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W Vogel

Publications and source records attributed to W Vogel.

At least 343 records · Page 19Linked to original sources

Evaluation of cytokines and cytokine-induced secondary messages in sera of patients after liver transplantation.

The study objective was first to investigate serum levels of tumor necrosis factor alpha, interleukin 1 beta, interferon gamma, interferon alpha, interleukin 2, beta-2-microglobulin (B2M), and urinary neopterin in patients after orthotopic liver transplantation; and second to relate their levels to clinical complications. The design used was the prospective observation study, and the setting used was the transplant unit of a university medical center. Serum samples were collected from 20 patients every alternate day from transplantation until discharge. The measurements and main results were as follows: concentrations of cytokines, B2M, and neopterin were performed using commercially available radioimmuno-assays. In seven out of nine patients with acute cellular rejections, elevated levels of TNF-alpha, IFN-gamma, IL-1, B2M, and neopterin were detected. The highest absolute levels of TNF-alpha were observed in patients with CMV disease. Increments in bacterial infections were comparable to those seen in the above-mentioned groups with the exception of IFN-gamma, which remained stable. IL-1 serum levels showed a different pattern with peak concentrations measured in sera before transplant and during rejection, while in the case of CMV disease levels gradually decreased. No detectable levels of IFN-alpha or IL-2 were observed. Our results indicate that enhanced endogenous production of TNF-alpha and IFN-gamma accompanied by elevated levels of B2M and neopterin represent a regular feature of inflammatory complications after liver transplantation. Serum cytokine levels however were not useful in distinguishing between rejection and infection. Evaluation of neopterin was more sensitive than cytokine or B2M measurement for the detection of inflammatory complications.

Adolescent↗

A K+ channel in Xenopus nerve fibres selectively blocked by bee and snake toxins: binding and voltage-clamp experiments.

1. The effects of mast cell degranulating peptide (MCDP), a toxin from the honey bee, and of dendrotoxin (DTX), a toxin from the green mamba snake, were studied in voltage-clamp experiments with myelinated nerve fibres of Xenopus. 2. MCDP and DTX blocked part of the K+ current. About 20% of the K+ current, however, was resistant to the toxins even in high concentrations. In Ringer solution half-maximal block was reached with concentrations of 33 nM-MCDP and 11 nM-DTX. In high-K+ solution the potency of both toxins was lower. beta-Bungarotoxin (beta-BuTX), another snake toxin, also blocked part of the K+ current, but was less potent than MCDP and DTX. 3. Tail currents in high-K+ solution were analysed and three K+ current components were separated according to Dubois (1981 b). Both MCDP and DTX selectively blocked a fast deactivating, slowly inactivating K+ current component which steeply activates between E = -60 mV and E = -40 mV (component f1). In concentrations around 100 nM, MCDP and DTX blocked neither the slow K+ current (component s) nor the fast deactivating, rapidly inactivating K+ current which activates between E = -40 mV and E = 20 mV (component f2). Similar results could be derived from K+ outward currents in Ringer solution. In high-K+, IC50 of MCDP for component f1 was 99 nM, whereas it was 7.6 microM for f2. Corresponding values for DTX are 68 nM and 1.8 microM. 4. Binding studies with nerve fibre membranes of Xenopus reveal high-affinity binding sites for 125I-labelled DTX (KD = 22 pM in Ringer solution and 81 pM in high-K+ solution). 125I-labelled DTX can be displaced from its sites completely by unlabelled DTX, toxin I (black mamba toxin), MCDP, and partially by beta-BuTX. 5. Immunocytochemical staining demonstrates that binding sites for DTX are present in nodal and paranodal regions of the axonal membrane. 6. The axonal membrane of motor and sensory nerve fibres is equipped with three types of well-characterized K+ channels and constitutes so far the best preparation to study MCDP- and DTX-sensitive K+ channels with electrophysiological and biochemical methods.

Animals↗

Visualization of DNA in pachytene by monoclonal antibodies against BrdU reveals synaptonemal complex-like structures.

Most of the techniques used to visualize structures of the synaptonemal complex (SC) are based on specific staining properties or immunocytochemical detection of proteinaceous SC components. The SC is therefore considered to be mostly protein. We have now accomplished visualization of the DNA within the SC by use of the BrdU antibody technique, following BrdU substitution during the last premeiotic S phase. Preparations of mouse meiotic chromosomes were obtained by spreading on a water surface. The DNA content in the SCs, which appeared as light threads, was clearly lower than the DNA content in the surrounding chromatin. At higher magnification, dark, longitudinal structures appeared in these threads. These structures are made up of DNA, which forms the inner part of the lateral elements of the SCs. Within the SCs, DNA is confined mostly to these threads. Thus, DNA staining reveals the same structures already known from protein staining of SCs. The DNA mass surrounding the SCs is often nonhomogeneously distributed along the chromosome axis. The more dense parts appear to be chromomeres. The DNA staining technique described in this paper may therefore be a useful complement to standard protein staining techniques for pachytene chromosomes.

Animals↗

[Pathogenesis of liver disease in alpha 1-antitrypsin deficiency].

