Search PubMed⌕ Search

Biomedical subjects

E Berger

Publications and source records attributed to E Berger.

At least 19 recordsLinked to original sources
PubMed2003

Early optical emission from the gamma-ray burst of 4 October 2002.

Observations of the long-lived emission--or 'afterglow'--of long-duration gamma-ray bursts place them at cosmological distances, but the origin of these energetic explosions remains a mystery. Observations of optical emission contemporaneous with the burst of gamma-rays should provide insight into the details of the explosion, as well as into the structure of the surrounding environment. One bright optical flash was detected during a burst, but other efforts have produced negative results. Here we report the discovery of the optical counterpart of GRB021004 only 193 seconds after the event. The initial decline is unexpectedly slow and requires varying energy content in the gamma-ray burst blastwave over the course of the first hour. Further analysis of the X-ray and optical afterglow suggests additional energy variations over the first few days.

Journal Article↗
PubMed2003

Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients.

BACKGROUND: Patients with relapsing or refractory multiple myeloma have poor prognosis. Few compounds are active in these patients and response duration remains short. We report the results of an open phase II trial evaluating the efficacy and safety of fotemustine monotherapy. PATIENTS AND METHODS: Twenty-one patients with relapsing (17) or refractory (four) multiple myeloma received fotemustine 100 mg/m(2) on an outpatient basis on days 1 and 8 of the induction cycle, followed after a 6-week rest period by fotemustine 100 mg/m(2) every 3 weeks until progression or unacceptable toxicity. Fotemustine pharmacokinetics during the first day of induction was compared between patients with normal or abnormal renal function. RESULTS: Five of 20 eligible patients had an objective response giving an intention-to-treat response rate of 25% [95% confidence interval (CI) 6% to 44%] and a 35.7% response rate (95% CI 11% to 61%) in the 14 patients having received at least four injections of fotemustine. The median time to objective response was 8.9 months. The median times to progression and survival were 13.8 and 23.1 months, respectively, with a 2-year survival rate of 49%. The main toxicity was myelosuppression with grade 3-4 neutropenia and thrombocytopenia in 66% and 71% of patients, respectively. There was one toxic death by sepsis after induction. The pharmacokinetic parameters in renal-impaired patients were not significantly different from those in patients with normal renal function with a similar incidence of grade 3-4 toxicity in both groups. CONCLUSIONS: Fotemustine as a single agent has definite activity in patients with relapsing or refractory multiple myeloma, with acceptable toxicity and can be administered at conventional doses in patients with mild or moderate renal impairment.

Aged↗
PubMed2002

Screening for peptide affinity ligands on CIM monoliths.

Screening of peptide ligands for affinity chromatography usually involves incubation with the target protein in a batch system. In an additional step, peptides with fast binding kinetics have to be selected in respect to satisfactory performance under flow conditions on a support ensuring optimal three-dimensional presentation of the peptide. We have developed a rapid screening system based on peptide synthesis and screening on CIM((R)) disks. The disk size was minimized to fit into microplates usually applied for solid-phase extraction. In combination with a vacuum manifold, semi-automated peptide synthesis and screening for binding to a target protein under simulated chromatography conditions are possible. Various analytical methods can be applied for parallel and automated determination of the quantity, integrity, or activity of the target protein in the flow through or bound to the affinity support. This system also allows parallel screening for suitable chromatographic conditions like running buffer, washing, and elution conditions.

Carrier Proteins↗
PubMed2002

[Systematic development of a scale for determination of health-related quality of life in multiple trauma patients. The Polytrauma Outcome (POLO) Chart].

Even years after having sustained multiple injuries patients often suffer from its sequelae. These comprise restrictions in physical function, but also pain, social and psychological impairments. Although the Meran Consensus Conference in 1990 defined the contents of "quality of life" (QoL) measures in surgery, still no instrument is available for the valid assessment of all relevant QoL domains in multiple injured patients. This paper describes the systematic development of a modular instrument for the assessment of health related QoL. Within three phases (phase I: generation of items, phase II: item reduction, phase III: pre-testing in 70 multiple injured and control patients) a questionnaire of 57 items was developed, which measures all relevant trauma-related aspects of QoL after acute hospital care. In combination with the Glascow Outcome Scale (GOS), the EUROQOL and the SF-36, the newly developed instrument builds the Polytrauma Outcome Chart (POLO-Chart) which will also be used as "Part E" for outcome assessment within the "Trauma registry" of the German Society for Trauma Surgery. In phase IV, the POLO-Chart will finally be validated in five trauma centres (Celle, Essen, Hanover, Cologne und Munich).

