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T Weber

Publications and source records attributed to T Weber.

At least 73 records · Page 4Linked to original sources
PubMed2001

Exploring the domain structure of modular nonribosomal peptide synthetases.

Recently, considerable insight has been gained into the modular organization of nonribosomal peptide synthetases (NRPS). The three-dimensional structures of domains associated with substrate adenylation and covalent binding have been solved as well as the structure of a priming enzyme required for the post-translational modification of NRPS. Taken together, these studies will help us to understand the architecture of these mega-enzymes.

Models, Molecular↗
PubMed2001

Abrupt rise of the longitudinal recoil ion momentum distribution for ionizing collisions.

We report on the experimental observation of an abrupt rise in the longitudinal momentum distribution of recoil ions created in proton helium collision. The details of this structure can be related to electrons traveling with the velocity of the projectile [electron capture to the continuum (ECC)]. The longitudinal as well as the transverse distribution of the recoil ions can be explained as a continuation of the momentum distribution from ions resulting from electron capture illustrating the smooth transition from the capture to bound states of the projectile to the ECC.

Journal Article↗
PubMed2001

Selective cancer cell killing by alpha-tocopheryl succinate.

We report that alpha-tocopheryl succinate, a vitamin E analogue with pro-apoptotic properties, selectively kills cells with a malignant or transformed phenotype, i.e. multiple haematopoietic and carcinoma cell lines, while being non-toxic to normal, i.e. primary and non-transformed cells. These findings strongly suggest a potential of this micronutrient in the therapy and/or prevention of cancer without significant side-effects.

Apoptosis↗
PubMed2001

Minimal residual disease in thyroid carcinoma.

The detection of disseminated tumor cells in differentiated (DTC) and medullary thyroid carcinomas (MTC) is one of the main topics in current thyroid cancer research. Immunocytochemistry and polymerase chain reaction (PCR) provide the tools for the identification of a small number of thyroid cancer cells in peripheral blood and cervical lymph nodes. Thyroid-specific markers, such as thyroglobulin (Tg) mRNA and thyroid peroxidase (TPO) mRNA, have been detected with RT-PCR in blood samples of tumor patients and healthy control subjects. To prevent false-positive results, quantitative PCR systems were established. Tumor-specific markers, such as telomerase activity and cytokeratin 20 (CK20), have been detected in various epithelial tumors. Amplification products of these markers were found in blood samples and in fine-needle aspiration (FNA) biopsies of patients with thyroid carcinomas. Using molecular detection of disseminated tumor cells in cervical lymph nodes with CK20 RT-PCR, a higher percentage of involved lymph nodes was detected compared to immunohistochemistry. The results of the presented studies may help researchers to develop more sensitive methods for early tumor cell dissemination, and refine risk groups that might benefit from more extensive surgical procedures or adjuvant therapy. However, the prognostic value of minimal residual disease (MRD) in thyroid carcinoma has to be confirmed in large or multicenter prospective studies.

Humans↗
PubMed2001

[Acute coronary syndromes: an update. II. Coronary revascularization and risk stratification].

