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Biomedical subjects

F Weber

Publications and source records attributed to F Weber.

At least 127 records · Page 7Linked to original sources
PubMed1998

Synergistic immunomodulatory effects of interferon-beta1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing-remitting multiple sclerosis.

Subcutaneous application of interferon-beta1b (IFN-beta1b) is an established therapy for patients with relapsing-remitting multiple sclerosis (RRMS), but early side effects are still a major concern. In vitro studies with myelin basic protein (MBP)-specific T-cell lines revealed a synergistic suppressive effect of IFN-beta1b and the phosphodiesterase inhibitor pentoxifylline (PTX) on proliferation and the production of tumor necrosis factor-alpha (TNF-alpha), lymphotoxin (LT), and interferon-gamma (IFN-gamma). In an initial, open labeled prospective trial, the cytokine messenger RNA (mRNA) expression of blood mononuclear cells from MS patients, receiving either IFN-beta1b alone or in combination with oral PTX, was determined by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Patients treated with IFN-beta1b alone reported more side effects during the first 3 months of treatment and had upregulated TNF-alpha as well as IFN-gamma mRNA expression during the first month, which was not detected in patients receiving both drugs. A synergistic effect of both drugs was observed on the upregulation of interleukin (IL)-10 mRNA, which was accompanied by an increase in IL-10 serum levels. Both in vitro and in vivo data suggest that co-treatment of IFN-beta1b with PTX is a promising approach to correct the disturbed cytokine balance in MS patients.

Adjuvants, Immunologic↗
PubMed1998

[Reduced muscular oxygen tension and nerve impulse transmission from antishock hose. Reduction of oxygen tension in the tibial muscle and impulse transmission in the peroneal nerve from pneumatic -1 pressure from antishock hose].

OBJECT OF THE STUDY: The aim of the study was to assess, whether the pneumatic pressure of an antishock-trouser (AST) of 20-40 mm Hg induces a decreased oxygenation of the anterior tibial muscle and attenuates muscular response potential (MRP) of n. peronaeus profundus? METHODS: Among 22 normotensive, healthy volunteers the AST were tested by applying pressure values between 0 and 100 mm Hg and measuring the intracompartmental pressure, the muscular oxygen pressure as well as the MRP by electroneurographic means within a period of 6 hours. RESULTS: The median initial intracompartmental pressure value of the m. tibialis anterior was 12.0 mm Hg (Q25%/Q75%: 8.9/17.3), the muscular oxygen pressure 14.8 mm Hg (Q25%/Q75%: 11.5/22.0). Transmission of the pneumatic AST-leg segment pressure to the muscle: 97.7% (Q25%/Q75%: 89.2/99.8). Already in the low AST pressure field (20-40 mm Hg) a severe hypoxia occurred in one case. A reduction of MRP was noticed at an AST pressure rate of 10 mm Hg. In 5 of 6 cases AST pressure values of 60 mm Hg led to pathological pO2-values within 5-20 minutes. Almost without exception AST-pressure rates < 60 mm Hg resulted in an anoxia of the muscle and loss of the MRP. CONCLUSIONS: We should demand that the AST are only applied with models where the pressure generated within the single segments can be controlled by pressure gauge. The application of the AST seems to be justified for polytraumatised in severe haemorrhagic shock where the risk of a local tissue ischemia with systemical consequences must deliberately be accepted.

Adult↗
PubMed1998

Identification of macrophage populations expressing tumor necrosis factor-alpha mRNA in acute multiple sclerosis.

Macrophages are involved in central nervous system (CNS) demyelination in multiple sclerosis (MS) and other demyelinating diseases. Macrophages seen in MS lesions form a heterogeneous population with respect to their stage of activation and differentiation. We have analyzed macrophages from active demyelinating lesions of a patient who died from fulminant MS of Marburg's type to define the functional heterogeneity of different macrophage populations in acute demyelination. We examined tumor necrosis factor-alpha (TNF-alpha) mRNA expression in macrophages defined by different activation markers. The majority of TNF-alpha mRNA-positive cells were macrophages positive for the pan-macrophage marker KiM1P. A subgroup of TNF-alpha mRNA-positive macrophages was stained by the early activation marker MRP14. In contrast, macrophages positive for the acute activation marker 27E10 were entirely negative for TNF-alpha mRNA. In conclusion, macrophages in acute demyelinating CNS lesions are heterogeneous as shown by staining for different activation markers. This heterogeneity is also of functional relevance as certain subpopulations are involved in TNF-alpha mRNA expression, while others are not. This may be important for directing therapeutic strategies against well-defined pathogenic macrophage populations.