Activities of Daily Living↗
PubMed2002

Mutational analysis of a blood coagulation factor VIII-binding peptide.

A peptide screened from a combinatorial peptide library with the sequence EYKSWEYC performed best as a ligand for affinity chromatography of human blood coagulation factor VIII (FVIII). With this peptide immobilized on monolithic CIM columns via epoxy groups we were able to capture FVIII from diluted plasma. Rational substitution of amino acids by spot synthesis revealed that lysine and cysteine can be exchanged for almost all other proteinogenic amino acids without loss of affinity to FVIII. This offers the possibility of site-specific attachment via either one of these residues or the N- or C-terminus. The aliphatic positions O5 (tryptophan) and O7 (tyrosine), together with the charged position O6 (glutamic acid), seem to form the core of the binding unit. In the positions with aliphatic amino acids, substitution by tyrosine or phenylalanine, and in the positions with charged amino acids, substitution by aspartic acid or lysine, preserved the affinity to FVIII. The functionality of the selected peptides was confirmed by affinity chromatography. Selective binding and elution could be achieved.

Amino Acid Sequence↗
PubMed2001

Determination of the quadratic slope parameter in eta-->3pi(0) decay.

We have determined the quadratic slope parameter alpha for eta-->3pi(0) to be alpha = -0.031(4) from a 99% pure sample of 10(6)eta-->3pi(0) decays produced in the reaction pi(-)p-->n(eta) close to the eta threshold using the Crystal Ball detector at the AGS. The result is four times more precise than the present world data and disagrees with current chiral perturbation theory calculations by about four standard deviations.

Journal Article↗
PubMed2001

Acid-base catalysis by UDP-galactose 4-epimerase: correlations of kinetically measured acid dissociation constants with thermodynamic values for tyrosine 149.

The steady-state kinetic parameters for epimerization of UDP-galactose by UDP-galactose 4-epimerase from Escherichia coli (GalE), Y149F-GalE, and S124A-GalE have been measured as a function of pH. The deuterium kinetic isotope effects for epimerization of UDP-galactose-C-d(7) by these enzymes have also been measured. The results show that the activity of wild-type GalE is pH-independent in the pH range of 5.5-9.3, and there is no significant deuterium kinetic isotope effect in the reaction of UDP-galactose-C-d(7). It is concluded that the rate-limiting step for epimerization by wild-type GalE is not hydride transfer and must be either a diffusional process or a conformational change. Epimerization of UDP-galactose-C-d(7) by Y149F-GalE proceeds with a pH-dependent deuterium kinetic isotope effect on k(cat) of 2.2 +/- 0.4 at pH 6.2 and 1.1 +/- 0.5 at pH 8.3. Moreover, the plot of log k(cat)/K(m) breaks downward on the acid side with a fitted value of 7.1 for the pK(a). It is concluded that the break in the pH-rate profile arises from a change in the rate-limiting step from hydride transfer at low pH to a conformational change at high pH. Epimerization of UDP-galactose-C-d(7) by S124A-GalE proceeds with a pH-independent deuterium kinetic isotope effect on k(cat) of 2.0 +/- 0.2 between pH 6 and 9. Both plots of log k(cat) and log k(cat)/K(m) display pH dependence. The plot of log k(cat) versus pH breaks downward with a pK(a) of 6.35 +/- 0.10. The plot of log k(cat)/K(m) versus pH is bell-shaped, with fitted pK(a) values of 6.76 +/- 0.09 and 9.32 +/- 0.21. It is concluded that hydride transfer is rate-limiting, and the pK(a) of 6.7 for free S124A-GalE is assigned to Tyr 149, which displays the same value of pK(a) when measured spectrophotometrically in this variant. Acid-base catalysis by Y149F-GalE is attributed to Ser 124, which is postulated to rescue catalysis of proton transfer in the absence of Tyr 149. The kinetic pK(a) of 7.1 for free Y149F-GalE is lower than that expected for Ser 124, as proven by the pH-dependent kinetic isotope effect. Epimerization by the doubly mutated Y149F/S124A-GalE proceeds at a k(cat) that is lower by a factor of 10(7) than that of wild-type GalE. This low rate is attributed to the synergistic actions of Tyr 149 and Ser 124 in wild-type GalE and to the absence of any internal catalysis of hydride transfer in the doubly mutated enzyme.

Alanine↗
PubMed2001

Discovery of radio emission from the brown dwarf LP944-20.

