Biomedical subjects

H Barth

Publications and source records attributed to H Barth.

At least 55 records · Page 3Linked to original sources

PubMed2000

Binding of Clostridium botulinum C2 toxin to asparagine-linked complex and hybrid carbohydrates.

Clostridium botulinum C2 toxin is a binary toxin composed of an enzymatic subunit (C2I) capable of ADP-ribosylating actin and a binding subunit (C2II) that is responsible for interaction with receptors on eukaryotic cells. Here we show that binding of C2 toxin depends on the presence of asparagine-linked carbohydrates. A recently identified Chinese hamster ovary cell mutant (Fritz, G., Schroeder, P., and Aktories, K. (1995) Infect. Immun. 63, 2334-2340) was found to be deficient in N-acetylglucosaminyltransferase I. C2 sensitivity of this mutant was restored by transfection of an N-acetylglucosaminyltransferase I cDNA. C2 toxin sensitivity was reduced after inhibition of alpha-mannosidase II. In contrast, Chinese hamster ovary cell mutants deficient in sialylated (Lec2) or galactosylated (Lec8) glycoconjugates showed an increase in toxin sensitivity compared with wild-type cells. Our results show that the GlcNAc residue linked beta-1,2 to the alpha-1,3-mannose of the asparagine-linked core structure is essential for C2II binding to Chinese hamster ovary cells.

Animals↗

PubMed2000

Giant cystic craniopharyngiomas with extension into the posterior fossa.

Between 1991 and 1998, 24 patients underwent surgery for a craniopharyngioma in our department. This group included two patients who had tumors with extensive growth along the midline, and along the posterior fossa in particular. In both cases suprasellar calcifications were typical features on magnetic resonance imaging (MRI) and computed tomography (CT). A 7-year-old boy presented with a 6-month history of headache, nausea, and progressive unilateral hearing loss. With a suboccipital approach it was possible to remove the main part of the tumor. In a 13-year-old boy headache and visual deterioration led to the diagnosis of a craniopharyngioma, which was removed with a pterional approach. For the neuroimaging work-up in such cases of atypically growing craniopharyngiomas MRI is the method of choice. Additional CT scanning is recommended, which provides valuable information about bony changes at the skull base due to space-occupying growth. CT substantiates the differential diagnosis if typical calcifications are seen.

Adolescent↗

PubMed2000

Spontaneous intracranial haematomas caused by neoplasms.

We report about 50 patients with spontaneous intracerebral haematomas (ICH) caused by intracranial neoplasms to assess the underlying histological condition, their presentation on admission, diagnostic work-up, treatment, histological diagnosis, and clinical outcome. These patients were identified in a prospective series of 2041 patients with intracranial neoplasms and 692 patients with spontaneous ICH, which were both consecutively collected over a nine-year-period. The frequency of ICH in patients with intracranial neoplasms was 2.4%. The frequency of tumour related ICH in the ICH group was 7.2%. The leading cause of tumour related ICH were metastases of extracranial origin (n = 18; 36%), followed by glioblastoma multiforme (n = 15; 30%). Nine patients (18%) had benign primary intracranial neoplasms. On admission 18 patients were somnolent (36%) and 14 patients (28%) were comatose. In 29 cases (58%) ICH was the first clinical sign of neoplastic disease, while in 21 patients (42%) a malignant tumour was already known. We operated on 45 patients (90%), four patients (8%) were not operated on because of poor clinical condition and died, one patient refused surgical treatment. Six patients (12%) died despite surgery. This series confirms the importance of a proper neuroradiological and clinical work-up of patients with suspected tumour related ICH followed by operative treatment and histological confirmation of the diagnosis. This is supported by the fact that 18% of patients had prognostically favourable intracranial tumours which would not otherwise have been adequately treated.

Acute Disease↗

PubMed2000

Three-dimensional (3-D) ultrasonography for obtaining the four and five-chamber view: comparison with cross-sectional (2-D) fetal sonographic screening.

