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M Naumann

Publications and source records attributed to M Naumann.

At least 91 records · Page 5Linked to original sources
PubMed1999

Comparison of human COP9 signalsome and 26S proteasome lid'.

The human core COP9 signalosome consists of eight subunits which have been identified, cloned and sequenced. The components of COP9 signalosome possess homologies with eight non-ATPase regulatory subunits of the 26S proteasome. These polypeptides of the 19S regulator form a reversibly binding subcomplex called the 'lid'. We isolated the 'lid' from human red blood cells and compared it with the COP9 signalosome complex. In addition to the non-ATPase regulatory polypeptides, we found a high molecular mass ATPase copurifying with the human 'lid'. The COP9 signalosome-associated kinase activity is either not at all or only weakly affected by common kinase inhibitors such as 1-(5-Isoquinolinesulfonyl)-2-methyl-piperazine (H7), 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB) or Wortmannin. Curcumin, a tumor suppressor and effector of AP-1 activation, is a potent inhibitor of the COP9 signalosome kinase activity with a Ki of about 10 microM. Since curcumin is known as an inhibitor of the c-Jun N-terminal kinase (JNK) signaling pathway acting upstream of the MAP kinase kinase kinase level, one site of action of the COP9 signalosome might be proximal to regulators on that level.

Animals↗
PubMed1999

[MRI in funicular myelosis].

The MRI morphology in combined subacute degeneration has only rarely been reported. We describe two patients suffering from subacute combined degeneration of the spinal cord on the basis of a deficiency of vitamin B12. In both patients characteristic hyperintense areas on T2-weighted images in the posterior columns of the cervical and thoracic cord without contrast enhancement were demonstrated by MRI.

Demyelinating Diseases↗
PubMed1999

TGFbeta-induced growth inhibition involves cell cycle inhibitor p21 and pRb independent from p15 expression.

It is generally assumed that TGFbeta induces cell cycle arrest through the cooperative action of cell cycle inhibitors p15, p27 and p21. Here, we found that several pancreatic carcinoma cell lines exert TGFbeta-induced negative growth control in spite of the loss of p15 and p16 expression. In these cell lines, TGFbeta-induced growth control correlates with the upregulation of the p21 protein and active pRb expression. Conversely, cells without p21 and/or pRb expression are resistant to TGFbeta -induced growth inhibition. Moreover, overexpression of p21 in the p21-deficient cell line Panc Tu1 leads to growth arrest. Thus, TGFbeta-induced growth control correlates with p21 expression and pRb status independent of p15 and/or p16 expression.

Cell Cycle Proteins↗
PubMed1998

Coordinate activation of activator protein 1 and inflammatory cytokines in response to Neisseria gonorrhoeae epithelial cell contact involves stress response kinases.

Neisseria gonorrhoeae (Ngo), the etiologic agent of gonorrhea, induce a number of proinflammatory cytokines by contact to epithelial cells. Cytokine genes and a variety of other immune response genes are activated as a result of the regulatory function of immediate early response transcription factors including activator protein 1 (AP-1). Since it is established that phosphorylation of c-Jun, the central component of AP-1, by the stress-activated c-Jun NH2-terminal kinase (JNK) increases the transcriptional activity of AP-1, we studied whether Ngo could induce stress response pathways involving JNK. We found that virulent Ngo strains induce phosphorylation and activation of JNK but not of p38 kinase. Analysis of a nonpathogenic Ngo strain revealed only weak JNK activation. In respect to the molecular components upstream of the JNK signaling cascade, we show that a dominant negative mutant of MAP kinase kinase 4 (MKK4) represses transcription of an AP-1-dependent reporter gene. Regarding upstream stress response factors involved in Ngo-induced MKK4/JNK/AP-1 activation, we identified p21-activated kinase (PAK) but not MAPK/ERK kinase kinase (MEKK1). Inhibition of small GTPases including Rac1 and Cdc42 by Toxin B prevented JNK and AP-1 activation. Our results indicate that Ngo induce the activation of proinflammatory cytokines via a cascade of cellular stress response kinases involving PAK, which directs the signal from the Rho family of small GTPases to JNK/AP-1 activation.