UNLABELLED: CORONARY REVASCULARIZATION: PTCA in patients with refractory unstable angina is associated with a substantial risk of the following complications: death, myocardial infarction, need for emergency surgery, and restenosis. The introduction of intracoronary stents, however, has improved both short-term and long-term outcomes. The newer adjunctive pharmacologic therapies enhance even further the benefits associated with the use of stents. The decision regarding the specific revascularization procedure to be used (e.g., CABG, PTCA, stent placement, or atherectomy) is based on the coronary anatomy, the left ventricular function, the experience of the medical and surgical personnel, the presence or absence of coexisting illnesses, and the preferences of both the patient and the physician. RISK STRATIFICATION: Among patients with unstable angina or non-Q-wave myocardial infarction, there is an increased risk of death within 6 weeks in those with elevated troponin I levels and the risk of death continues to increase as the troponin level increases. Reversible ST segment depression is associated with an increase by a factor of 3-6 in the likelihood of death, myocardial infarction, ischemia at rest, or provocable ischemia during a test to stratify risk. Exercise or pharmacologic stress testing provides important information about a patient's risk. Although the conditions of the majority of patients with unstable angina will stabilize with effective antiischemic medications, approximately 50-60% of such patients will require coronary angiography and revascularization because of the "failure" of medical therapy. High-risk patients are those who have had angina at rest, prolonged angina, or persistent angina with dynamic ST segment changes or hemodynamic instability, and they urgently require simultaneous invasive evaluation and treatment. Medical therapy should be adjusted rapidly to relieve manifestations of ischemia and should include antiplatelet therapy (aspirin, or ticlopidine or clopidogrel if aspirin is contraindicated), antithrombotic therapy (unfractionated heparin or low-molecular-weight heparin), beta-blockers, nitrates, and possibly calcium-channel blockers. Early administration of glycoprotein IIb/IIIa inhibitors may be particularly important, especially in high-risk patients with positive troponin tests or those in whom implantation of coronary stents is anticipated.

Acute Disease↗
PubMed2001

[Acute coronary syndromes: an update. I. Pathogenesis and drug therapy].

BACKGROUND: Unstable angina accounts for more than one million hospital admissions annually. 6-8% of patients with this condition have non-fatal myocardial infarction or die within the first year after diagnosis. Recently, the term "acute coronary syndromes" has been used to describe the spectrum of conditions that includes unstable angina, non-Q-wave myocardial infarction (which generally presents without ST-segment elevation), and Q-wave myocardial infarction (which generally presents with ST-segment elevation). PATHOGENESIS: Disruption of a formed plaque is a complex pathologic process that is central to the initiation of the acute coronary syndromes. Local thrombosis occurring after plaque disruption results from complex interactions among the lipid core, smooth-muscle cells, macrophages, and collagen. TREATMENT: Multiple huge clinical trials confirmed that aspirin reduces the risk of death from cardiac causes and fatal and non-fatal myocardial infarction by about 50-70% in patients presenting with unstable angina. Ticlopidine may be substituted for aspirin in patients with hypersensitivity to aspirin or gastrointestinal intolerance. Clopidogrel acts similarly to ticlopidin but has fewer side effects than ticlopidine and has not been reported to cause neutropenia. High-risk patients with refractory unstable angina and elevated troponin levels may have substantial benefit of glycoptotein (GP) IIb/IIIa inhibition. Current practice guidelines support the use of the combination of unfractionated heparin and aspirin for the treatment of unstable angina. Clinical studies have demonstrated that the incidence of the composite end point of death, myocardial infarction, or recurrent angina was lower with enoxaparin than with unfractionated heparin. Beta-blockers, nitrates, and calcium-channel blockers are useful for antiischemic therapy in patients with acute coronary syndromes.

Acute Disease↗
PubMed2001

In vivo recording of monophasic action potentials in awake dogs--new applications for experimental electrophysiology.

INTRODUCTION: Despite enormous developments in the field of clinical and experimental electrophysiology there is still a gap in evaluating repolarization in the awake animal. Numerous previous studies have used monophasic action potentials (MAP) to assess repolarization in vitro and in vivo in anesthetized animal models. However, an approach for recording MAP in awake dogs without interference of anesthesia has not yet been developed. METHODS AND RESULTS: We developed an experimental technique to record MAP in conscious dogs by means of conventional rubber introducers which were implanted into the internal jugular vein. In seven awake dogs, atrial as well as ventricular MAP were simultaneously measured without complications. Pacing thresholds were low and stable over time ranging from 0.2 to 4.0 mA. The MAP amplitudes ranged from 10 to 30 mV for ventricular and from 5 to 15 mV for atrial MAP. Continuous MAP recordings of stable amplitude could be made from the same endocardial site for periods of up to one hour. Antegrade and retrograde AV-nodal conduction properties could be assessed. Programmed stimulation was performed to simultaneously determine local refractory periods and MAP duration at cycle lengths from 500 to 200 ms. CONCLUSION: In awake, unsedated dogs the measurement of MAP via rubber introducers permits safe, long-term recording of MAP. Such recordings may be useful for safety pharmacological studies in evaluating cardiovascular and non-cardiovascular drugs with regard to their effects on repolarization. In various canine in vivo models including in vivo models of long QT syndrome, heart failure or sudden cardiac death, the present technique permits electrophysiological measurements without interference of anesthesia.