OBJECTIVES: To assess the ability of Doppler-gated 3-D fetal echocardiography to reconstruct and display specific cardiac structures routinely visualized during antenatal ultrasound in a population at low risk for cardiac anomalies. To determine whether any advantage is offered by 3-D sonographic cardiac examination over conventional sonographic fetal screening techniques. DESIGN: After routine two-dimensional sonographic examination, 3-D cardiac data were collected prospectively in 30 fetuses with gestational ages between 19 and 23 weeks from a low risk patient population. Basic echocardiographic key views were derived from 3-D data and selected for reconstruction and analysis. Four- and five-chamber views were rated and only those views judged to be well visualized were considered as positive results. RESULTS: The four- and five-chamber views were well visualized in all but one fetus using conventional 2-D imaging. Gated 3-D volume data sets enabled visualization of these structures in only 19 of 30 fetuses but provided additional structural depth and allowed a dynamic 3-D perspective of valvar morphology and ventricular wall motion. The right ventricular outflow tract was available from the 3-D volumes in 16 subjects. CONCLUSIONS: Considering the versatility of gated 3-D fetal cardiac imaging we believe that it may soon become an important component of fetal screening thus helping to retrieve standard cardiac cross sections when 2-D imaging is limited by lack of sonographer experience or sonographic windows. Diagnostically acceptable echocardiographic views were obtained more consistently with 2-D ultrasound than with 3-D volume data.

Echocardiography, Doppler↗

PubMed2000

Hypereosinophilia induced by high-dose intratumoral and peritumoral mistletoe application to a patient with pancreatic carcinoma.

UNLABELLED: A patient with inoperable adenocarcinoma of the pancreas was treated with intraperitumoral and peritumoral injections of a Viscum album L. extract containing 5,700 ng/mL mistletoe lectin, mainly mistletoe lectin 1 (Abnobaviscum Quercus 2) for 5 weeks (1 injection per week). After the third injection (day 22), a marked eosinophilia was observed (1,800 per microliter) that rose to 3,268 per microliter after the fifth injection (day 42). Furthermore, histology performed on day 28 revealed accumulation of eosinophils in ductal lesions and adjacent stroma in addition to the features of ductal adenocarcinoma. In order to investigate whether eosinophilia correlated with immunological features, we analyzed cytokine production of peripheral blood mononuclear cells (PBMC) from this patient after stimulation with antigens known to "unmask" an individual's predisposition for defined immunoreactions, namely purified protein derivative (PPD) as a stimulator of T-helper (TH1)1-cells and tetanus toxoid (TT) as an activator of TH2-cells. PBMC of the patient showed a strong proliferation and production of interleukin (IL)-5 and IL-10 after incubation with TT indicating a type-2 response. Simultaneously, PBMC were induced to proliferate and produce interferon gamma (IFN-gamma) by incubation with PPD suggesting also a type-1 response. These data would readily explain the eosinophilia because eosinophils are effector cells of type-2 reaction but also require type-1 cytokines. Although the overall clinical course of the patient was rapidly progressive, temporary stabilization of the patient's general condition during mistletoe treatment was observed. It is, however, still an open question whether this transient benefit was due to the induction of eosinophilia by a type-2 response. CONCLUSION: Before high-dose intratumoral and peritumoral treatment with a Viscum album L. extract containing mistletoe, lectin 1 can be associated with hypereosinophilia and strong production of TH1 as TH2 cytokines as well.

Adenocarcinoma↗

PubMed2000

The C terminus of component C2II of Clostridium botulinum C2 toxin is essential for receptor binding.

The binary Clostridium botulinum C2 toxin consists of two separate proteins, the binding component C2II (80.5 kDa) and the actin-ADP-ribosylating enzyme component C2I (49.4 kDa). For its cytotoxic action, C2II binds to a cell membrane receptor and induces cell entry of C2I via receptor-mediated endocytosis. Here we studied the structure-function relationship of C2II by constructing truncated C2II proteins and producing polyclonal antisera against selective regions of C2II. An antibody raised against the C terminus (amino acids 592 to 721) of C2II inhibited binding of C2II to cells. The antibody prevented pore formation by C2II oligomers in artificial membranes but did not influence the properties of existing channels. To further define the region responsible for receptor binding, we constructed proteins with deletions in C2II; specifically, they lacked amino acid residues 592 to 721 and the 7 C-terminal amino acid residues. The truncated proteins still formed sodium dodecyl sulfate-stable oligomers but were unable to bind to cells. Our data indicate that the C terminus of C2II mediates binding of the protein to cells and that the 7 C-terminal amino acids are structurally important for receptor binding.