Acute Disease↗
PubMed1998

In vivo reconstitution of active Thogoto virus polymerase: assays for the compatibility with other orthomyxovirus core proteins and template RNAs.

Tick-borne Thogoto virus (THOV), the prototype of a new genus in the Orthomyxoviridae family, contains six single-stranded RNA segments of negative polarity. Four of them encode gene products that correspond to the influenza virus PB1, PB2, PA and NP core proteins. Here we describe an in vivo system in which the expression of a THOV model RNA is driven by THOV core proteins synthesized from cloned cDNAs. Our results demonstrated the biological activity of our cloned genes and showed that the three polymerase subunits and the NP are required for gene expression. For comparison, we also used the in vivo reconstituted systems of the influenza A and B viruses. None of the polymerase or NP proteins was active in a heterologous orthomyxovirus core, indicating a high specificity in core assembly and/or function. Interestingly, the THOV polymerase did not recognize the influenza A virus promoter and vice versa.

Cloning, Molecular↗
PubMed1998

The oligomeric structure of GroEL/GroES is required for biologically significant chaperonin function in protein folding.

Two models are being considered for the mechanism of chaperonin-assisted protein folding in E. coli: (i) GroEL/GroES act primarily by enclosing substrate polypeptide in a folding cage in which aggregation is prevented during folding. (ii) GroEL mediates the repetitive unfolding of misfolded polypeptides, returning them onto a productive folding track. Both models are not mutually exclusive, but studies with the polypeptide-binding domain of GroEL have suggested that unfolding is the primary mechanism, enclosure being unnecessary. Here we investigate the capacity of the isolated apical polypeptide-binding domain to functionally replace the complete GroEL/GroES system. We show that the apical domain binds aggregation-sensitive polypeptides but cannot significantly assist their refolding in vitro and fails to replace the groEL gene or to complement defects of groEL mutants in vivo. A single-ring version of GroEL cannot substitute for GroEL. These results strongly support the view that sequestration of aggregation-prone intermediates in a folding cage is an important element of the chaperonin mechanism.

Animals↗
PubMed1998

The diagnostic sensitivity of different F wave parameters.

OBJECTIVE: To examine the relative diagnostic sensitivity of various F wave parameters. METHODS: Normal values for minimum, mean, and maximum F wave latency, chronodispersion, and persistence in the four major motor nerves were established and systematically applied to at least four separate categories of patients (radiculopathies, polyneuropathies, mononeuropathies, and others). F Waves were studied both isolated and in comparison with other motor nerve conduction parameters. RESULTS: F Chronodispersion was the most often abnormal parameter, particularly in lumbosacral radiculopathies. Minimum F wave latency was more useful in polyneuropathies. Compared with minimum F wave latency, F chronodispersion was able to identify most additional cases. CONCLUSIONS: F Wave studies should include minimum F wave latency and chronodispersion.

Adult↗
PubMed1998

[Magnetic resonance imaging of tibial periostitis].

Tibial periostitis frequently occurs in athletes. We present our experience with MRI in a series of 7 patients (11 legs) with this condition. The clinical presentation and scintigraphic scanning suggested the diagnosis. MRI exploration of 11 legs demonstrated a high band-like juxta-osseous signal enhancement of SE and IR T2 weighted sequences in 6 cases, a signal enhancement after i.v. contrast administration in 4. Tibial periostitis is a clinical diagnosis and MRI and scintigraphic findings can be used to assure the differential diagnosis in difficult cases with stress fracture. MRI can visualize juxta-osseous edematous and inflammatory reactions and an increased signal would appear to be characteristic when the band-like image is fixed to the periosteum.

Adult↗
PubMed1997

Genetic predisposition to multiple sclerosis as revealed by immunoprinting.

This study was designed to examine the immunogenetic background predisposing to multiple sclerosis (MS). Three hundred fifty-eight clinically well-characterized MS patients from Germany were investigated and compared to 395 healthy control subjects. Each individual was genotyped for 22 polymorphic markers located within or close to immunorelevant candidate genes including HLA-DRB1*, T-cell receptor (TCR), cell interaction molecules, cytokines, and cytokine receptor genes. Altogether, approximately 17,000 genetic analyses were performed. Patients were grouped according to the course of MS-relapsing-remitting or chronic progressive. Most of the genetic markers were not associated with increased risk or their exact contribution was not clear (e.g., tumor necrosis factor). The relative risks for HLA-DRB1*15+ and DRB1*03+ individuals were 3.64 and 1.42, respectively. In both groups of patients, certain TCRB gene polymorphisms were risk factors. In DRB1*03+ individuals the relative risk was increased (> 22) when a specific TCRBV6S3 allele was also inherited. Furthermore, distinct linkage disequilibria of TCRBV6S1/TCRBV6S3 elements in patients and control subjects strongly suggested an additional risk factor in the TCRBV region for DRB1*15+ individuals. These findings are discussed with respect to the pathogenesis and rational approaches to the therapy of MS.

