-end of the corresponding tRNA by the aminoacyl-tRNA synthetases. To ensure the accurate translation of genetic information, the aminoacyl-tRNA synthetases must display an extremely high level of substrate specificity. Despite this highly conserved function, recent studies arising from the analysis of whole genomes have shown a significant degree of evolutionary diversity in aminoacyl-tRNA synthesis. For example, non-canonical routes have been identified for the synthesis of Asn-tRNA, Cys-tRNA, Gln-tRNA and Lys-tRNA. Characterization of non-canonical aminoacyl-tRNA synthesis has revealed an unexpected level of evolutionary divergence and has also provided new insights into the possible precursors of contemporary aminoacyl-tRNA synthetases.

Amino Acyl-tRNA Synthetases↗

PubMed2001

[Dissection technique--is ultrasound the best method?].

Preventive hemostasis is extremely important in endoscopic surgery. Ultrasonic dissectors are used very often. We tested the occlusion safety of bipolar forceps and ultrasonic dissector for porcine vessels. Thermographic videos showed maximum temperature up to 200 degrees C when using one ultrasonic dissector. The lateral damage zone in vivo and in vitro measured between 2 and 6 mm.

Animals↗

PubMed2001

[Gene therapy in diabetic foot].

In gene therapy nucleic acids are used for therapy. There are three different concepts in gene therapy for chronic wounds. (1) Synthesis of human recombinant growth factors by gene therapy techniques, (2) Ex-vivo transfection of cell cultures (fibroblasts, keratinocytes) with growth factor DNA and subsequent transplantation of transfected cells on chronic wounds. (3) In-vivo transfection with growth factor DNA, e.g., gene gun, liposomes, viral vector. Clinical studies on gene therapy for diabetic foot ulcers are only available for the local application of human recombinant PDGF-BB growth factor. Meta-analysis shows there is a low but significant effect of PDGF-BB on neuropathic diabetic ulcers, leading to an increase of healing by 10-15% within 20 weeks of treatment.

Animals↗

PubMed2000

Context-dependent anticodon recognition by class I lysyl-tRNA synthetases.

Lysyl-tRNA synthesis is catalyzed by two unrelated families of aminoacyl-tRNA synthetases. In most bacteria and all eukarya, the known lysyl-tRNA synthetases (LysRSs) are subclass IIb-type aminoacyl-tRNA synthetases, whereas many archaea and a scattering of bacteria contain an unrelated class I-type LysRS. Examination of the recognition of partially modified tRNA(Lys) anticodon variants by a bacterial (from Borrelia burgdorferi) and an archaeal (from Methanococcus maripaludis) class I lysyl-tRNA synthetase revealed differences in the pattern of anticodon recognition between the two enzymes. U35 and U36 were both important for recognition by the B. burgdorferi enzyme, whereas only U36 played a role in recognition by M. maripaludis LysRS. Examination of the phylogenetic distribution of class I LysRSs suggested a correlation between recognition of U35 and U36 and the presence of asparaginyl-tRNA synthetase (AsnRS), which also recognizes U35 and U36 in the anticodon of tRNA(Asn). However, the class II LysRS of Helicobacter pylori, an organism that lacks AsnRS, also recognizes both U35 and U36, indicating that the presence of AsnRS has solely influenced the phylogenetic distribution of class I LysRSs. These data suggest that competition between unrelated aminoacyl-tRNA synthetases for overlapping anticodon sequences is a determinant of the phylogenetic distribution of extant synthetase families. Such patterns of competition also provide a basis for the two separate horizontal gene transfer events hypothesized in the evolution of the class I lysyl-tRNA synthetases.

Anticodon↗

PubMed2000

Domain-specific recruitment of amide amino acids for protein synthesis.

The formation of aminoacyl-transfer RNA is a crucial step in ensuring the accuracy of protein synthesis. Despite the central importance of this process in all living organisms, it remains unknown how archaea and some bacteria synthesize Asn-tRNA and Gln-tRNA. These amide aminoacyl-tRNAs can be formed by the direct acylation of tRNA, catalysed by asparaginyl-tRNA synthetase and glutaminyl-tRNA synthetase, respectively. A separate, indirect pathway involves the formation of mis-acylated Asp-tRNA(Asn) or Glu-tRNA(Gln), and the subsequent amidation of these amino acids while they are bound to tRNA, which is catalysed by amidotransferases. Here we show that all archaea possess an archaea-specific heterodimeric amidotransferase (encoded by gatD and gatE) for Gln-tRNA formation. However, Asn-tRNA synthesis in archaea is divergent: some archaea use asparaginyl-tRNA synthetase, whereas others use a heterotrimeric amidotransferase (encoded by the gatA, gatB and gatC genes). Because bacteria primarily use transamidation, and the eukaryal cytoplasm uses glutaminyl-tRNA synthetase, it appears that the three domains use different mechanisms for Gln-tRNA synthesis; as such, this is the only known step in protein synthesis where all three domains have diverged. Closer inspection of the two amidotransferases reveals that each of them recruited a metabolic enzyme to aid its function; this provides direct evidence for a relationship between amino-acid metabolism and protein biosynthesis.

Amides↗

PubMed2000

The heterotrimeric Thermus thermophilus Asp-tRNA(Asn) amidotransferase can also generate Gln-tRNA(Gln).

