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Biomedical subjects

F Weber

Publications and source records attributed to F Weber.

At least 145 records · Page 8Linked to original sources
PubMed1996

Gene polymorphism at position -308 of the tumor-necrosis-factor-alpha (TNF-alpha) in multiple sclerosis and it's influence on the regulation of TNF-alpha production.

Tumor-necrosis-factor alpha (TNF-alpha) is a major mediator of the inflammatory immune response and may play an important role in the pathogenesis and progression of Multiple Sclerosis (MS). Increased TNF-alpha levels of cerebrospinal fluid (CSF) and peripheral blood were found in patients with chronic progressive MS and patients with acute relapses, but not in the stable form of the disease. Considering the association of different TNF-alpha alleles with diverse autoimmune diseases we sequenced the TNF-alpha promotor region (-674 to +201) of 23 patients with relapsing/remitting MS, of 27 patients with chronic progressive MS (21 patients had primary progressive course and six patients had a secondary progressive course) and of 22 healthy controls, who had no history of MS in their families. In three of 21 patients (14%) with primary chronic progressive MS a homozygous point-mutation at position -308 could be demonstrated where guanine (G) was substituted by adenosine (A). This mutation could neither be detected in patients with relapsing/remitting MS nor in healthy controls. However, 40% of the patients with relapsing/remitting MS and 43% of the primary chronic progressive MS patients were heterozygous at position -308 for G/A, whereas only 32% of healthy controls showed this heterogeneity. The genetic variations were demonstrated by polymerase chain reaction (PCR)-amplification of the TNF-alpha promotor-region and consecutive direct automatic sequencing. Functional analysis of the promoter region using the chloramphenicol-acetyltransferase (CAT) assay revealed spontaneous production with the homozygous mutation at -308 only.

Adenosine↗
PubMed1996

Simultaneous Measurement of Local Gain and Electron Density in X-ray Lasers

X-ray lasers (XRLs) have experimental average gains that are significantly less than calculated values and a persistently low level of spatial coherence. An XRL has been used both as an injected signal to a short XRL amplifier and as an interferometer beam to measure two-dimensional local gain and density profiles of the XRL plasma with a resolution near 1 micrometer. The measured local gain is in agreement with atomic models but is unexpectedly spatially inhomogeneous. This inhomogeneity is responsible for the low level of spatial coherence observed and helps explain the disparity between observed and simulated gains.

Journal Article↗
PubMed1996

The role of adjuvant radiation and multiple resection within the surgical management of brain metastases.

Cerebral metastases occur in 25% to 35% of all cancer patients. The advances in systemic and topical treatment as well as the rising incidence of lung cancer and melanomas are associated with an increasing incidence of cerebral metastases. More than 20,000 patients die every year in the Federal Republic of Germany of this disease. This retrospective analysis covers 145 patients who underwent surgery. Survival analysis of different subgroups was performed. The patients were grouped according to their clinical status and the different therapeutical procedures which were performed. Group A, consisting of all those patients where a gross total resection could be performed and where no systemic disease was apparent at the time of craniotomy showed the best results, having the highest portion of long term survivors. Group B, consisting of those patients who underwent a subtotal resection and who had no systemic disease at the time of craniotomy, had a worse outcome. Group C patients (gross total resection and systemic disease) as well as Group D (subtotal resection and systemic disease) presented the poorest results with respect to survival. A benefit was mediated by adjuvant radiation as well as multiple resections. Surgery is the method of choice for the treatment of a single metastasis. Advances in microsurgery nowadays sometimes justify even the removal of multiple metastases, depending on their location, on the general condition of the patient and on prognosis.

Adult↗
PubMed1996

Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis.

The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.

Autoimmune Diseases↗
PubMed1996

Nucleoprotein viral RNA and mRNA of Thogoto virus: a novel "cap-stealing" mechanism in tick-borne orthomyxoviruses?

