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Biomedical subjects

M Naumann

Publications and source records attributed to M Naumann.

At least 73 records · Page 4Linked to original sources
PubMed2000

Generation of catalytically active 6-phosphofructokinase from Saccharomyces cerevisiae in a cell-free system.

PFK1 and PFK2 coding for the subunits of 6-phosphofructokinase from Saccharomyces cerevisiae were cloned into plasmids suitable for runoff transcription. In vitro translation products of both kinds of subunit were obtained using rabbit reticulocyte lysate as the synthesis and folding system. They were monitored by chemiluminescent Western-blot analysis. Folding and assembly of the alpha-subunit and beta-subunit of 6-phosphofructokinase were found to occur in the cell-free system resulting in an enzymatically active protein. The in vitro generated enzyme exhibits a folding state that is similar to that of the heterooctameric form of 6-phosphofructokinase in the presence of fructose 6-phosphate, ATP and ammonium sulfate, as demonstrated by size-exclusion HPLC followed by ELISA.

Adenosine Triphosphate↗
PubMed2000

Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus.

Helicobacter pylori is one of the most common bacterial pathogens, infecting about 50% of the world population. The presence of a pathogenicity island (PAI) in H. pylori has been associated with gastric disease. We present evidence that the H. pylori protein encoded by the cytotoxin-associated gene A (cagA) is translocated and phosphorylated in infected epithelial cells. Two-dimensional gel electrophoresis (2-DE) of proteins isolated from infected AGS cells revealed H. pylori strain-specific and time-dependent tyrosine phosphorylation and dephosphorylation of several 125-135 kDa and 75-80 kDa proteins. Immunoblotting studies, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), cell fractionation and confocal microscopy demonstrated that one of the 125-135 kDa proteins represents the H. pylori CagA protein, which is translocated into the host cell membrane and the cytoplasm. Translocation of CagA was dependent on functional cagA gene and virulence (vir) genes of a type IV secretion apparatus composed of virB4, virB7, virB10, virB11 and virD4 encoded in the cag PAI of H. pylori. Our findings support the view that H. pylori actively translocates virulence determinants, including CagA, which could be involved in the development of a variety of gastric disease.

Adenocarcinoma↗
PubMed2000

Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis.

Sialorrhoea is a socially disabling problem in bulbar amyotrophic lateral sclerosis (ALS). Botulinum toxin A (BoNT/A) was injected into the salivary glands in five patients with bulbar ALS and sialorrhoea. The effect of BoNT/A was measured by the number of paper handkerchiefs used each day and by salivary gland scintigraphy. BoNT/A ameliorated sialorrhoea and quality of life without major adverse effects. BoNT/A may be a relatively safe and effective treatment for sialorrhoea in selected patients.

Aged↗
PubMed2000

Cerebral activation pattern in primary writing tremor.

OBJECTIVE: To compare the cerebral activation pattern during writing of patients with writing tremor with healthy controls using functional MRI METHODS: Three patients with writing tremor and 10 healthy controls were examined using a 1.5 Tesla scanner. All subjects performed a paradigm of alternating 30 second periods of rest or writing. For functional imaging 60 EPI multislice data sets were acquired. All images were analyzed using SPM96 software. Data were analyzed for the group of patients with writing tremor and compared with those of the control group. RESULTS: Both patients with writing tremor and controls showed a significant activation of the contralateral primary sensorimotor cortex, SMA, and area 44. By contrast, motor cortex activation in writing tremor also included the contralateral premotor area (area 6) and ipsilateral prefrontal area (inferior frontal gyrus; areas 10, 44, and 47). Only patients with writing tremor showed a bilateral activation of the parietal lobule (area 40) with a more pronounced activation on the contralateral side. Furthermore, there was a bilateral activation of the cerebellum with a more pronounced area of activation on the ipsilateral side. CONCLUSIONS: Brain areas activated in writing tremor included activation patterns otherwise typical for both essential tremor and writer's cramp. Therefore a distinct category for writing tremor integrating hallmarks of essential tremor and writer's cramp is proposed.

Adult↗
PubMed2000

Sensory tricks in cervical dystonia: perceptual dysbalance of parietal cortex modulates frontal motor programming.