Action Potentials↗
PubMed2001

Familial occurrence of tardive dyskinesia.

OBJECTIVE: Familial occurrence of tardive dyskinesia (TD) and schizophrenia has been hypothesized to confer risk to the development of TD. We investigated these hypotheses in a large patient sample applying standardized methods for phenotype characterization. METHOD: Two hundred and twenty-two patients with a diagnosis of schizophrenia or schizoaffective disorder were assessed for TD and for family history of schizophrenia or schizoaffective disorder. Thirty-nine patients had 40 affected first-degree family members, one patient having two first-degree relatives. Of these, 17 pairs and one triplet were personally examined. RESULTS: 1) There was a tendency for TD in the affected relatives to be associated with the TD status of the index-patient; this finding was unrelated to age and doses of neuroleptic medication. 2) No association between a family history of schizophrenia or schizoaffective disorder and TD was found. CONCLUSION: A family history of TD might represent a risk factor for TD, whereas a family history of schizophrenia does not.

Adult↗
PubMed2001

Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men.

OBJECTIVE: Androgen replacement has been reported to increase bone mineral density (BMD) in hypogonadal men. We studied the effects of 6 months of treatment with a new transdermal testosterone (T) gel preparation on bone turnover markers and BMD. DESIGN: This was a prospective, randomized, multicentre, parallel clinical trial where 227 hypogonadal men, mean age 51 years (range: 19-68 years) were studied in 16 academic and research institutions in the USA. Subjects were randomized to apply 1% T gel containing 50 or 100 mg T (delivering approximately 5-10 mg T/day) or two T patches (delivering 5 mg T/day) transdermally for 90 days. At day 91, depending on the serum T concentration, the T gel dose was adjusted upward or downward to 75 mg T/day until day 180. No dose adjustment occurred in the T patch group. MEASUREMENTS: Serum T, free T and oestradiol, bone turnover markers and BMD were measured on days 0, 30, 90 and 180 before and after treatment. RESULTS: Application of T gel 100 mg/day resulted in serum T concentrations 1.4 and 1.9-fold higher than in the T gel 50 mg/day and the T patch groups, respectively. Proportional increases occurred in serum oestradiol. Urine N-telopeptide/creatinine ratio, a marker for bone resorption, decreased significantly (P = 0.0019) only in the T gel 100 mg/day group. Serum bone osteoblastic activity markers (osteocalcin, procollagen and skeletal alkaline phosphatase) increased significantly during the first 90 days of treatment without intergroup differences but declined to baseline thereafter. BMD increased significantly both in the hip (+1.1 +/- 0.3%) and spine (+2.2 +/- 0.5%) only in the T gel 100 mg/day group (P = 0.0001). CONCLUSIONS: Transdermal testosterone gel application for 6 months decreased bone resorption markers and increased osteoblastic activity markers for a short period, which resulted in a small but significant increase in BMD. Ongoing long-term studies should answer whether the observed increases in BMD are sustained or continue to be dependent on the dose of testosterone administered.

Administration, Cutaneous↗
PubMed2001

[Coronary artery bypass graft dysfunction--clinical presentation, laboratory and electrocardiographic parameters].