Tick-borne Thogoto virus (THOV) represents the prototype virus of a new genus in the Orthomyxoviridae family. Its genome consists of six segments of negative-sense, single-stranded RNA. We have cloned and sequenced the fifth genomic segment, which codes for the viral nucleoprotein (NP). The deduced amino acid sequence shows 43% similarity to the NP of Dhori virus, a related tick-transmitted orthomyxovirus, and about 14% sequence similarity to those of the influenza viruses. To reveal the mechanism by which THOV initiates mRNA synthesis, we characterized the 5' ends of the NP mRNAs. Transcripts were recognized by a cap-specific monoclonal antibody, indicating that THOV mRNAs are capped. Surprisingly, no large heterogeneous extensions were found at the 5' end, as would have been expected if THOV were using a classical "cap-stealing" mechanism. We therefore propose that THOV is stealing only the cap structure with one or two additional nucleotides from cellular mRNAs to generate appropriate primers for initiation of viral mRNA transcription.

Amino Acid Sequence↗
PubMed1996

The challenge of changing healthcare systems.

Healthcare systems are in flux throughout the world. Traditional structures and attitudes are changing. The balance of power between political bodies, payers, providers and patients is being destabilised. New approaches by governments and forward integration by drug companies and payers into care management are all major changes from the past. In the future, healthcare providers, particularly hospitals, will have to complement medical with business skills to survive in a more competitive environment. Experience shows that there is major potential for improvement in terms of radical rethinking of how care is provided (e.g. at least a 30% reduction in hospital days per insured life together with quality-of-care improvements). In particular, the economic value of changes in treatment (e.g. ambulatory surgery, switch to home therapy) should be understood and optimised. In a new world scenario, payers and providers will shape the healthcare environment by introducing novel approaches and integrating healthcare delivery. This process, coupled with the introduction of new approaches to competition and risk sharing by the government, could cause the emergency of high performance and more cost-effective healthcare systems.

Delivery of Health Care↗
PubMed1996

[Dangerousness prognosis in the clinical context of fulfillment of psychiatric criminal commitment].

The compilation and the reliability-based evaluation of the questionnaire including potentially prognosis-relevant clinical criteria for the release of male patients from rehabilitation and security measure (section 63 German Criminal Code) are presented. The restriction to clinical (rather than social statistical) criteria results in a concentration of the criminal aspects of treatment and/or therapy. The open and, more importantly, the "unconscious" focuses of forensic clinical action become transparent. However, the prognostic constructs of clinicians prove to be somewhat lacking in criteria and rather inconsistent. Until it is validated as a prognostic instrument and integrated in a multidimensional inventory of prognoses, this questionnaire can contribute towards conceptual transparency and help create a better link between treatment and release criteria.

Adult↗
PubMed1995

[Measuring blood pressure at the wrist: critical analysis of a validation study].

BACKGROUND: The new device "Blood Pressure Watch" (BPW) by NAIS-Matsushita, which measures blood pressure oscillometrically at the hand wrist, is preferred by many hypertensive patients as a device for self-measurements because of its smallness and simple applicability. SUBJECTS AND METHOD: To evaluate the accuracy of blood pressure measurements with this device we determined the blood pressure four times consecutively in the aortic arch using a Statham P23 and the BPW simultaneously at the left hand wrist in 27 patients (58.6 +/- 10.3 [range: 36 to 76] years; 21 male) after a coronary angiography. RESULTS: With a correlation coefficient of 0.85 for systolic and 0.84 for diastolic pressure mean blood pressure was determined higher (systolic: +1.4 +/- 10.1 mm Hg, diastolic: +4.4 +/- 7.6 mm Hg) by the BPW compared to the aortic arch pressure. While there was no correlation between systolic differences and patients' age, it could be demonstrated that with increasing age the BPW exhibited higher diastolic blood pressure values than those measured in the aortic arch. Multiple regression analysis revealed that this was due to inability of the BPW to detect low diastolic blood pressures (r = 0.89, p < 0.001). CONCLUSIONS: 1. For the majority of hypertensive patients the hand wrist device is suitable for self-measurement of blood pressure. It is advisable to perform an auscultatory comparative test at least once before buying such a device. 2. The oscillometric method for measuring blood pressure does not seem to be the proper method for epidemiologic studies and investigation of population groups in which lower diastolic pressure ranges are to assumed.