Cervical dystonia is a disabling basal ganglia disorder characterized by an involuntary head deviation to one side. A typical but also mysterious feature is the impressive improvement of muscle spasms and involuntary head posture by application of a sensory facial stimulus (sensory trick). Here, we report the effect of a sensory trick on cortical activation patterns in 7 patients with cervical dystonia by using H2(15)O positron emission tomography. The application of the sensory trick stimulus, resulting in a near-neutral head position, led to an increased activation mainly of the superior and inferior parietal lobule (ipsilateral to the original head turn) and bilateral occipital cortex and to a decreased activity of the supplementary motor area and the primary sensorimotor cortex (contralateral to the head turn). We propose that a perceptual dysbalance induced by a sensory trick maneuver leads to a relative displacement of the egocentric midvertical reference to the opposite side and a decrease in motor cortex activity. This modulation of motor programming gives novel insights into the mechanisms involved in sensorimotor integration in movement disorders.

Adult↗
PubMed2000

Changes of copper-transporting proteins and ceruloplasmin in the lentiform nuclei in primary adult-onset dystonia.

A recent study reported an increase of brain tissue copper content in the lentiform nuclei of patients with primary adult-onset dystonia. In this study we analyze copper-metabolizing proteins (Menkes protein, Wilson protein, ceruloplasmin) by Western blot analysis in frozen brain tissue (lentiform nuclei) of 3 patients with primary dystonia. Menkes protein was reduced in all patients, while Wilson protein and ceruloplasmin were increased in the 2 patients with focal dystonia and reduced in the patient with generalized dystonia. Our data provides further evidence for a disturbance of copper metabolism in primary dystonia.

Adenosine Triphosphatases↗
PubMed1999

COP9 signalosome-directed c-Jun activation/stabilization is independent of JNK.

The basic region-leucine zipper transcription factor c-Jun regulates gene expression and cell function. It participates in the formation of homo- or heterodimeric complexes that specifically bind to DNA sequences called activating protein 1 (AP-1) sites. The stability and activity of c-Jun is regulated by phosphorylation within the N-terminal activation domain. Mitogen- and stress-activated c-Jun N-terminal kinases (JNKs) were previously the only described enzymes phosphorylating c-Jun at the N terminus in vivo. In this report we demonstrate a JNK-independent activation of c-Jun in vivo directed by the constitutive photomorphogenesis (COP9) signalosome. The overexpression of signalosome subunit 2 (Sgn2), a subunit of the COP9 signalosome, leads to de novo assembly of the complex with a partial incorporation of the overexpressed subunit. The de novo formation of COP9 signalosome parallels an increase of c-Jun protein resulting in elevated AP-1 transcriptional activity. The c-Jun activation caused by Sgn2 overexpression is independent of JNK and mitogen-activated protein kinase kinase 4. The data demonstrate the existence of a novel COP9 signalosome-directed c-Jun activation pathway.

COP9 Signalosome Complex↗
PubMed1999

Activation of activator protein 1 and stress response kinases in epithelial cells colonized by Helicobacter pylori encoding the cag pathogenicity island.

Helicobacter pylori interacts with the apical membrane of the gastric epithelium and induces a number of proinflammatory cytokines/chemokines. The subsequent infiltration of macrophages and granulocytes into the mucosa leads to gastric inflammation accompanied by epithelial degeneration. Gastric diseases, e.g. peptic ulcer or gastric adenocarcinoma, are more common among people infected with H. pylori strains producing VacA (vacuolating cytotoxin A) and possessing a cag (cytotoxin-associated antigen A) pathogenicity island. For the induction of the cytokine/chemokine genes in response to H. pylori, we studied the signaling leading to the nuclear activation of the early response transcription factor activator protein 1 (AP-1). We found that H. pylori strains carrying the pathogenicity island induce activation of AP-1 and nuclear factor kappaB. In contrast to the wild type or an isogenic strain without the vacA gene, isogenic H. pylori strains with mutations in certain cag genes revealed only weak AP-1 and nuclear factor kappaB activation. In respect to the molecular components that direct AP-1 activity, our results indicate a cascade of the cellular stress response kinases c-Jun N-terminal kinase, MAP kinase kinase 4, and p21-activated kinase, and small Rho-GTPases including Rac1 and Cdc42, which contributes to the activation of proinflammatory cytokines/chemokines induced by H. pylori encoding the cag pathogenicity island.

Antigens, Bacterial↗
PubMed1999

INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB.