Bacterial Proteins↗
PubMed1998

Hexokinase 2 from Saccharomyces cerevisiae: regulation of oligomeric structure by in vivo phosphorylation at serine-14.

Homodimeric hexokinase 2 from Saccharomyces cerevisiae is known to have two sites of phosphorylation: for serine-14 the modification in vivo increases with glucose exhaustion [Kriegel et al. (1994) Biochemistry 33, 148-152], while for serine-157 it occurs in vitro with ATP in the presence of nonphosphorylateable five-carbon analogues of glucose [Heidrich et al. (1997) Biochemistry 36, 1960-1964]. We show now by site-directed mutagenesis and sedimentation analysis that serine-14 phosphorylation affects the oligomeric state of hexokinase, its substitution by glutamate causing complete dissociation; glutamate exchange for serine-157 does not. Phosphorylation of wild-type hexokinase at serine-14 likewise causes dissociation in vitro. In view of the higher glucose affinity of monomeric hexokinase and the high hexokinase concentration in yeast [Womack, F., and Colowick, S. P. (1978) Arch. Biochem. Biophys. 191, 742-747; Mayes, E. L., Hoggett, J. G., and Kellett, G. L. (1983) Eur. J. Biochem. 133, 127-134], we speculate that the in vivo phosphorylation at serine-14 as transiently occurring in glucose derepression might provide a mechanism to improve glucose utilization from low level and/or that nuclear localization of the monomer might be involved in the signal transduction whereby glucose causes catabolite repression.

Amino Acid Sequence↗
PubMed1998

Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin.

OBJECTIVE: To evaluate the effect of intracutaneous injections of botulinum toxin type A on excessive focal hyperhidrosis. DESIGN: Therapeutic before-and-after trial over 4 months. SETTING: Neurological and dermatological university departments. PATIENTS: Eleven patients with excessive axillary, palmar, or plantar hyperhidrosis fulfilling the following criteria: (1) local and systemic drug therapy had failed to improve their symptoms; (2) the patients were severely disabled with respect to their occupation and social activities; and (3) a successful treatment by botulinum toxin would obviate the need for destructive surgical procedures. INTERVENTIONS: Three mouse units of botulinum toxin (Botox) per 4-cm2 skin area was injected intracutaneously in 16 axillae, 8 palms, and 2 soles. MAIN OUTCOME MEASURES: Reduction of hyperhidrosis as documented by the Minor iodine-starch test and gravimetrical assessment of local spontaneous sweat production measured over 1 minute. RESULTS: In all patients, botulinum toxin completely abolished sweating in the injected areas (P<.001) within 3 to 7 days. No relevant adverse effects occurred and no clinical recurrence of hyperhidrosis was observed within the follow-up period of up to 5 months. Occasionally, subclinical reactivation of sweat gland function was observed 4 months after treatment. CONCLUSIONS: Intracutaneous botulinum toxin seems preferable to any hitherto used conservative or surgical procedures and may become the therapy of choice in pathological focal hyperhidrosis.

Adult↗
PubMed1998

Selective degeneration of sudomotor fibers in Ross syndrome and successful treatment of compensatory hyperhidrosis with botulinum toxin.

We report a 5-year follow-up of a patient with Ross syndrome. A biopsy of the anhidrotic skin immunostained with protein gene product 9.5 visualized by confocal microscopy revealed selective loss of sudomotor fibers, whereas epidermal innervation remained intact, providing the first morphologic evidence of selective loss of sudomotor fibers in this syndrome. Among the different treatment strategies employed for the patient's disabling segmental hyperhidrosis, intracutaneous injection of botulinum toxin A was the most helpful.

Adaptation, Physiological↗
PubMed1998

Imaging the pre- and postsynaptic side of striatal dopaminergic synapses in idiopathic cervical dystonia: a SPECT study using [123I] epidepride and [123I] beta-CIT.