Alpha-1-antitrypsin deficiency (A1ATD) is one of the most common lethal hereditary disorders. Approximately 5 to 10% of the general population carry an "at risk" gene for the development of liver disease or emphysema of the lung. Patients with A1ATD associated liver disease constitute a histologically and clinically heterogeneous group. The pathogenesis of the disease still remains to be elucidated. Recent experimental evidence produced in the transgenic mouse model is in favour of the engorgement hypothesis considering the deposition of amorphous A1AT in the hepatocytes the prime event causing liver disease. This theory, however, fails to explain the clinical observation of the presence of a number of other factors known to cause chronic liver disease in A1ATD patients. The latter observation is in support of the deficiency theory, which explains the pathogenesis of emphysema of the lung, and would point to A1ATD as a predisposition to acquire chronic disease. The meaning of the increased synthesis of stress proteins in patients with liver disease is still speculative.

Genetic Carrier Screening↗

[Third replacement of the tricuspid valve in combined aortic-tricuspid defect].

The implantation of valvular prostheses in tricuspid position is problematic due to the slow blood flow in the low-pressure system with the risk of valvular thromboses. Today there are prostheses with supportable low transvalvular gradients; nevertheless, the risk of valvular thromboses is, in spite of anticoagulation, increased by using mechanical prostheses in tricuspid position. We report on a 51-year-old woman in whom a dysfunction of the Starr Edwards ball prosthesis 15 years after its implantation in the tricuspid position was diagnosed. The prosthesis, which was unable to function due to connective tissue proliferation, was replaced by a St. Jude Medical prosthetic valve, which also presented a disturbed function a few days after the implantation. Because of a suspected valve thrombosis the patient was treated with rt-PA-lysis which proved to be ineffective. Thus it was inevitable to implant a third tricuspid valve; this time a bioprosthesis was used.

Aortic Valve↗

[Tumor markers in internal medicine hepatology].

Primary liver tumour, i.e. hepatocellular carcinoma (HCC) is one of the world's most common malignancies. The age-standardized incidence rate varies widely from 6/100,000 (Austria) to 100 and more per 100,000 in Mozambique and Taiwan. In these high-risk areas, infection with hepatitis B virus is considered the main risk factor. In low-incidence areas as in Western Europe, main risk factors are older age, male sex and liver cirrhosis. The prognosis depends mainly on the size of the tumour. Alpha-fetoprotein is an ideal tumour marker for prospective screening in high-incidence areas. There is not much information, however, on the value of this marker for screening in low-incidence areas. There is some information that HCC-associated alkaline phosphatase could be a good tumour marker in non-viral liver tumours. Furthermore, des-gamma-carboxyprothrombin and vitamin B 12-binding protein could be specific markers for tumours in non-cirrhotic livers. But large clinical studies have not yet confirmed the value of these markers. Hormonal and haematological markers and some isoenzymes are tumour markers characterized by high sensitivity but low specificity. There are no specific tumour markers for metastatic liver disease.

Biomarkers, Tumor↗

Occupancy of the iron-binding sites of human transferrin in sera obtained from different anatomical sites.

Transferrin is the major iron-transport protein in serum. Four molecular species (apo-, two mono-, and diferric transferrins) can be distinguished on the basis of their occupancy with iron. These species differ physicochemically and in the affinity with which they bind to the transferrin receptor. To elucidate the possible role of the four molecular species in directing the flow of iron between the major anatomical sites of iron release and utilization we have analyzed sera from eight stable multiorgan donors. The samples were obtained from veins draining the spleen, gut, and liver, and from the periphery. Employing polyacrylamide-gel electrophoresis in combination with crossed immunoelectrophoresis we were able to identify the four molecular species in all samples. Apo-transferrin was the predominant molecular species while diferric transferrin was the least abundant (P less than 0.01). The monoferric species were dominated by the acid-stable form (iron loading on the C-terminal end of the molecule) with ratios C/N from 1.2 (splenic and posthepatic serum) to 1.5-1.6 in mesenteric or peripheral samples respectively. We conclude from our study that it is unlikely that the monoferric transferrin species play a role in directing internal iron exchange and that in accordance with most of the literature the acid-stable form is preferentially loaded under physiological conditions of iron metabolism.

Adolescent↗

Sodium and potassium currents recorded during an action potential.

A simple method was used to measure directly sodium and potassium currents underlying the action potential in single nerve fibres of Xenopus laevis. A short rectangular stimulus under current-clamp conditions elicited an action potential which was digitally stored and later used as command when voltage-clamping the same fibre. The currents thus obtained nearly reproduced the original rectangular stimulus. Adding first 100 nM TTX and subsequently 100 nM TTX plus 10 mM TEA to the extracellular Ringer solution revealed the sodium and the potassium currents during an action potential. They were converted to permeabilities by use of the constant-field equation and are in good agreement with the curves which had been calculated from conventional voltage-clamp data. Thus experimentally determined currents and permeabilities are shown as they are changing during an action potential.

Action Potentials↗

How does inactivation change timing of replication in the human X chromosome?