The nuclear factor kappaB, a transcription factor regulating the expression of multiple genes including genes essential for cell cycle control, is found in most cells in a dormant state in the cytoplasm bound to the inhibitory family I kappaB via an ankyrin repeat domain. Stimulation of cells with a variety of inducers inactivates I kappaB proteins. The active dimeric NF-kappaB complex, often composed of 50- and 65-kilodalton subunits of the Rel family, translocates into the nucleus, where the NF-kappaBp65 subunit stimulates transcription. Here we report that a family of proteins containing ankyrin repeats, the inhibitors of Cdk4 (INK4) is able to bind NF-kappaBp65. The association of p16INK4 with NF-kappaBp65 is considerable in HeLa- or 293 cells, if the NF-kappaB inhibitor I kappaB alpha is degraded in response to TNFalpha stimulation. Overexpression of INK4 molecules suppresses the transactivational ability of NF-kappaB significantly. In contrast to INK4 proteins, the cell cycle inhibitor p27 enhances NF-kappaB transactivation activity. Thus, the effect of INK4 proteins on NF-kappaB function possibly modifies NF-kappaB mediated transcriptional activation of cell cycle associated factors.

Ankyrins↗
PubMed1999

Neisserial porin (PorB) causes rapid calcium influx in target cells and induces apoptosis by the activation of cysteine proteases.

The porin (PorB) of Neisseria gonorrhoeae is an intriguing bacterial factor owing to its ability to translocate from the outer bacterial membrane into host cell membranes where it modulates the infection process. Here we report on the induction of programmed cell death after prolonged infection of epithelial cells with pathogenic Neisseria species. The underlying mechanism we propose includes translocation of the porin, a transient increase in cytosolic Ca2+ and subsequent activation of the Ca2+ dependent protease calpain as well as proteases of the caspase family. Blocking the porin channel by ATP eliminates the Ca2+ signal and also abolishes its pro-apoptotic function. The neisserial porins share structural and functional homologies with the mitochondrial voltage-dependent anion channels (VDAC). The neisserial porin may be an analogue or precursor of the ancient permeability transition pore, the putative central regulator of apoptosis.

Adenosine Triphosphate↗
PubMed1999

GAG deletion in the DYT1 gene in early limb-onset idiopathic torsion dystonia in Germany.

We examined 57 patients with idiopathic torsion dystonia (ITD) for the 3-bp GAG deletion in the DYT1 gene on human chromosome 9q34. Three of five patients with early limb-onset ITD, one of them with a positive family history, tested positive for the mutation, as did one young patient with multifocal dystonia and a short course of the disease. Two patients with early-onset generalized dystonia beginning in the cervical muscles, as well as five other patients with multifocal, 14 patients with segmental, and 30 patients with focal cervical dystonia did not carry the mutation. This suggests that the GAG deletion is responsible for a major portion of cases of typical early limb-onset dystonia, but not for other types of dystonia, in our population.

Adolescent↗
PubMed1999

Successful treatment of crocodile tears by injection of botulinum toxin into the lacrimal gland: a case report.

OBJECTIVE: Pathologic lacrimation (crocodile tears) is a rare but stigmatizing symptom after facial nerve paralysis. The aim of this pilot study was to examine whether botulinum toxin injection into the lacrimal gland is effective in reducing pathologic tear secretion. DESIGN: Case report. INTERVENTION: One patient who had crocodile tears after a zoster oticus infection received a botulinum toxin injection (2.5 mouse units) into the lacrimal gland. TESTING: Before injection, 1 week, 1 month, and 6 months after injection, patient's lacrimation was assessed by a Schirmer test. RESULTS: The lacrimation of the injected eye was reduced after 1 week and equal after 1 month when compared to the healthy side. After 6 months, hyperlacrimation reoccurred. No side effects were observed. CONCLUSION: Intraglandular injection of botulinum toxin into the lacrimal gland may serve as a sufficient therapy for crocodile tears.

Botulinum Toxins, Type A↗
PubMed1999

Host cell interactions and signalling with Neisseria gonorrhoeae.

Neisseria gonorrhoeae is a highly adapted human pathogen that utilises multiple adhesins to interact with a variety of host cell receptors. Recently, substantial progress has been made in unravelling the signalling events induced by N. gonorrhoae that can lead to cytoskeletal reorganisation, invasion or phagocytic uptake, intraphagosomal accommodation, nuclear signalling, cytokine/chemokine release and apoptosis.

Animals↗