Brown dwarfs are not massive enough to sustain thermonuclear fusion of hydrogen at their centres, but are distinguished from gas-giant planets by their ability to burn deuterium. Brown dwarfs older than approximately 10 Myr are expected to possess short-lived magnetic fields and to emit radio and X-rays only very weakly from their coronae. An X-ray flare was recently detected on the brown dwarf LP944-20, whereas previous searches for optical activity (and one X-ray search) yielded negative results. Here we report the discovery of quiescent and flaring radio emission from LP944-20, with luminosities several orders of magnitude larger than predicted by the empirical relation between the X-ray and radio luminosities that has been found for many types of stars. Interpreting the radio data within the context of synchrotron emission, we show that LP944-20 has an unusually weak magnetic field in comparison to active M-dwarf stars, which might explain the previous null optical and X-ray results, as well as the strength of the radio emissions compared to those at X-ray wavelengths.

Journal Article↗
PubMed2001

RNA editing at the Q/R site for the glutamate receptor subunits GLUR2, GLUR5, and GLUR6 in hippocampus and temporal cortex from epileptic patients.

Posttranscriptional editing of mRNA is a phenomenon that generates molecular heterogeneity and functional variety. With the intention to test if RNA editing plays a role in pathological processes, which contribute to seizure maintenance, we examined the ratio of the unedited (Q) to edited (R) form of the AMPA receptor subunit GluR2 and kainate receptor subunits GluR5 and GluR6 in the hippocampus and temporal cerebral cortex, both excised from patients with pharmacoresistant temporal lobe epilepsies. We compared the data with samples from nonepileptic human control tissue (autopsy tissue). The ratio of Q/R editing was analyzed by means of reverse transcription-polymerase chain reaction followed by a restriction enzyme assay. We found that the editing efficiency for the kainate receptor subunits GluR5 and GluR6 was significantly higher in temporal cortex than in normal controls. The alteration in GluR5 and GluR6 mRNA editing in the neocortical tissue may reflect an adaptive reaction of ongoing seizure activity to prevent excessive Ca(2+) influx.

Adolescent↗
PubMed2001

Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase activity.

The aims of this phase I study in patients with recurrent malignant gliomas were to determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine when combined with a fixed dose of procarbazine (PCZ), and to evaluate the extent of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating lymphocytes during treatment. Sixteen patients received an induction cycle consisting of 100 mg/day oral PCZ for 12 consecutive days and a 1-h intravenous infusion of fotemustine given 4 h after PCZ on days 5 and 12 at escalated doses (50, 75, 100 and 125 mg/m2/day). After a 6-week rest period, a maximum of 4 maintenance cycles (PCZ 300 mg/day, 4 days; fotemustine, day 4) was given every 4 weeks. ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake. Fifteen patients had previously received at least one nitrosourea-based chemotherapy, associated with PCZ in 12 cases. The MTD of fotemustine was 125 mg/m2 (days 5 and 12) with myelosuppression as the dose limiting toxicity (DLT). At this dose level, half of patients experienced grade 3 anemia, neutropenia or thrombopenia. No extra-hematological DLT was observed. No significant depletion of ATase activity by PCZ was evidenced. One partial response and 7 stable diseases were obtained leading to a disease control rate of 50%. The median times to progression and survival were 2.6 and 9.7 months, respectively. This combined regimen of PCZ and fotemustine was well tolerated with a good disease control rate in heavily pretreated glioma patients and merits further investigation in phase II studies.

Adult↗
PubMed2001

Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathway.

Melatonin-sensitive receptors were expressed in Xenopus laevis oocytes following an injection of mRNA from rat brain. The administration of 0.1-100 micromol/L melatonin to voltage-clamped oocytes activates calcium-dependent chloride currents via a pertussis toxin-sensitive G protein and the phosphoinositol pathway. To determine which melatonin receptor type (mt1, MT2, MT3) is functionally expressed in the Xenopus oocytes, we used (i) agonists and antagonists of different receptor types to characterize the pharmacological profile of the expressed receptors and (ii) a strategy of inhibiting melatonin receptor function by antisense oligonucleotides. During pharmacological screening administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5-methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N-acetyltryptamine (GR135,531) exerted no detectable membrane currents. The melatonin response was abolished by a preceding administration of the antagonists 2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT). In the antisense experiments, in the control group the melatonin response occurred in 45 of 54 mRNA-injected oocytes (83%). Co-injection of the antisense oligonucleotide, corresponding to the mt1 receptor mRNA, caused a marked and significant reduction in the expression level (13%; P < 0.001). In conclusion, the results demonstrate that injection of mRNA from rat brain in Xenopus oocytes induced the expression of the mt1 receptor which is coupled to the phosphoinositol pathway.