The kinetics of replication of the inactive (late replicating) X chromosome (LRX) were studied in karyotypically normal lymphocytes and human amniotic fluid cells. Both cell types were successively pulse labeled with 1-h or 1/2-h thymidine pulses in an otherwise BrdU-substituted S phase after partial synchronization of the cultures at G1/S. For the first time with this technique, the entire sequence of replication was analyzed for the LRX from the beginning to the end of the S phase, with special reference to mid S (R-band to G-band transition replication). The inactive X is the last chromosome of the metaphase to start replication, with a delay of 1 or 2 h, after which time a thymidine pulse results in R-type patterns. In mid S, the inactive X is the first chromosome to switch to G-type replication (without overlapping of both types and without any detectable replication pause). Until the end of S, a thymidine pulse results in G-type patterns. To rule out artifacts that might arise by the synchronization of cultures in these experiments, controls were carried out with BrdU pulses and the BrdU antibody technique without synchronization. In the course of replication, no fundamental difference was seen between the two different cell types examined. In contrast to studies using continuous labeling, this study did not reveal an interindividual difference of replication kinetics in the LRXs of the seven individuals studied; thus it is concluded that the inactive X chromosome shows only one characteristic course of replication.

Amniotic Fluid↗

Analysis of chromosome replication by a BrdU antibody technique.

Chromosome replication was studied without synchronization in human lymphocyte and amniotic cell cultures visualizing very short 5-bromodeoxyuridine (BrdU) pulses by an immunologic technique (BAT). The findings agree in general with those facts known from earlier BrdU staining techniques. The very high sensitivity of BAT was shown to allow the detection of replication in a band where 1 in 200 nucleotides is replaced by BrdU. The main observations are: though the replication patterns after BAT appear strange the bands correspond to those described by the Paris Conference (1971). At the beginning of the S-phase a stepwise onset of replication in only a subset of R-bands is confirmed. There is a considerable difference in the sensitivity between early and late S (SE and SL) for the detection of BrdU pulses. This difference probably reflects a different spatial arrangement of chromatin in R-bands as compared with G-bands below the level of cytogenetic analysis. The use of short pulses did not reveal any additional subdivision of SE or SL. The correspondence between chromosomal bands and replicon clusters is discussed briefly with respect to the different time they need for replication.

Azure Stains↗

[Differential diagnostic importance of sonographically detected lymph node enlargement of the liver hilum in non-malignant liver diseases].

A total of 234 patients, 112 of whom were suffering from inflammatory liver disease and 122 from non-inflammatory liver disease were examined for enlarged lymph nodes in the hepatoduodenal ligament. Patients with malignancy were excluded from the study. In the 112 patients with inflammatory liver disease, enlarged lymph nodes in the hepatoduodenal ligament were demonstrated in 29 cases (25.9%). In cases with acute hepatitis (n = 25), lymphomas were seen in 18 examinations (72%). These enlarged lymph nodes disappeared when the liver enzymes fell to normal values. In patients with chronic inflammatory liver disease (n = 54), enlarged lymph nodes were found in only nine cases (16.7%). Of 27 "healthy" HBsAG-carriers, 26 were without lymph node enlargement. None of the patients without inflammatory, non-malignant liver disease showed lymph nodes in the hepatoduodenal ligament. Once malignancy is ruled out, lymphomas in the hepatoduodenal ligament should be considered an indication of inflammatory liver disease.

Diagnosis, Differential↗

Single-channel recording in myelinated nerve fibers reveals one type of Na channel but different K channels.

Amphibian myelinated nerve fibers were treated with collagenase and protease. Axons with retraction of the myelin sheath were patch-clamped in the nodal and paranodal region. One type of Na channel was found. It has a single-channel conductance of 11 pS (15 degrees C) and is blocked by tetrodotoxin. Averaged events show the typical activation and inactivation kinetics of macroscopic Na current. Three potential-dependent K channels were identified (I, F, and S channel). The I channel, being the most frequent type, has a single-channel conductance of 23 pS (inward current, 105 mM K on both sides of the membrane), activates between -60 and -30 mV, deactivates with intermediate kinetics, and is sensitive to dendrotoxin. The F channel has a conductance of 30 pS, activates between -40 and 60 mV, and deactivates with fast kinetics. The former inactivates within tens of seconds; the latter inactivates within seconds. The third type, the S channel, has a conductance of 7 pS and deactivates slowly. All three channels can be blocked by external tetraethylammonium chloride. We suggest that these distinct K channel types form the basis for the different components of macroscopic K current described previously.

Animals↗

Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis.

Liver transplantation provides a unique opportunity to investigate the contribution in vivo of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. We have determined the genetic polymorphisms plasma proteins. We have determined the genetic polymorphisms of apo A-IV, apo E, and of the Lp(a) glycoprotein (apo (a] in the plasma of subjects undergoing liver transplantation and in respective organ donors. The results show that in humans, greater than 90% of the plasma apo E and virtually all apo (a) are liver derived, whereas this organ does not significantly contribute to plasma apo A-IV levels.

Adolescent↗