Adolescent↗
PubMed1997

Conserved vRNA end sequences of Thogoto-orthomyxovirus suggest a new panhandle structure.

Panhandles are dsRNA structures formed by conserved sequences at the 5' and 3' ends of the influenza virus genomic RNA. They consist of two stems separated by a flexible bulge and serve as promoter for the viral polymerase. In the outer stem, melting of base pairs is a prerequisite for initiation of transcription. We compared the terminal sequences of Thogoto virus (THOV), a tick-borne orthomyxovirus, with those of influenza virus. Despite their overall similarity, the first U downstream of the 5' end of the panhandle (position 3 in influenza virus) is found at position 8 in the THOV sequence. This shift from position 3 to position 8 results in a radical change of the predicted secondary structure. In the outer stem, intra-strand base pairings are clearly favoured above inter-strand hybridizations. As this secondary structure can explain the functioning of a mutant promoter of influenza virus with twice the activity of the wild-type, we propose a general validity of our "hook-like" panhandle structure.

Base Sequence↗
PubMed1997

The fourth genus in the Orthomyxoviridae: sequence analyses of two Thogoto virus polymerase proteins and comparison with influenza viruses.

The tick-borne Thogoto virus (THOV) is the type species of a newly recognized fourth genus, Thogotovirus, in the family Orthomyxoviridae. Because of the distant relationship of THOV with the influenza viruses, determination of its genomic information can potentially be used to identify important domains in influenza virus proteins. We have determined the complete nucleotide sequence of the second longest RNA segment of THOV. The molecule comprises 2212 nucleotides with a single large open reading frame encoding a protein of 710 amino acids, estimated Mr 81,284. The protein shares 77% amino acid similarity with the PB1-like protein of Dhori virus, a related tick-borne virus, and 50-53% with the PB1 polymerase proteins of influenza virus A, B and C. All the motifs characteristic of RNA-dependent polymerases were identified including the SSDD motif common to all RNA-dependent RNA polymerases, indicating that the THOV protein is functionally analogous to the influenza virus PB1 proteins and involved in chain elongation. We also report the corrected sequence of the third longest RNA segment of THOV, encoding a protein which shares 44-47% amino acid similarity with the PA-like polymerase proteins of influenza virus A, B and C. The biological significance of conserved domains in these orthomyxovirid proteins is discussed.

Amino Acid Sequence↗
PubMed1997

Misoprostol in the treatment of chronic refractory constipation: results of a long-term open label trial.

BACKGROUND: Misoprostol is known to be effective in stimulating intestinal transit both in healthy individuals and in patients with chronic constipation when evaluated in short-term trials. The aim of this study was to determine the utility of misoprostol in the long-term management of patients with chronic refractory constipation. METHODS: Eighteen patients were offered misoprostol (600-2400 microg/day) as adjunctive therapy in an open-ended, non-blinded trial. All patients were encouraged to continue the drug for a minimum of 4 weeks, after which time the effect on bowel movement patterns was evaluated and continued use of misoprostol was offered to those patients who demonstrated a clinical benefit. RESULTS: Six patients withdrew prior to 4 weeks because of side-effects. In the 12 patients who continued the treatment and were evaluated at 4 weeks, the mean interval between bowel movement frequency had decreased from a baseline of 11.25 to 4.8 days (P = 0.0004). Eight patients continued the long-term treatment, with sustained response seen in six. In a subset of patients (n = 4) the effect of single-dose misoprostol (400 microg) was evaluated compared to healthy controls (n = 5) on post-prandial segmental colonic motility. Misoprostol augmented the colonic motility response to a meal throughout the colon, and this was significantly greater in the left versus right colonic segments (P < 0.05). CONCLUSIONS: Misoprostol can be effective as part of the long-term medical treatment of patients with chronic refractory constipation, but side-effects are observed at higher doses and can be a limiting factor. Part of misoprostol's action may be mediated through the augmentation of colonic motility, particularly of the left colon.

Adult↗
PubMed1997

Mx1 sensitivity: Batken virus is an orthomyxovirus closely related to Dhori virus.

