Biomedical subjects

C Mayer

Publications and source records attributed to C Mayer.

At least 109 records · Page 6Linked to original sources

PubMed1998

Activity-dependent intracellular Ca2+ transients in unmyelinated nerve fibres of the isolated adult rat vagus nerve.

Confocal laser scanning microscopy was used to follow changes in the free intracellular calcium concentration ([Ca2+]i) in nerve fibres and adjacent Schwann cells in isolated rat vagus nerves. [Ca2+]i was monitored by the Ca2+-sensitive fluorescent dyes Calcium Green-1 and Fura Red. Intracellular Ca2+ transients were observed during repetitive (1-50 Hz) supramaximal electrical stimulation or by bath application of ATP. Trains of action potentials were more effective at elongated, fibre-like structures of the vagus nerves, whereas ATP-induced Ca2+ transients were found predominantly in regions of Schwann cell bodies. Activity-induced Ca2+ signals were unaffected by pharmacological manipulation of intracellular Ca2+ stores, during long-lasting application of purinergic receptor agonists, or by substitution of extracellular Na+ with Li+. However, they were abolished in the presence of Ca2+-free bathing solution or after the blocking of Ca2+ channels with Cd2+. Ca2+ transients were also observed during Ca2+ action potentials. Such "Ca2+ spikes" were elicited by electrical stimulation in the presence of a combination of tetrodotoxin and K+ channel blockers. These data suggest that voltage-dependent Ca2+ channels, activated during short trains of Na+ action potentials, produce an increase in intra-axonal [Ca2+] of rat vagus nerves. We did not find evidence for activity-dependent Ca2+ transients in the Schwann cells surrounding the unmyelinated axons.

Action Potentials↗

PubMed1998

MK-886, a leukotriene biosynthesis inhibitor, induces antiproliferative effects and apoptosis in HL-60 cells.

MK-886, a specific inhibitor of 5-lipoxygenase inhibited DNA replication in leukemic HL-60 cells in a dose-dependent manner. Addition of exogenous leukotriene B4 reversed this effect, whereas addition of leukotriene B4 failed to modulate a prostaglandin D2-induced inhibition of DNA replication. The reversal of MK-886-induced inhibition was not observed with leukotriene C4. These results suggest that the effect of MK-886 is mediated by inhibition of leukotriene B4 biosynthesis. Moreover, MK-886 not only impaired DNA replication in HL-60 cells but also decreased cell proliferation and induced apoptotic cell death. Our results suggest a crucial role of leukotriene B4 in the regulation of cell proliferation and cell survival in HL-60 cells.

Apoptosis↗

PubMed1998

MvaL1 autoregulates the synthesis of the three ribosomal proteins encoded on the MvaL1 operon of the archaeon Methanococcus vannielii by inhibiting its own translation before or at the formation of the first peptide bond.

The control of ribosomal protein synthesis has been investigated extensively in Eukarya and Bacteria. In Archaea, only the regulation of the MvaL1 operon (encoding ribosomal proteins MvaL1, MvaL10 and MvaL12) of Methanococcus vannielii has been studied in some detail. As in Escherichia coil, regulation takes place at the level of translation. MvaL1, the homologue of the regulatory protein L1 encoded by the L11 operon of E. coli, was shown to be an autoregulator of the MvaL1 operon. The regulatory MvaL1 binding site on the mRNA is located about 30 nucleotides downstream of the ATG start codon, a sequence that is not in direct contact with the initiating ribosome. Here, we demonstrate that autoregulation of MvaL1 occurs at or before the formation of the first peptide bond of MvaL1. Specific interaction of purified MvaL1 with both 23S RNA and its own mRNA is confirmed by filter binding studies. In vivo expression experiments reveal that translation of the distal MvaL10 and MvaL12 cistrons is coupled to that of the MvaL1 cistron. A mRNA secondary structure resembling a canonical L10 binding site and preliminary in vitro regulation experiments had suggested a co-regulatory function of MvaL10, the homologue of the regulatory protein L10 of the beta-operon of E. coil. However, we show that MvaL10 does not have a regulatory function.

Archaeal Proteins↗

PubMed1998

The radioprotective effect of BBI is associated with the activation of DNA repair-relevant genes.