There is increasing evidence that a dysfunction of the dopaminergic system may be involved in the pathogenesis of idiopathic dystonia. To visualize possible alterations of the pre- and postsynaptic side of striatal dopaminergic synapses, SPECT studies using the radiotracers [123I] epidepride and [123I] beta-CIT were performed in 10 patients with idiopathic cervical dystonia. Eleven age- and sex-matched subjects served as controls. [123I] Epidepride is a new highly affine marker of D2 receptors, and [123I] beta-CIT binds to dopamine transporters on dopaminergic nerve endings. [123I] Epidepride binding was significantly reduced in both striata of dystonia patients compared with controls (p < 0.05). In contrast, striatal [123I beta-CIT uptake did not differ from controls. We conclude that dopaminergic dysfunction in idiopathic focal dystonia mainly involves postsynaptic mechanisms and suggest a disturbance of the indirect pathway of the motor circuit resulting in a disinhibited thalamocortical stimulation.

Adult↗
PubMed1998

1H magnetic resonance spectroscopy of the lentiform nucleus in primary focal hand dystonia.

Several radiologic findings point toward the lentiform nucleus as a possible site of lesion in primary dystonia. Histologic examinations, however, have shown inconsistent results. 1H-magnetic resonance spectroscopy (MRS) has proved helpful to assess neuronal degeneration in a variety of basal ganglia disorders. MRS data of dystonia patients are, however, lacking so far. 1H-MRS centered on the lentiform nuclei was performed in 14 patients with primary focal hand dystonia and in 12 healthy control subjects using a 1.5-T MR imager. No statistically significant differences of N-acetylaspartate/creatine and lactate/creatine ratios were found between patients and control subjects. Based on these data, the authors found no evidence that primary focal dystonia was associated with a conspicuous loss of lentiform nucleus neurons or a marked disturbance of the aerobic metabolism, although minor abnormalities cannot be excluded because of the possibly limited sensitivity of the method.

Adult↗
PubMed1998

[Recurrent transverse myelitis. 2 cases and review of the literature].

Recurrent transverse myelitis is a rare inflammatory demyelinating disorder, which is distinguished from acute monophasic transverse myelitis and from MS. We present two patients with recurrent transverse myelitis, who developed an acute remitting tetraparesis and sensible deficits with a cervical level. They were followed for 4 and 5 years. MRI showed an isolated lesion with contrast enhancement in the spinal cord but no pathological cranial findings. Oligoclonal bands were negative in repeated lumbar punctures. One patient showed lymphocytic pleocytosis during the first and second attack. Somatosensory and motor evoked potentials were abnormal during relapses while visually and brainstem acoustically evoked potentials (VEP and BAEP) stayed within limits. Laboratory examinations for bacterial, viral or parasitic infections, antinuclear antibodies, Angiotensin-converting enzyme and the sedimentation rate were also normal. The differential diagnosis will be discussed in view of previously reported series. We give a review of the current literature and discuss the differential diagnoses.

Adult↗
PubMed1998

Ribose-5-phosphate isomerase from Saccharomyces cerevisiae: purification and molecular analysis of the enzyme.

Purification and molecular analysis of ribose-5-phosphate isomerase (EC 5.3.1.6) from Saccharomyces cerevisiae is described first time. The enzyme was enriched from a haploid deletion mutant containing the wild-type gene on a multicopy plasmid elaborating the following steps: ammonium sulphate precipitation, interfacial salting out on Sepharose 6B, high performance liquid chromatography on Fractogel EMD DEAE and on Resource Phenyl. The enzyme activity was found to be rather unstable possibly caused by removal of stabilizing cofactors or proteins during the purification procedure. The purified enzyme showed a hyperbolic dependence on the substrate ribose-5-phosphate with a K(m)-value of 1.6 +/- 0.3 mmol/l. For the native enzyme a molecular mass of 115 +/- 10 kDa was determined as found by saccharose density gradient centrifugation, sedimentation equilibrium analysis, size exclusion chromatography and polyacrylamide gel electrophoresis. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blotting revealed one band with a molecular mass of 31 +/- 2 kDa. Thus, the native enzyme is composed of four subunits of identical size. The molecular mass of the subunit and the identified N-terminal sequence of 33 amino acids fits well the 258 amino acid protein encoded by the S. cerevisiae RKI open reading frame, which was characterized previously only by increasing specific activities of ribose-5-phosphate isomerase in cells after cloning the gene. On the basis of the conserved amino acids an alignment of the amino acid sequence of ribose-5-phosphate isomerase from yeast with those of the enzyme from mouse, spinach and Escherichia coli is presented.