The recurrence of symptoms after coronary artery bypass surgery is often caused by bypass-dysfunction. In this study we tried to determine factors related to the long-term patency of arterial and venous bypass grafts. We evaluated all patients with bypass grafts undergoing coronary angiography in the year 1998 at our hospital (163 patients, mean age 67 years, mean interval since the operation 79 months, a total of 341 venous bypasses (VBP), 386 peripheral venous anastomoses and 85 arterial (LIMA = left internal mammarial artery) bypasses. The data were collected by a retrospective analysis of the hospital records. Statistics were performed using the Wilcoxon-Mann-Whitney-U test. After an interval of 53 months LIMA-bypasses were patent without stenosis in 92%. Symptoms were caused in only 2% by a dysfunction of the LIMA-graft. The patency of venous bypass grafts decreased with time (5 years after the operation 74% were patent without stenosis, 5-10 years 56%, more than 10 years 35%, p < 0.01). We found clear relations between the function of the venous grafts and the clinical presentation (patent grafts without stenosis in 43% with acute coronary syndromes, in 57% with stable angina [p = 0.08] and in 86% with atypical angina [p < 0.0001 for the difference between each of the first two and the last syndrome]), the resting-ECG (65% patent VBP without stenosis with normal ST-segments and 49% with abnormal ST-segments, p < 0.01), the body-mass-index (70% patent VBP without stenosis with a BMI < 25 and 56% with a BMI > 30, p = 0.05) and the erythrocyte sedimentation rate after 2 hours (79% patent VBP with an ESR < or = 20 mm vs. 64% with an ESR > 49 mm, p = 0.02). The function of VBP after coronary artery bypass graft (CABG)-procedure depends primarily upon the interval since the operation. In addition, we found correlations with clinical presentation, resting-ECG, body-mass-index and erythrocyte-sedimentation rate as a possible marker of inflammation in bypass-atherosclerosis. Therefore, inflammatory processes seem to play an important role in the development of venous graft dysfunction.

Aged↗
PubMed2001

[RC-Cornet(R) improves the bronchodilating effect of Ipratropiumbromide (Atrovent(R)) inhalation in COPD-patients].

In 35 patients with severe COPD and tracheal-bronchial instability the bronchodilatory effect of salbutamol (Salbulair(R) Autohaler) was tested prospectively, randomized and crossover on two consecutive days by bodyplethysmography. Following the salbutamol inhalation, the effect of ipratropiumbromide inhalation (by Pariboy and LC-plus-nebulizer) was evaluated in group A with an oscillating PEP-system (RC-Cornet(R), Position 1) in the expiratory outlet of the nebulizer and in group B with conventional inhalation by the Pari-system. The bronchodilatory effect was statistically significant better in group A inhaling ipratropiumbromide with the RC-Cornet(R) in the expiratory limb of the nebulizer in comparison to "normal" inhalation (decrease in airway resistance p < 0.0002, increase in vitacapacity p < 0.0051, increase in FEV1 p < 0.0161, Wilcoxon-Test for matched pairs). Using an oscillating PEP-system in the expiratory outlet of a nebulizer does not only increase the bronchodilatory effect of ipratropiumbromide but also shortens by combining inhalation and physiotherapy the time necessary for therapy in those patients.

Aged↗
PubMed2001

Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas.

BACKGROUND: This study evaluated the outcome of total thyroidectomy and modified radical neck dissection in primary treatment of patients with medullary thyroid carcinoma (MTC). METHODS: Thirty-six patients with sporadic (n = 16) and hereditary (n = 20) MTC underwent thyroidectomy and systematic central and lateral lymph node dissection (unilateral, 23; bilateral, 13) between 1994 and 2000. Postoperative serum calcitonin levels were correlated with immediate or delayed surgery, tumor categories, and lymph node metastases. RESULTS: Sixteen of 36 (44%) patients with clinically evident MTC treated with central and lateral neck dissection exhibited normal basal and stimulated calcitonin levels at a median follow-up of 3.7 years. Lymph node involvement was detected in 75% of these patients and correlated with the TNM stages. Biochemical cure was achieved according to the T categories in 83% of the patients in stage T1, 42% in stage T2, and none of the patients in stage T4 (P = .011). Basal and stimulated calcitonin levels were found to be normal in 89% of the patients without lymph node involvement and in 30% of the patients with lymph node metastases (P = .005). CONCLUSIONS: Screening for MTC and primary treatment with total thyroidectomy and modified radical neck dissection are essential for biochemical cure of MTC.