PURPOSE: To investigate the molecular mechanisms of the radioprotective effect of the Bowman-Birk proteinase inhibitor (BBI) in normal human skin fibroblasts (HSF). MATERIAL AND METHODS: The effect of BBI pre-treatment on p53 protein level and on mRNA levels of downstream genes (ERCC3, Gadd45 and p53) was investigated. RESULTS: As indicated by time-course experiments based on clonogenic assays, a 6 h pre-incubation with BBI before irradiation of HSF with a single dose of 6 Gy resulted in maximum radioprotection. In non-irradiated cells, pre-incubation with BBI resulted in an increased level of p53 protein. Concomitantly, enhanced mRNA levels of the ERCC3 and the Gadd45 genes were observed. As a consequence, BBI-treated cells showed accelerated DNA repair compared with untreated cells when irradiated. CONCLUSIONS: The radioprotective effect of the Bowman-Birk proteinase inhibitor was accompanied by elevated mRNA expression of repair-relevant genes prior to irradiation. Activation of the DNA-repair machinery induced by pre-treatment with BBI is one possible mechanism of the radioprotective effect of BBI.

DNA Repair↗

PubMed1998

Bowman-Birk protease inhibitor reduces the radiation-induced activation of the EGF receptor and induces tyrosine phosphatase activity.

PURPOSE: To investigate the molecular action of the radioprotective Bowman Birk protease inhibitor (BBI) on radiation-induced tyrosine kinase activity. MATERIALS AND METHODS: Radiation-induced activation of tyrosine kinases and phosphatases was measured in normal human skin fibroblasts by in vitro kinase assays after pre-incubation with BBI. RESULTS: Pre-incubation with BBI resulted in a time-dependent block of the radiation-induced activation of tyrosine kinases. Whilst radiation-induced pp60c-Src activity was not modulated due to BBI pre-treatment, activation of epidermal growth factor receptor (EGFR) was inhibited. Additionally, pre-incubation with BBI resulted in enhanced tyrosine specific phosphatase (PTP) activity. CONCLUSIONS: BBI might exert its radioprotective activity by stabilizing specific tyrosine-phosphatases that interfere with EGFR activation in response to radiation exposure.

Enzyme Induction↗

PubMed1998

Transjugular intrahepatic portosystemic shunt and cardiac arrhythmias.

The approach to the liver for a transjugular intrahepatic porto-systemic shunt (TIPS) is through the venous system. Because catheter and guidewire system traverses the heart, cardiac arrhythmias may be expected during the procedure. We have prospectively investigated the incidence of such dysrhythmias during TIPS implantation. Twelve consecutive patients, 4 women and 8 men aged 26 to 75 years (mean, 58 +/- 13 years), were studied. Before and on the day of TIPS implantation, a 24-hour Holter recording was performed. Transjugular intrahepatic portosystemic shunt implantation was performed under local anesthesia (lidocaine) and sedoanalgesia (midazolam and fentanyl). None of the patients had concomitant cardiac disease or electrolyte disturbances. In all patients except one, TIPS implantation was successful without any technical complications. A mean of 43 +/- 5.3 hours of Holter recording was performed before and after TIPS implantation. All recordings obtained during this control period were considered inconspicuous. The mean heart rate was significantly higher during the implantation procedure of 136 +/- 37 minutes' duration (83 +/- 20 beats per minute vs 70 +/- 19 beats per minute; p < 0.01). Nine of the 12 patients experienced episodes of nonsustained supraventricular tachycardias, and one patient had two sustained supraventricular tachycardias. Frequent episodes of nonsustained ventricular tachycardias developed in 75% of the patients. It seems clear that TIPS implantation is frequently associated with supraventricular and ventricular tachyarrhythmias even in patients with apparently good cardiac condition at the beginning of the procedure. Thus close cardiac monitoring with resuscitation equipment immediately available throughout the procedure is mandatory.

Adult↗

PubMed1998

[Molecular aspects and diagnostic value of fungal allergens].