Animals↗
PubMed2001

How much reduction in portal pressure is necessary to prevent variceal rebleeding? A longitudinal study in 225 patients with transjugular intrahepatic portosystemic shunts.

OBJECTIVES: This longitudinal study determines the risk of rebleeding in relation to the reduction of the portosystemic pressure gradient in patients with a transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding. METHODS: The study included 225 patients in whom a TIPS revision was indicated by the endoscopic finding of varices with a high risk for rebleeding (n = 167) or a recent variceal rebleed (n = 58). The portosystemic pressure gradient was determined before and after TIPS placement and at revision performed after a mean of 10 +/- 15 months. RESULTS: The portosystemic pressure gradient at revision approached the index pressure gradient before TIPS implantation (23.1 +/- 5.5 mm Hg) by 8.4 +/- 31%. Rebleeding was inversely correlated with the reduction in index pressure gradient found at revision. Thus, 80% of rebleedings occurred with pressure gradients close to the index pressure gradient (< 25% reduction) or with gradients equal to or greater than the index pressure gradient. In contrast, only one patient (0.4%) and three patients (1.3%) rebled with a pressure gradient of < 12 mm Hg or a reduction of the index pressure gradient by > 50%, respectively. Kaplan-Meier analysis of rebleeding, which included the 225 patients at risk, showed a probability of rebleeding of 18%, 7%, and 1% for a reduction of the index pressure gradient by 0%, 25-50%, and > 50%, respectively. CONCLUSIONS: Most rebleedings occurred with pressure gradients similar to the index-pressure gradient measured at first bleeding. Accordingly, a graded reduction by 25-50% sufficiently prevents rebleeding. It can be assumed that, in comparison with the widely used threshold value of 12 mm Hg, a reduction by 25-50% may have a favorable benefit-to-risk ratio with respect to shunt-induced hepatic encephalopathy and liver failure. It should therefore be a goal in the decompressive treatment of portal hypertension and maintained during follow-up of patients with variceal bleeding.

Adult↗
PubMed2001

A novel form of platelet-type 12-lipoxygenase mRNA in human vascular smooth muscle cells.

The lipoxygenase pathway has been implicated in the growth, migration, and contraction of vascular smooth muscle cells (VSMCs). However, the precise type of lipoxygenase present in the vascular wall has not been characterized. In this study, we used a specific reverse-transcriptase polymerase chain reaction method with 2 sets of specific primers on total RNA and polyA (+)RNA of normal human VSMCs prepared from umbilical artery. Two forms of platelet-type 12-lipoxygenase mRNA were present in human VSMCs: the already published form cloned from human erythroleukemia cells and a variant form of platelet-type 12-lipoxygenase, which includes 2 additional sequences consistent with the 2 introns (D and E). This novel form of 12-lipoxygenase poly A (+)RNA was downregulated by lipopolysaccharide (10 ug/ml) and upregulated by epidermal growth factor (100 ng/ml) but was not affected by angiotensin II (10(-7) mol/l). We developed a rabbit anti-human platelet-type 12-lipoxygenase polyclonal antibody directed against a 24-amino acid peptide encoded within exon 4. Western immunoblotting of protein extracted from VSMCs and umbilical artery and platelet extract with this antibody showed a coordinate 110-kDa protein and the already-described 70-kDa band detected in platelets and cord homogenate. Another 120-kDa protein was consistently detected in cord extracts but not in platelet or VSMC homogenates. The immunohistochemistry study performed with the same antibody showed extensive cytoplasmic staining of VSMCs. The specific role of these different forms of platelet-type 12-lipoxygenase is subject to further investigation.

Alternative Splicing↗
PubMed2001

Vigilance scoring in children with acquired brain injury: Vienna Vigilance Score in comparison with usual coma scales.