Binding Sites↗

PubMed2000

Regulated von Willebrand factor secretion is associated with agonist-specific patterns of cytoskeletal remodeling in cultured endothelial cells.

von Willebrand factor (vWF), an adhesive glycoprotein involved in primary hemostasis, is stored and released from endothelial secretory granules called Weibel-Palade bodies. Regulated secretion occurs in reaction either to [Ca(2+)](i)-raising agents (histamine or thrombin) or to cAMP-raising agents (epinephrine, adenosine, or forskolin). We investigated the pattern of release and the cytoskeletal requirements for secretion in response to these 2 classes of agonists. Secretion induced by [Ca(2+)](i)-raising agents involves peripheral and central granules and is inhibited by colchicine-induced microtubule disruption. It is accompanied by Rho-dependent stress fiber formation and cell retraction. Secretion and remodeling occur in the same individual cells. However, secretion is potentiated by cytochalasin E and C3 toxin, indicating that stress fiber formation antagonizes vWF secretion. In contrast, vWF secretion induced by cAMP-raising agents involves the release of only peripheral granules (implying less vWF release on a per cell basis) and is not inhibited by microtubule disruption. cAMP-mediated secretion is accompanied by disruption of stress fibers, strengthening of the cortical actin rim, and preservation of cell-cell contacts. It is unaffected by cytochalasins or C3 toxin. In contrast to [Ca(2+)](i)-raising agents, cAMP-raising agents induce secretion without cell retraction/intercellular gap formation. Thus, they are likely to play a physiological role in the regulation of endothelial vWF secretion and, therefore, of plasma vWF levels.

ADP Ribose Transferases↗

PubMed1999

Neosynthesis and activation of Rho by Escherichia coli cytotoxic necrotizing factor (CNF1) reverse cytopathic effects of ADP-ribosylated Rho.

Clostridium botulinum exoenzyme C3 inactivates the small GTPase Rho by ADP-ribosylation. We used a C3 fusion toxin (C2IN-C3) with high cell accessibility to study the kinetics of Rho inactivation by ADP-ribosylation. In primary cultures of rat astroglial cells and Chinese hamster ovary cells, C2IN-C3 induced the complete ADP-ribosylation of RhoA and concomitantly the disassembly of stress fibers within 3 h. Removal of C2IN-C3 from the medium caused the recovery of stress fibers and normal cell morphology within 4 h. The regeneration was preceded by the appearance of non-ADP-ribosylated RhoA. Recovery of cell morphology was blocked by the proteasome inhibitor lactacystin and by the translation inhibitors cycloheximide and puromycin, indicating that intracellular degradation of the C3 fusion toxin and the neosynthesis of Rho were required for reversal of cell morphology. Escherichia coli cytotoxic necrotizing factor CNF1, which activates Rho by deamidation of Gln(63), caused reconstitution of stress fibers and cell morphology in C2IN-C3-treated cells within 30-60 min. The effect of CNF1 was independent of RhoA neosynthesis and occurred in the presence of completely ADP-ribosylated RhoA. The data show three novel findings; 1) the cytopathic effects of ADP-ribosylation of Rho are rapidly reversed by neosynthesis of Rho, 2) CNF1-induced deamidation activates ADP-ribosylated Rho, and 3) inhibition of Rho activation but not inhibition of Rho-effector interaction is a major mechanism underlying inhibition of cellular functions of Rho by ADP-ribosylation.

Adenosine Diphosphate Ribose↗

PubMed1999

Role of Rho and Rho kinase in the activation of volume-regulated anion channels in bovine endothelial cells.

1. We have studied the modulation of volume-regulated anion channels (VRACs) by the small GTPase Rho and by one of its targets, Rho kinase, in calf pulmonary artery endothelial (CPAE) cells. 2. RT-PCR and immunoblot analysis showed that both RhoA and Rho kinase are expressed in CPAE cells. 3. ICl,swell, the chloride current through VRACs, was activated by challenging CPAE cells with a 25 % hypotonic extracellular solution (HTS) or by intracellular perfusion with a pipette solution containing 100 microM GTPgammaS. 4. Pretreatment of CPAE cells with the Clostridium C2IN-C3 fusion toxin, which inactivates Rho by ADP ribosylation, significantly impaired the activation of ICl,swell in response to the HTS. The current density at +100 mV was 49 +/- 13 pA pF-1 (n = 17) in pretreated cells compared with 172 +/- 17 pA pF-1 (n = 21) in control cells. 5. The volume-independent activation of ICl,swell by intracellular perfusion with GTPgammaS was also impaired in C2IN-C3-pretreated cells (31 +/- 7 pA pF-1, n = 11) compared with non-treated cells (132 +/- 21 pA pF-1, n = 15). 6. Activation of ICl,swell was pertussis toxin (PTX) insensitive. 7. Y-27632, a blocker of Rho kinase, inhibited ICl,swell and delayed its activation. 8. Inhibition of Rho and of Rho kinase by the above-described treatments did not affect the extent of cell swelling in response to HTS. 9. These experiments provide strong evidence that the Rho-Rho kinase pathway is involved in the VRAC activation cascade.