Cloning, sequencing and production of highly pure recombinant allergens allows to produce perfectly standardised allergen preparations. The development of a new cloning system based on filamentous phage allowed the fast isolation and characterisation of allergens from the fungus Aspergillus fumigatus. The produced recombinant allergens were tested in serological and clinical studies as well as for their performance for routine assessments in the ImmunoCAP-system. Thereby, a perfect correlation between skin test results and serology was found showing the potential of recombinant allergens for the diagnosis of allergic diseases. Moreover, the characterisation of fungal allergens substantially contributes to our understanding of the molecular nature of proteins involved in the elicitation of allergic reactions. Apart from allergenic proteins with unknown biological function, fungal allergens can be subdivided into two classes: 1. Species-specific, secreted proteins and 2. cytoplasmic, even in phylogenetically distant organisms, well conserved proteins. These fungal allergens show extended sequence similarity, a high level of IgE cross-reactivity and in some cases also cross-reactivity with homologous human proteins indicating autoimmune reactions involved in fungal allergy.

Allergens↗

PubMed1998

Predictors of outcome in patients with implantable cardioverter defibrillators.

UNLABELLED: This study determined the impact of clinical characteristics on shock occurrence and survival in patients with implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: During a follow-up of 27 +/- 18 months, the actuarial incidence of appropriate shocks in 200 consecutive patients was 18, 36 and 72% at 1, 3, and 5 years, respectively. Coronary artery disease was the only significant predictor for shock occurrence (relative risk 1.32, p = 0.03). The actuarial incidence of total mortality was 10, 17 and 33% at 1, 3, and 5 years, respectively. The most powerful predictors for total mortality were: New York Heart Association functional class (NYHA) III (relative risk 4.8, p = 0.001) and a history of congestive cardiac failure (relative risk 3.6, p = 0.01). CONCLUSION: During long-term follow-up, the majority of patients receive appropriate shocks. No strong predictors for shock occurrence can be identified from the data analyzed. A history of congestive cardiac failure and the NYHA III are the most powerful predictors for total mortality. These clinical factors may provide valuable criteria to identify patients who will benefit from the implantation of ICD.

Arrhythmias, Cardiac↗

PubMed1998

[Conversion syndromes in neurology. A psychopathological and psychodynamic differentiation of conversion disorder, somatization disorder and factitious disorder].

Conversion syndromes are frequent among medically unexplained somatic symptoms in neurology. A careful differential diagnosis must be carried out in a psychiatric consultation service. In a prospective study lasting for over four years 169 patients with pseudoneurological signs of conversion were included. From a clinical point of view the following conversion syndromes were presented: astasia/abasia: 27.2%, paresis/plegia: 24.3%, aphonia: 1.8%, hyp-/anaesthesia: 21.9%, blindness: 5.3%, non-epileptic seizures: 19.5%. According to the diagnostic criteria of DSM-III-R three subgroups were differentiated: conversion disorder (n = 132), somatisation disorder (n = 28), factitious disorder (n = 9). Intermittent courses of illness were prevailing in conversion disorder, whereas chronic courses predominated in the other two subgroups. High rates of psychiatric comorbidity were typical signs of somatisation disorder. Frequent autodestructive motives (suicidality, deliberate and covert self-harm, chronic pain, high rate of operations) in illness behaviour had to be registered in somatisation and factitious disorder. Both subgroups were characterised by frequent traumatic events during early development. Important socio-economic aspects of illness behaviour above all in somatisation and factitious disorder were underlined. The results are discussed in terms of psychiatric differential diagnosis and psychiatric comorbidity, psychodynamic evaluation, illness behaviour and therapeutic options in a C/L-service.

Adult↗

PubMed1998

The presence of wild-type TP53 is necessary for the radioprotective effect of the Bowman-Birk proteinase inhibitor in normal fibroblasts.

In the present study we have demonstrated that the Bowman-Birk proteinase inhibitor (BBI) protected normal fibroblasts from a radiation-induced reduction in cell survival, whereas in transformed fibroblasts no radioprotective effect was observed. It was shown that BBI reduced the radiation-induced protein stabilization and DNA-binding activity of TP53 (formerly known as p53) in normal fibroblasts. In transformed fibroblasts, BBI failed to induce these effects. The analysis of the TP53 gene in transformed fibroblasts revealed a mutation in exon 5. As a consequence of this mutation, the expression of the TP53 downstream gene CDKN1A (p21/WAF1/Cip1) is blocked. Based on experiments using TP53 antisense oligonucleotides, the radioprotective effect of BBI could be correlated with the function of wild-type TP53. Thus BBI can be considered as a selective radioprotective agent for normal human fibroblasts.

Base Sequence↗

PubMed1997

Intracellular calcium transients mediated by P2 receptors in the paranodal Schwann cell region of myelinated rat spinal root axons.