Thermus thermophilus strain HB8 is known to have a heterodimeric aspartyl-tRNA(Asn) amidotransferase (Asp-AdT) capable of forming Asn-tRNA(Asn) [Becker, H.D. and Kern, D. (1998) Proc. Natl. Acad. Sci. USA 95, 12832-12837]. Here we show that, like other bacteria, T. thermophilus possesses the canonical set of amidotransferase (AdT) genes (gatA, gatB and gatC). We cloned and sequenced these genes, and constructed an artificial operon for overexpression in Escherichia coli of the thermophilic holoenzyme. The overproduced T. thermophilus AdT can generate Gln-tRNA(Gln) as well as Asn-tRNA(Asn). Thus, the T. thermophilus tRNA-dependent AdT is a dual-specific Asp/Glu-AdT resembling other bacterial AdTs. In addition, we observed that removal of the 44 carboxy-terminal amino acids of the GatA subunit only inhibits the Asp-AdT activity, leaving the Glu-AdT activity of the mutant AdT unaltered; this shows that Asp-AdT and Glu-AdT activities can be mechanistically separated.

Amino Acid Sequence↗

PubMed2000

[Inguinal hernia: accident sequela?].

The evaluation of an inguinal hernia as a result of an accident has to be newly discussed because of new radiologic tools like US, CT and MRI. Therefore an injury of the abdominal wall after an adequate trauma has to be proved. This can also be achieved by radiology, in which signs of injury, as contusion and hematoma, can be detected. Moreover the histological signs of injury and bleeding, i.e. fibrinexudation, capillary granulation tissue, round cells, siderophages, fibrocytes and fibroblast proliferation must be proved.

Abdominal Injuries↗

PubMed2000

Thermus thermophilus contains an eubacterial and an archaebacterial aspartyl-tRNA synthetase.

Thermus thermophilus possesses two aspartyl-tRNA synthetases (AspRSs), AspRS1 and AspRS2, encoded by distinct genes. Alignment of the protein sequences with AspRSs of other origins reveals that AspRS1 possesses the structural features of eubacterial AspRSs, whereas AspRS2 is structurally related to the archaebacterial AspRSs. The structural dissimilarity between the two thermophilic AspRSs is correlated with functional divergences. AspRS1 aspartylates tRNA(Asp) whereas AspRS2 aspartylates tRNA(Asp), and tRNA(Asn) with similar efficiencies. Since Asp bound on tRNA(Asn) is converted into Asn by a tRNA-dependent aspartate amidotransferase, AspRS2 is involved in Asn-tRNA(Asn) formation. These properties relate functionally AspRS2 to archaebacterial AspRSs. The structural basis of the dual specificity of T. thermophilus tRNA(Asn) was investigated by comparing its sequence with those of tRNA(Asp) and tRNA(Asn) of strict specificity. It is shown that the thermophilic tRNA(Asn) contains the elements defining asparagine identity in Escherichia coli, part of which being also the major elements of aspartate identity, whereas minor elements of this identity are missing. The structural context that permits expression of aspartate and asparagine identities by tRNA(Asn) and how AspRS2 accommodates tRNA(Asp) and tRNA(Asn) will be discussed. This work establishes a distinct structure-function relationship of eubacterial and archaebacterial AspRSs. The structural and functional properties of the two thermophilic AspRSs will be discussed in the context of the modern and primitive pathways of tRNA aspartylation and asparaginylation and related to the phylogenetic connexion of T. thermophilus to eubacteria and archaebacteria.

Acylation↗

PubMed2000

One polypeptide with two aminoacyl-tRNA synthetase activities.

The genome sequences of certain archaea do not contain recognizable cysteinyl-transfer RNA (tRNA) synthetases, which are essential for messenger RNA-encoded protein synthesis. However, a single cysteinyl-tRNA synthetase activity was detected and purified from one such organism, Methanococcus jannaschii. The amino-terminal sequence of this protein corresponded to the predicted sequence of prolyl-tRNA synthetase. Biochemical and genetic analyses indicated that this archaeal form of prolyl-tRNA synthetase can synthesize both cysteinyl-tRNA(Cys) and prolyl-tRNA(Pro). The ability of one enzyme to provide two aminoacyl-tRNAs for protein synthesis raises questions about concepts of substrate specificity in protein synthesis and may provide insights into the evolutionary origins of this process.

Amino Acyl-tRNA Synthetases↗

PubMed2000

Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach.

Specific immunotherapy of cancer utilizes tumor-directed cytotoxic T lymphocytes (CTL) that lyse tumor cells presenting MHC class I-associated peptides derived from tumor-associated proteins. Many tumor-associated gene products are known, but corresponding T cell epitopes are only known for relatively few of these. The most commonly used approaches to identify such antigens require pre-existing CTL lines or clones. By using a CTL-independent high performance liquid chromatography mass spectrometry (HPLC MS)-based approach we identified HLA-A2-presented peptides from carcinoembryonic antigen and wild-type p53 with a copy number as low as eight molecules per cell. Potential epitopes were predicted from the sequences of known tumor antigens and the corresponding synthetic peptides were analyzed by nanocapillary HPLC MS. In parallel, peptides were extracted from fresh, solid tumor tissue or tumor cell lines and analyzed in the same way. Upon co-elution of a natural peptide with a predicted peptide of the same mass, the peptide sequence was confirmed by on-line tandem MS. This approach allows rapid screening of large numbers of tumor-associated gene products for naturally processed peptides presented by different MHC class I molecules as a prerequisite for efficient epitope identification and rapid transfer to therapeutic vaccine trials.

Antigens, Neoplasm↗