Amides↗

PubMed1999

Immune regulatory loops determine productive interactions within human T lymphocyte-dendritic cell clusters.

Help for the induction of cytolytic T lymphocytes is mediated by dendritic cells (DC) that are conditioned by CD40 signaling. We identified tumor necrosis factor family member CD27L/CD70, which is expressed by cytolytic T lymphocytes on interaction with DC to control CD154 (CD40L) up-regulation on CD45RA+ helper T cells for subsequent DC stimulation. The results show that the initiation of a cytolytic immune response is determined by regulatory circuits, requiring simultaneous activation and differentiation of all cells involved in T lymphocyte-DC cluster formation.

Animals↗

PubMed1999

Is there any relationship between eosinophilia myalgia syndrome (EMS) and fibromyalgia syndrome (FMS)? An analysis of clinical and immunological data.

The eosinophilia-myalgia syndrome (EMS) caused by intake of contaminated L-tryptophan resembles in its clinical presentation the fibromyalgia syndrome (FMS). We, therefore, analysed clinical and immunological parameters in 16 patients with chronic EMS and 100 patients with FMS in order to see whether there may be a relationship between both disorders. From 12 FMS patients and 12 controls also peripheral blood mononuclear cells (PBMC) were obtained. Myalgia and arthralgia was observed in chronic EMS in the same incidence as in patients with FMS (81%). Also antibodies to serotonin, gangliosides and phospholipids were present in both groups. In vitro stimulation of PBMC with different L-tryptophan preparations revealed in six of the 12 FMS patients but only two of the control individuals a production of type 2 cytokines (IL-5, IL-10). We, therefore, conclude that EMS may have developed in patients suffering primarily from FMS as an allergic reaction towards a more immunogenic L-tryptophan preparation.

Adult↗

PubMed1999

Thrombolysis with saruplase versus streptokinase in acute myocardial infarction: five-year results of the PRIMI trial.

BACKGROUND: Short-term safety and efficacy of thrombolysis with saruplase in acute myocardial infarction have been shown in several trials. To assess long-term outcome of patients treated with saruplase or streptokinase for myocardial infarction, a 5-year follow-up of patients included in the Pro-Urokinase in Myocardial Infarction Trial was performed. METHODS AND RESULTS: Follow-up data are available from 8 centers on 255 (92.4%) of 276 included patients. The 5-year mortality rate was comparable with 20.8% of patients in the saruplase group and 16.9% in the streptokinase group (odds ratio 1.29, 95% confidence interval 0.69 to 2.42). In both groups, a considerable number of fatal cardiovascular events occurred more than 1 year after study inclusion. Rates of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting were comparable in both groups. Reinfarction within 5 years occurred in 19.0% of patients in the saruplase group and tended to be less frequent at 10.8% after streptokinase treatment (odds ratio 1.94, 95% confidence interval 0.98 to 3.84). In both groups, the majority of reinfarctions took place more than 3 months after study inclusion. The 5-year stroke rate was 3.6% and 7.2% in the saruplase and streptokinase groups, respectively (odds ratio 0.49, 95% confidence interval 0.16 to 1.47). Subjective symptoms of heart failure and angina pectoris were comparable in both groups. CONCLUSIONS: Our data are consistent with a similar long-term outcome for patients treated with saruplase or streptokinase. Despite the low-risk profile of the patient cohort, there were considerable adverse event rates over a 5-year period.

Aged↗

PubMed1999

Saruplase is a safe and effective thrombolytic agent; observations in 1,698 patients: results of the PASS study. Practical Applications of Saruplase Study.