Adult↗
PubMed1995

[Tuberous sclerosis: typical complications of a hereditary disease and therapeutic options].

BACKGROUND: Tuberous sclerosis is an autosomal-dominant hereditary disease (incidence and prevalence 1:10,000) which is characterized by hamartomas in various organs. PATIENTS AND METHODS: We demonstrate three patients with different and partly atypical manifestations: All had facial angiofibroma. No patient was mentally retarded and epilepsy was observed only intermittently. In all cases periventricular calcifications were noted and renal angiomyolipomas were found. Two patients requested dialysis after nephrectomy. One patient suffered from severe complications of the rare pulmonary lymphangioleiomyomatosis. RESULTS: Therapy of this multiorgan disease is only symptomatic. Operations should be considered as second line treatment. In one case, successful renal transplantation is described. CONCLUSIONS: Genetic counselling is warranted in this disease with high penetrance, particularly the broad spectrum of manifestations should be taken into account.

Adult↗
PubMed1995

[Type I cryoglobulinemia].

HISTORY AND CLINICAL FINDINGS: For 2 years a 52-year-old man had repeated bouts of purpura, arthralgia and fever. He was known to have abnormal monoclonal gammaglobulins, type IgG-lambda and vasculitis when he had another bout with acute renal failure and necrotizing ulcers in the legs. TESTS: Several laboratory tests were abnormal: erythrocyte sedimentation rate (122 mm), haemoglobin level (9.1 g/dl), white cell count (32,000/microliters), platelet count (562,000/microliters), creatinine level (4.1 mg/dl) and liver enzyme activities. He also had proteinuria (4.5 g daily) and nephritic urinary sediments. The immunoglobulin was subtype IgG3, and a cryoglobulinaemia was also present. Total complement level (CH 50) was not measurable. Bone marrow aspirate revealed plasmocytoma infiltration, and renal biopsy demonstrated necrotizing arteritis, as well as granular subendothelial deposits of IgG and complement. TREATMENT AND COURSE: After three plasma separations and initiation of the first treatment cycle with a four-day infusion of vincristine, doxorubicin and dexamethasone the creatinine concentration fell to within the normal range and the necroses healed slowly. No cryoglobulin activity has been demonstrable over the past 24 months.

Acute Kidney Injury↗
PubMed1995

Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression.

We recently characterized (Moebius, F. F., Burrows, G. G., Striessnig, J., and Glossmann H. (1993) Mol. Pharmacol. 43, 139-144) and purified (Moebius, F. F., Hanner, M., Knaus, H. G., Weber, F., Striessnig, J., and Glossmann, H. (1994) J. Biol. Chem. 269, 29314-29320) a binding protein for the phenylalkylamine Ca2+ antagonist emopamil. The emopamil-binding protein (EBP) acts as a high affinity acceptor for several antiischemic drugs and thus represents a potential common molecular target for antiischemic drug action. Degenerate oligonucleotides were synthesized according to the N-terminal amino acid sequence of purified EBP and used to amplify a guinea pig cDNA with reverse transcriptase-polymerase chain reaction and to clone full-length cDNAs from guinea pig and human liver cDNA libraries. The cDNAs coded for 229 (guinea pig) and 230 (human) amino acid 27-kDa polypeptides without significant sequence homology with any known protein. However, EBP shared structural features with pro- and eukaryotic drug transport proteins. The amino acid identity between human and guinea pig EBP was 73%. Hydrophobicity plots predicted four transmembrane segments. The C terminus contained a lysine-rich consensus sequence for the retrieval of type I integral membrane proteins to the endoplasmic reticulum. The heterologous expression of human and guinea pig EBP in Saccharomyces cerevisiae demonstrated that the expression of EBP alone is sufficient to form high affinity drug- and cation-binding domains identical to the [3H]-emopamil-binding site of guinea pig liver. Northern and Western blot analysis revealed high abundance of EBP in guinea pig epithelial tissues as liver, bowel, adrenal gland, testis, ovary, and uterus and low densities in brain, cerebellum, skeletal muscle, and heart. EBP is suggested to be the first structurally characterized member of a family of high affinity microsomal drug acceptor proteins carrying so called sigma-binding sites.