Receptors for neuroligands in the paranodal Schwann cell region of a myelinated nerve fiber could have important functions. We have used confocal laser scanning microscopy in combination with Ca(2+)-sensitive fluorescent dyes to study the possible effects of purinergic agonists on the free intracellular calcium concentration ([Ca2+]i) in paranodes of isolated rat spinal roots. Application of ATP in concentrations of 100 and 300 microM resulted in a transient rise in [Ca2+]i in about 57% of the paranodal Schwann cell regions studied. UTP was equipotent to ATP whereas adenosine, beta,gamma-methylene ATP, and elevation of the extracellular K+ concentration by 10 mM had no effect on [Ca2+]i. These data indicate the presence of the P2Y2 (previously termed P2U) subtype of P2 receptors in the paranodal Schwann cell membrane of rat spinal root myelinated nerve fibers.

Adenosine Triphosphate↗

PubMed1997

Hypnosis and cancer: an annotated bibliography 1985-1995.

The purpose of this annotated bibliography is to provide the reader with resources to explore the relationship between hypnosis and cancer. Items are included only if they contain explicit reference to this relationship and describe it in some detail. This bibliography includes 91 items published in English from 1985 to 1995, inclusive. For the reader's convenience, the annotations are organized into three categories: general discussions; case reports or case studies; and experimental and nonexperimental group designs.

Humans↗

PubMed1997

Course of illness in phobic postural vertigo.

Forty-two patients with phobic postural vertigo took part in a neurological and psychiatric follow-up study. During the follow-up time of about 2.5 years the neurological diagnosis remained stable (41 of 42 patients). PPV can be assigned to various psychiatric categories according to DSM-III-R. Although an association of PPV with anxiety disorders is evident, not all patients present with symptoms of anxiety or panic during attacks of vertigo. However most patients develop a disabling "phobic-avoidance pattern" with recurrent attacks. Important psychosocial stressors can be identified at the onset of the condition. Motives of secondary gain have also to be taken into consideration. The course of illness varies depending on the neurological syndrome of vertigo, on the one hand, and concomitant psychopathological syndromes, on the other. Despite a considerable rate of improvement in vertigo complaints (79%), the group of patients with phobic postural vertigo as a whole presented with significant psychological problems at follow-up term (74%), requiring specific psychiatric and/or psychotherapeutic interventions. Dependent or avoidant personality, and hypochondria were prognostic of a more negative course of illness.

Adult↗

PubMed1996

Glucose availability alters ischaemia-induced changes in intracellular pH and calcium of isolated rat spinal roots.

Peripheral nerves in diabetic patients show an enhanced liability to ischaemic lesions. Using an in vitro model, we have now analysed the possible role of intracellular proton (pHi) and calcium concentrations ([Ca2+]i) for the pathophysiology of this phenomenon. Isolated rat spinal roots were preincubated for 3 to 6 h in either 5 or 25 mM of D-glucose before transient exposure to gaseous hypoxia or cyanide. Intracellular pH and Ca2+ concentrations were measured photometrically by means of the fluorescent dyes carboxy-SNARF-1 and a combination of Calcium Green-1 and Fura Red, respectively. The following observations were made. (a) The presence of 25 mM D-glucose resulted in stronger intracellular acidification and much slower post-hypoxic recovery of pHi as compared to 5 mM D-glucose. (b) Intracellular calcium increased during hypoxia and recovered quickly on reoxygenation. There were no statistically significant differences between the Ca2+ signals in either high or normal concentrations of D-glucose, although on average less rise was seen in high glucose. (c) Inhibition of glycolysis with iodoacetate reduced the acidification but amplified the rise in [Ca2+]i seen during transient hypoxia. These data suggest that hypoxia-induced nerve acidification rather than a rise in [Ca2+]i might contribute to ischaemic lesions found in diabetic neuropathy.

Animals↗

PubMed1996

P2 purinoceptor-mediated intracellular Ca2+ transients in human sural nerve.