Saruplase (unglycosylated human-type high molecular weight single-chain urokinase-type plasminogen activator) was given to 1698 patients in the open-label Practical Applicability of Saruplase Study (PASS), which assessed the safety and efficacy of saruplase in the treatment of acute myocardial infarction. Thirty-seven hospitals in Europe participated in the study. All patients received 20 mg saruplase as a bolus followed by an infusion of 60 mg saruplase over 1 hour. Prior to the infusion of saruplase, 62% of the patients received a bolus of 5000 U of heparin, and after saruplase a 24-hour intravenous infusion of heparin was given to 95% of patients. The mean age of the patients was 59 years and 80.1% were male. The median delay from the onset of chest pain to the start of saruplase infusion was 145 minutes. Acute angiography was performed in 8 of the participating 37 centers in 350 patients (20.6%), on average 85 minutes (median) after the start of the saruplase infusion. TIMI 3 flow was obtained in 186 patients (53.1%) and TIMI 2 flow in 61 patients (17.4%). Patency rates were similar for patients with anterior and inferior infarction. ECG signs suggestive of reperfusion were seen in 63% of the patients. In-hospital mortality was low (92 patients; 5.4%), and nonfatal recurrent myocardial infarction was seen in 60 patients (3.5%). Severe bleeding complications occurred in 92 patients (5.4%), 21 of whom (1.2%) needed a blood transfusion. An intracerebral hemorrhage was observed in eight patients (0.5%), and seven patients (0.4%) suffered from a thromboembolic stroke. At discharge 85.9% of the patients were in NYHA functional class I. One-year mortality was low (142 patients; 8. 4%). Mortality was high in patients with TIMI 0 or 1 flow at the acute angiography who did not undergo rescue PTCA (9/39; 23.1%), lower in patients with TIMI 0 or 1 flow followed by successful rescue PTCA (7/64; 10.9%), and low in patients with TIMI 2 flow (1/61; 1.6%) or with TIMI 3 flow (2/186; 1.1%). Patency rates and (bleeding) complications did not differ between patients with a body weight greater than or less than 70 kilograms. No antibodies against saruplase were detected in samples from 455 patients. In conclusion, it can be stated that saruplase, given in combination with aspirin and intravenous heparin, can be given safely and effectively to patients with acute myocardial infarction.

Aged↗

PubMed1999

Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cells.

The Clostridium botulinum C2 toxin ADP-ribosylates monomeric actin, thereby inducing disassembly of actin filaments, alteration of focal adhesions, and rounding of cells. After treatment with C2 toxin, cells stop to proliferate but remain viable for about 2 days. In view of reported correlations between the structure of the actin cytoskeleton and cell cycle transition, the effects of C2 toxin on the G(2)/M phase transition of the cell division cycle were studied. Since C2 toxin delayed entry into mitosis in HeLa cells, those enzymes which control entry into mitosis, the cyclin-dependent protein kinase mitosis-promoting factor (MPF) and the phosphatase cdc25-C were examined after treatment of synchronized cells with C2 toxin. MPF is composed of the regulatory cyclin B and the enzymatic p34cdc2 kinase subunits. For its activation at the G2/M border, p34cdc2 needs to be associated with cyclin B and additionally dephosphorylated at Tyr-15 by the specific phosphatase cdc25-C. Treatment of synchronized cells in S or G2 phase with C. botulinum C2 toxin prevented p34cdc2 protein kinase activation by inhibiting its tyrosine dephosphorylation at the G2/M border. Furthermore, the activity of cdc25-C phosphatase was decreased after treatment of cells with C2 toxin. Our results suggest that the prevented activation of the mitotic inducers p34cdc2 kinase and cdc25-C phosphatase represents the final downstream events in the action of C2 toxin resulting in a G(2) phase cell cycle delay in synchronized HeLa cells.

Botulinum Toxins↗

PubMed1998

Characterization of the catalytic site of the ADP-ribosyltransferase Clostridium botulinum C2 toxin by site-directed mutagenesis.