Adolescent↗
PubMed2001

Antibiotic-seeking behavior in college students: what do they really expect?

Injudicious use of antibiotics contributes to increased bacterial resistance, and patient expectations encourage physicians to overuse antibiotics. The authors evaluated the level of ill college students' antibiotic-seeking behavior to determine if receiving an antibiotic prescription influenced patients' satisfaction with visits to a clinician. Of 129 students with upper respiratory complaints presenting to a university health center, 55% expected an antibiotic prescription. Antibiotic expectation was significantly more likely among students who thought they had a bacterial versus a viral infection (90% vs 40%; p < .01). A clear diagnosis, an explanation of the rationale for treatment, and an antibiotic prescription were significantly associated with patient satisfaction. Clinicians prescribed an antibiotic for 36% of the students; only 13% of these 46 had requested an antibiotic during the visit. At some previous time, one third of the students had taken an antibiotic prescribed for an earlier illness or for another person. Better patient education and improved clinician-patient communication can potentially help to reduce the injudicious use of antibiotics.

Adolescent↗
PubMed2001

Immune response in progressive multifocal leukoencephalopathy: an overview.

Progressive multifocal leukoencephalopathy (PML) is a disease usually occurring in immunosuppressed patients. By far the most common underlying immunosuppressive illness is the acquired immune deficiency syndrome, accounting for about 85% of PML cases currently seen in clinical practice. PML may occur in patients with deficits in the humoral and/or cellular immune response such as lymphoproliferative diseases, myeloproliferative diseases, carcinomatous diseases and acquired immunodeficiency due to autoimmune diseases and immunosuppressive therapy. The humoral immune response in PML is indicative of a persistent, reactivated infection with a prominent immunoglobulin (lgG) G synthesis to virus protein 1 (VP1). An lgM synthesis in serum is rarely found. In about 76% of PML cases, an intrathecal humoral immune response to recombinant VP1 can be found as compared to only 3.2% in healthy controls. The detection of intrathecally synthesized lgG antibodies to VP1 can be used as an additional diagnostic test for the diagnosis of PML. The magnitude of the intrathecal humoral immune response appears to rise over time and may be associated with a decrease of viral load in cerebrospinal fluid (CSF) and possibly the central nervous system (CNS). Compared to healthy controls, proliferation of peripheral blood mononuclear cells (PBMC) is reduced in PML patients. Immunological studies suggest a general impairment of the Th1-type T-helper cell function of cell-mediated immunity. Furthermore, the appearance of JCV-specific cytotoxic T-lymphocytes appears to be associated with a favorable clinical outcome.

Antibody Formation↗
PubMed2001

Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements.

The vitamin E analog alpha-tocopheryl succinate (alpha-TOS) can induce apoptosis. We show that the proapoptotic activity of alpha-TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented alpha-TOS-triggered apoptosis. More selective effectors indicated that alpha-TOS reduced PKCalpha isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCalpha inhibition in alpha-TOS-induced apoptosis was confirmed using antisense oligonucleotides or PKCalpha overexpression. Gain- or loss-of-function bcl-2 mutants implied modulation of bcl-2 activity by PKC/PP2A as a mitochondrial target of alpha-TOS-induced proapoptotic signals. Structural analogs revealed that alpha-tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, alpha-TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.

Animals↗
PubMed2001

Effects of thoracic epidural anesthesia with and without autonomic nervous system blockade on cardiac monophasic action potentials and effective refractoriness in awake dogs.

BACKGROUND: The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. METHODS: The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. RESULTS: Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. CONCLUSIONS: This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

Action Potentials↗