Amino Acid Sequence↗
PubMed1995

Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells.

Lymphotoxin (LT) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the pathogenesis of multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. Because both LT and TNF-alpha are encoded in the HLA region, the HLA association of MS may be related to the production of these cytokines. To test this hypothesis, we investigated the production of LT, TNF-alpha, and interferon-gamma (IFN-gamma) by CD4+ T-cell lines (TCLs) specific for myelin basic protein (MBP) or tetanus toxoid (TT) isolated from MS patients and normal controls. After stimulation with specific antigen but not mitogen, TCLs from HLA-DR2+ donors produced significantly more LT and TNF-alpha than TCLs from DR2- donors. In contrast, HLA-DR2+ and DR2- TCLs did not differ in the production of IFN-gamma, a cytokine also produced by T cells but not encoded in the HLA region. Increased secretion of LT and TNF-alpha was unrelated to the specificity (MBP vs TT), MHC restriction (HLA-DR2 vs other DR molecules), or source (MS vs normal) of the TCLs. There was no significant association of the cytokine production with individual LT or TNF-alpha alleles, indicating that the increased production of these cytokines may be linked to other polymorphic genes in this region. The results suggest that the association of MS with HLA-DR2 implies a genetically determined propensity of T cells to produce increased amounts of LT and TNF-alpha.

Animals↗
PubMed1995

[EEG changes during sedation with gamma-hydroxybutyric acid].

Gamma-hydroxybutyric acid (GHB) is a naturally occurring transmitter in the mammalian brain, related to sleep regulation and possibly to energy balance in diving or hibernating animals. It has been used for almost 35 years as an intravenous agent for induction of anaesthesia and for long-term sedation. Its convincing pharmacological properties, without serious adverse effects on circulation or respiration, are compromised by its unpredictable duration of action. This is not a major problem with long-term sedation during ICU treatment. GHB has been used with good results for sedation of patients with severe brain injury, where it compares favourably with barbiturates. In animal studies, it seems to possess a protective action against hypoxia on a cellular and whole organ level. However, in some experimental animals GHB has been shown to produce seizure-like activities, and the compound is being used to produce absence-like seizures. GHB has been used in our ICU for years to provide adequate sedation for patients under controlled ventilation or for patients fighting the respirator during spontaneous respiration. No serious side effects were observed in these patients, while in some patients under haemodialysis hypernatraemia and metabolic alkalosis developed; both were reversible after discontinuation of GHB and restriction of additional sodium input (Somsanit, the commercially available GHB preparation in Germany, contains 9.2 mmol sodium/g; the daily dose averages 20-40 g GHB, i.e. 180-370 mmol sodium). PATIENTS AND METHODS. In 31 patients after major abdominal surgery, sedation was established with GHB 50 mg/kg BW injected via perfusion pump over a 20-min period. No centrally acting medication had been given for at least 2 h. A computer-based multichannel EEG system (CATEEM, MediSyst, Linden) was used, allowing for fast Fourier transformation, spectral analysis and topographical brain mapping. EEG during induction of sedation was followed after a baseline EEG (10 min) had been recorded. Patients receiving long-term sedation were studied daily for an additional 15-min period. Corresponding well to the clinical findings, EEG pattern changed to a slow delta-theta or delta-only rhythm within 10 min of the start of injection. Alpha and beta power decreased, while delta activity exhibited an increase. All changes were most obvious in frontal and central areas of the brain. In about one out of three patients, a burst--suppression pattern developed. Since automatic processing of EEG may fail to detect special patterns like the looked-for 3/s spikes and waves, the raw EEG was analysed visually by an expert neurologist. Both processed and conventionally analysed EEG were free of any seizure-like electrical activity. CONCLUSION. We conclude that animal data may not apply to the use of GHB in humans, provided the dose is limited to the clinical needs. GHB is used in clinical practice in doses twice as high, or even higher, than the one we use for induction, without obvious side effects. However, the suppression of theta rhythm we observed in about half of the patients studied may indicate that even less than 50 mg/kg BW might be sufficient for adequate sedation.

Abdomen↗