The actin ADP-ribosylating Clostridium botulinum C2 toxin is a binary toxin composed of the binding component C2II and the enzyme component C2I. C2I ADP-ribosylates G-actin at arginine 177, resulting in the depolymerization of the actin cytoskeleton. Here, we studied the structure-function relationship of C2I by site-directed mutagenesis. Exchange of Glu389 to glutamine caused the complete loss of ADP-ribosyltransferase and NAD-glycohydrolase activities of C2I. In contrast, exchange of Glu387 to glutamine blocked ADP-ribosyltransferase but not NAD-glycohydrolase activity. Whereas photoaffinity labeling of the double mutant E387Q/E389Q C2I with [carbonyl-14C]NAD was blocked, labeling of the single C2I mutants was reduced (E389Q) or not changed (E387Q). Exchange of the STS motif (amino acid residues 348-350) of C2I caused a decrease in transferase activity by more than 99 (S348A) and 90% (T349V), or did not affect activity (S350A). Exchange of Arg299 and Arg300 to lysine reduced transferase activity to <0.1 and approximately 35% of wild-type activity. The data indicate that the amino acid residues Glu389, Glu387, Ser348, and Arg299, which are conserved in various prokaryotic and eukaryotic arginine-modifying ADP-ribosyltransferases, are essential for ADP-ribosyltransferase activity of the enzyme component of C. botulinum C2 toxin.

Amino Acid Sequence↗

PubMed1998

Randomized, double-blind study comparing saruplase with streptokinase therapy in acute myocardial infarction: the COMPASS Equivalence Trial. Comparison Trial of Saruplase and Streptokinase (COMASS) Investigators.

OBJECTIVES: This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. BACKGROUND: The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. METHODS: Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for < 6 h entered the study at a total of 104 centers and were randomized to receive streptokinase (1.5-MU infusion over 60 min) or saruplase (20-mg bolus and 60-mg infusion over 60 min). In the saruplase group, a bolus of heparin (5,000 IU) was administered before saruplase, and a corresponding blinded double-dummy placebo bolus was administered before streptokinase. All patients received intravenous heparin infusions for > or = 24 h starting 30 min after the end of the thrombolytic infusions; the infusions were titrated to maintain an activated partial thromboplastin time at 1.5 to 2.5 times that of normal. RESULTS: Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p < 0.01 for equivalence). Hemorrhagic strokes occurred more often in patients receiving saruplase (0.9% vs. 0.3%), whereas thromboembolic strokes were more prevalent in the streptokinase-treated patients (0.5% vs. 1.0%). The rate of bleeding was similar in the two treatment groups (10.4% vs. 10.9%). Hypotension and cardiogenic shock occurred less frequently in the saruplase group. Reinfarction rates were similar. CONCLUSIONS: Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.

Aged↗

PubMed1998

Influence of Clostridium botulinum C2 toxin on Fc epsilonRI-mediated secretion and tyrosine phosphorylation in RBL cells.

We studied the effects of the binary Clostridium botulinum C2 toxin on stimulated [3H]serotonin release and protein tyrosine phosphorylation in RBL 2H3 hm1 cells. Actin was specifically ADP-ribosylated by C2 toxin in intact cells resulting in a 2-3 fold increase in antigen- or calcium ionophore (A23187)-induced degranulation. The effects of C2 toxin were time- and concentration-dependent. Toxin treatment, which dramatically changes the morphology of RBL cells, was not sufficient to induce mediator release in the absence of activators of secretion. Antigen- and A23187-stimulated tyrosine phosphorylation of 60-80 kDa and 110-120 kDa proteins was reduced or blocked after C2 toxin incubation. Treatment of RBL cells with the tyrosine phosphatase inhibitor pervanadate reversed the inhibitory effect of C2 toxin on stimulated protein tyrosine phosphorylation indicating activation of phosphatases by C2 toxin. The data indicate that disassembly of the actin cytoskeleton by C2 toxin facilitates Fc epsilonRI-mediated signal-secretion coupling and suggest a role of the actin cytoskeleton in phosphatase regulation in RBL cells.

Actins↗

PubMed1998

Spinal drop metastases in recurrent glioblastoma multiforme.

Multifocal dissemination of glioblastomas is very rare but is increasing as patients live longer. Between April 1994 and December 1997 one hundred and fifty one patients with a histologically proven glioblastoma multiforme were operated on in the Neurosurgical Department of the University of Kiel, Germany. Recurrent tumours of these patients were removed in 36 patients. Two patients developed multifocal spread of glioblastoma multiforme including spinal drop metastases. Both patients died 10 and 7 months after the primary operation. On histological examination both tumours showed wide perivascular tumour-cell cuffings in the surrounding brain tissue, so that this perivascular growth might be another explanation for the dissemination in these glioblastomas.

Brain↗