Segments of biopsied human sural nerve were stained with the Ca(2+)-sensitive fluorescent dyes Calcium Green-1 and Fura Red. The emission ratio was used to follow changes in the intracellular free Ca2+ concentration ([Ca2+]i). Application of ATP and analogues in concentrations between 0.3 and 300 microM via the bathing solution resulted in a transient rise in [Ca2+]i. The rank order of agonist potency, 2-methylthioATP > ATP > UTP, and the failure of adenosine, alpha,beta-MeATP and beta,gamma-MeATP to evoke rises in [Ca2+]i indicate the presence of P2Y/U subtypes of purinoceptors in this preparation. ATP-induced Ca2+ transients in biopsied human nerve preparations might serve as a diagnostic tool in neuropathies.

Adenosine Triphosphate↗

PubMed1996

Stereochemical requirements of chitin synthase for ligand binding at the allosteric site for N-acetylglucosamine.

The substrate kinetics of chitin synthase (CS) were non-Michaelian, irrespective of the type of enzyme preparation studied (105-S chitosomal CS, and 16-S ex walls), even in the presence of saturating GlcNAc. An unexplained idiosyncrasy of this enzyme, which is likely to be responsible for this phenomenon, is evident from the striking non-linearity of product deposition with time at low substrate or low enzyme concentrations, particularly in the absence of GlcNac. The possibility can be excluded that this non-linearity is due to the formation of soluble by-products or intermediates in the form of chito-oligomers, as shown by HPLC/pulsed amperometric detection analysis. Additional evidence was sought for the tenet that CS is homotropically-heterotropically regulated, at least under steady-state reaction conditions. Substrate kinetic curves established from rate data for the linear reaction phase only were used for modelling. These could be reasonably well parameterised on the basis of the Monod mathematical model for co-operative ligand binding. Within a series of test compounds used to assess the stereochemical conditions of the allosteric site of CS for effector binding, N-acetylglucosaminono-1,5-lactone oxime excelled. Requirements for effector binding are as follows: (a) an aminoglucopyranose skeleton with the amino function acetylated, and (b) a single-bonded oxo-function present at C(1), which is preferentially a hydrogen bond donor, that may be equatorially spaced off, but must not be alpha-anomeric. The implications of these findings for chitin synthesis in vivo are discussed in terms of a mechanistically based fitness of CS to operate efficiently under vastly different combinations of substrate could be coordinately linked to the catabolism of chitin.

Acetylglucosamine↗

PubMed1996

Use of T7 RNA polymerase in an optimized Escherichia coli coupled in vitro transcription-translation system. Application in regulatory studies and expression of long transcription units.

An Escherichia coli coupled in vitro transcription-translation system has been modified to allow efficient expression of genes under the control of a T7 promoter. We describe both the characterization and use of two S30 crude extracts prepared from E. coli, namely S30 BL21(DE3) (containing endogenous T7 RNA polymerase) and S30 BL21 (supplemented with exogenous T7 RNA polymerase). Since transcription by the highly active T7 RNA polymerase is known to overload the translational machinery of E. coli, the ratio between mRNA and ribosomes has to be regulated in the coupled in vitro system. For this purpose, the level of mRNA is controlled by varying the amount of DNA template (S30 extract with endogenous T7 RNA polymerase) or by limited amounts of exogenously added T7 RNA polymerase. The coupled in vitro system described in this paper provides two especially useful applications. First, it is most suitable for studying the regulation of gene expression in vitro, second, it can be used to express DNA templates carrying up to 10 genes. We show that genes which are not well expressed in E. coli in vivo because of unfavourable codon usage or plasmid instability are synthesized efficiently in the coupled in vitro system.

Bacterial Proteins↗

PubMed1996

Can the linguistic interdependence theory support a bilingual-bicultural model of literacy education for deaf students?

Drawing on Cummins' (1989) linguistic interdependence model, proponents of bilingual-bicultural models of literacy education for deaf students claim that, if ASL is well established as the L1, then literacy in English (L2) can be achieved by means of reading and writing without exposure to English through either speech or English-based sign. In our opinion, this claim is based on a false analogy: the situation of the deaf learner of English literacy does not match the conditions assumed by the linguistic interdependence model. We draw on the work of Vygotsky and Halliday to develop a conceptualization of the processes involved in becoming literate, examining the particular and unique challenges that deaf students face as they strive to become members of the linguistic community of users of written English. We argue that becoming literate involves mastering three modes of lanuage use: 'social speech,' 'inner speech,' and written text. In some respects the educational context for deaf students is analogous to that of other bilingual learners; in some crucial aspects, it is very different.

Journal Article↗