Batken virus, isolated from mosquitoes and ticks, was tentatively classified as a member of the family Bunyaviridae. Here we show that Batken virus is inhibited by the interferon-induced Mx1 protein of mice which selectively blocks the growth of orthomyxoviruses, including Thogoto and Dhori viruses. Furthermore, we show that Batken virus multiplication is characterized by accumulation of viral proteins in the nucleus and by budding of viral particles from the cell surface. Serological cross-reactions between Batken and Dhori viruses revealed a phylogenetic relationship of these viruses, as previously also proposed by D. K. Lvov. Fragments of the Batken virus glycoprotein and nucleoprotein genes were amplified by RT-PCR. The deduced amino acid sequences were similar to the corresponding Dhori virus sequences. Therefore, Batken virus should be classified into the newly established genus Thogotovirus of the family Orthomyxoviridae. Finally, our results demonstrate that Mx1 susceptibility of orthomyxoviruses is a reliable marker in the hunt for new family members.

Amino Acid Sequence↗
PubMed1997

The cost and benefit of prophylaxis against deep vein thrombosis in elective hip replacement. DVT/PE Prophylaxis Consensus Forum.

UNLABELLED: A consensus forum was convened to evaluate the economic considerations associated with prophylaxis against thrombo-embolic disease in patients undergoing hip replacement therapy in South Africa. This forum consists of orthopaedic surgeons, vascular surgeons and a statistician. METHODS: The forum was instructed to evaluate the economic costs of the commonly used forms of prophylaxis of thrombo-embolism in patients undergoing hip replacement surgery in South Africa, looking at short-term events only. The methods used for the prophylaxis of thrombo-embolism in South Africa were determined by a postal survey. A decision tree was constructed to determine the events that will occur after a clinical decision to use no prophylaxis. The probabilities of these events were then determined. Protocols for and costs of prophylaxis and treatment were established. With the decision tree and these costs, the cost of the various modalities of prophylaxis was then determined. RESULTS: The probability, determined by the forum, of developing a deep-vein thrombosis (DVT) when no prophylaxis is used was 0.5, with a mortality rate of 2.1%. The cost of this decision was R875. No prophylaxis given, but a venogram performed on day 7, reduced the mortality rate to 0.7%; however, this cost R3 017. The cost of low-molecular-weight heparin was R1 223 (probability 0.26, mortality rate 1.1%), while unfractionated heparin with a graduated compression stocking (GCS) cost R1 351 (probability 0.24, mortality rate 1%). Aspirin with a GCS cost R777 (probability 0.35, mortality rate 1.5%).

Anticoagulants↗
PubMed1997

Conduction block and abnormal temporal dispersion--diagnostic criteria.

Conduction block and abnormal temporal dispersion are important electrophysiological parameters for demyelination. As criteria for conduction block a more than 20% drop in the peak-to-peak amplitude with less than a 10% change in the negative-peak duration has been proposed. In order to check the validity of these criteria, the amplitude, duration and area of the compound muscle action potentials (CMAP) were studied in 50 normal persons. In these normal subjects there was a substantial difference in the degree of CMAP amplitude and area reduction and CMAP duration prolongation with proximal stimulation among the various nerves. Particularly the posterior tibial nerve showed the highest values for amplitude drop and for dispersion, which is most likely due to the inherent technical difficulty of stimulation at the popliteal fossa. Thus, different criteria should be used for conduction block or abnormal temporal dispersion for a given nerve. If a single value must be used as a criterion for all nerves, 50% for conduction block and 30% for abnormal temporal dispersion is recommended.

Action Potentials↗
PubMed1996

Mechanism of chaperonin action: GroES binding and release can drive GroEL-mediated protein folding in the absence of ATP hydrolysis.

As a basic principle, assisted protein folding by GroEL has been proposed to involve the disruption of misfolded protein structures through ATP hydrolysis and interaction with the cofactor GroES. Here, we describe chaperonin subreactions that prompt a re-examination of this view. We find that GroEL-bound substrate polypeptide can induce GroES cycling on and off GroEL in the presence of ADP. This mechanism promotes efficient folding of the model protein rhodanese, although at a slower rate than in the presence of ATP. Folding occurs when GroES displaces the bound protein into the sequestered volume of the GroEL cavity. Resulting native protein leaves GroEL upon GroES release. A single-ring variant of GroEL is also fully functional in supporting this reaction cycle. We conclude that neither the energy of ATP hydrolysis nor the allosteric coupling of the two GroEL rings is directly required for GroEL/GroES-mediated protein folding. The minimal mechanism of the reaction is the binding and release of GroES to a polypeptide-containing ring of GroEL, thereby closing and opening the GroEL folding cage. The role of ATP hydrolysis is mainly to induce conformational changes in GroEL that result in GroES cycling at a physiologically relevant rate.

Adenosine Diphosphate↗