An instrument in neurologic rehabilitation for the assessment of a person's clarity of consciousness must fulfill the need to provide the rehabilitation team with some information regarding the structuring of the rehabilitation process. The Vienna Vigilance Score is oriented toward cooperation within the rehabilitation team with the specific advantage of focus on the subject status of the patient on the basis of the dialogue. It does not use painful stimuli and is oriented toward the next developmental step of the rehabilitation process. The first extensive application of the Vienna Vigilance Score was carried out in a 3-year study of 38 children and adolescents. We report the comparison with other coma scales (Glasgow Coma Scale, Children's Coma Score, and Modified Glasgow Coma Scale) on 24 children and adolescents (1.4-16.8 years of age). The results showed satisfying statistical parameters: measuring range comparable with other scales; a Kendall tau correlation of .59 on both the Modified Glasgow Coma Scale and the Children's Coma Scale and of .66 on the Glasgow Coma Scale; a Spearman's rank order correlation of .70 to both the Modified Glasgow Coma Scale and the Children's Coma Scale and of .78 on the Glasgow Coma Scale. By accepting the Glasgow Coma Scale as a gold standard for classification of the level of coma, we can confirm satisfactory measuring qualities for the Vienna Vigilance Score.

Adolescent↗
PubMed2001

The hormonal milieu in early stages of bone cell differentiation modifies the subsequent sex-specific responsiveness of the developing bone to gonadal steroids.

We have established previously that rat bone tissue, as well as rat and human-derived bone cells in culture, show a sex-specific response to gonadal steroids in stimulation of the specific activity of the BB isozyme of creatine kinase (CK) and DNA synthesis. This response could be modified by manipulation of the endocrine environment during early stages in rat development. To further examine the influence of changing hormonal steroid milieu and vitamin D status on the action of gonadal steroids in developing bone tissue, we used two models of ectopic bone formation: demineralized tooth matrix (DTM) implanted under the skin, and femoral bone marrow (BM) transplanted under the kidney capsule of a syngeneic recipient mouse. The response to gonadal steroids in ossicles developed from implanted DTM depended on the recipient's gender; injection of estradiol 17beta (E2; 5 microg) into young female mice 21 days after DTM implantation increased, 24 h later, CK activity in the newly formed ossicles by approximately 60%, whereas injection of dihydrotestosterone (DHT; 50 microg) had no effect on CK activity. In contrast, in male mice, DHT but not E2 increased CK activity in the ossicles by approximately 50%. This sex-specific response was abolished in gonadectomized mice resulting in a similar response of the ossicles to both E2 and DHT. When DTM was implanted into vitamin D- deficient female mice, there was a lower basal CK activity and a significantly diminished response to E2 in the newly formed bone tissues. When BM, which contains mesenchymal and stromal cells and committed osteoprogenitor cells, was transplanted into 6-week-old intact or gonadectomized female or male mice, the response of the newly formed bone ossicles, 21 days after transplantation, to E2 or to DHT was according to the gender of the donor. Bone formed from BM obtained from female mice responded to E2 only and those formed from male BM responded to DHT only. Ossicles developed from BM obtained from gonadectomized mice showed lack of response to either gonadal steroid. Furthermore, only approximately 25% of the BM transplants obtained from castrated (CAST) male donors developed into ossicles. Ossicles formed from BM obtained from vitamin D-deficient female donors showed lack of response to gonadal steroids. These findings suggest that the manipulation of the hormonal milieu in early stages of the differentiation sequence of bone cells modifies the subsequent selective responsiveness of the developing bone tissue to gonadal steroids.

24,25-Dihydroxyvitamin D 3↗
PubMed2001

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

Adult↗
PubMed2001

[Protective effect of appendectomy on the development of ulcerative colitis. A case-control study].

AIMS: To examine by a case-control study the relationship between appendectomy and subsequent ulcerative colitis development in a French population. METHODS: A total of 150 patients with ulcerative colitis were matched for age (+/- 5 years) and sex, with 150 controls recruited in a preventive medicine center. The following data were collected from medical records and by standardised questionnaire in consultation or by phone: appendectomy and tonsillectomy before the onset of ulcerative colitis, smoking habits and area of residence. RESULTS: The rate of previous appendectomy in patients with ulcerative colitis was 8% (12/150) compared with 30.6% (46/150) in the control group (P=0.001). There was no significant association between ulcerative colitis and tonsillectomy (25.3 and 27.3% in the control and the ulcerative colitis groups, respectively). Smoking was more frequent in the control group (36%) than in the ulcerative colitis group (25.3%) but the difference was not significant (P=0.07). In multivariate analysis, the risk of developing ulcerative colitis was significantly lower after previous appendectomy (odds ratio=0.26; 95% confidence interval: 0.13-0.55; P=7 x 10(-4)). CONCLUSION: Our study confirms the inverse association between appendectomy and subsequent ulcerative colitis, in a French population, after adjusting on smoking.

Adult↗