Aldose-Ketose Isomerases↗
PubMed1998

Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin.

The objective was to evaluate whether removal of neutralising antibodies potentially resensitises a secondary non-responder to botulinum neurotoxin A (BoNT/A). Neutralising antibodies directed against BoNT/A are produced during long term treatment with BoNT/A-hemagglutinin complex in up to 10% of patients with cervical dystonia. These patients become secondary non-responders. Other serotypes of BoNT are not yet generally available and may also bear the risk of inducing antibody formation. Plasma exchange (PE) (one treatment cycle) and immunoadsorption on a protein A column (IA-PA; three treatment cycles) was employed over 15 months to remove neutralising antibodies from a severely disabled secondary non-responder with cervical dystonia. After plasma exchange or IA-PA, BoNT/A was reinjected. Antibodies were measured with a sensitive functional toxin neutralising test. Repeated use of plasma exchange and IA-PA depleted neutralising antibodies to below the detection limit and subsequently allowed successful BoNT/A injection into dystonic muscles. No serious side effects were found related to the depletion of IgG. In conclusion PE or IA-PA performed before BoNT/A readministration may provide an alternative strategy in treating selected secondary non-responders who are severely disabled.

Adult↗
PubMed1998

A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits.

A novel protein complex has been identified in human cells that has a molecular mass of approximately 450 kDa. It consists of at least eight different subunits including JAB1, the Jun activation-domain binding protein 1, and Trip15, the thyroid hormone receptor-interacting protein 15. The purified complex contains COP9 and COP11 protein homologs and is very similar, if not identical, to the plant COP9 complex involved in light-mediated signal transduction. The isolated JAB1-containing particle has kinase activity that phosphorylates IkappaBalpha, the carboxy terminus of p105, and Ser63 and/or Ser73 of the amino-terminal activation domain of c-Jun. The phosphorylation of c-Jun requires the carboxy terminus of the protein containing the DNA binding and dimerization domains. Three subunits of the new complex--Sgn3, Sgn5/JAB1, and Sgn6--exhibit sequence similarities to regulatory components of the 26S proteasome, which could indicate the existence of common substrate binding sites. Immunofluorescence staining reveals that the new complex shows a subcellular distribution similar to that of the 26S proteasome. The functional relationship of the two particles in regulating transcriptional activity is discussed. Considering the putative role of the complex in signal transduction and its widespread occurrence, we suggest the name JAB1-containing signalosome.

Amino Acid Sequence↗
PubMed1998

Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer.

CD66a (BGP, C-CAM) is an adhesion molecule of the carcinoembryonic antigen family that has been shown to be down-regulated in colorectal, prostate, and breast cancers. The purpose of the present study was to determine its expression pattern in the normal human endometrium and in endometrial neoplasia. For this purpose, we performed immunohistochemistry using the 4D1/C2 monoclonal antibody on a series of 24 normal endometrial samples and 47 endometrial carcinomas. Strong CD66a expression was observed in glandular and luminal epithelial cells of the normal endometrium with a consistent localization at the apical poles of these cells throughout the cycle. In late secretory (premenstrual) phase, loss of cellular polarity resulted in a membranous expression pattern in some glandular cells. In the analyzed tumor samples increasing areas with a complete loss of expression were observed with increasing malignancy grade. The apical expression pattern of the normal epithelium was changed to a membranous all-around pattern in 55% of the tumors, mostly in solid areas. This change correlated with malignancy grade and could be observed in 3 of 15 G1 tumors, 4 of 12 G2 tumors, 11 of 12 G3 tumors, and 8 of 8 serous-papillary carcinomas. Areas with membranous expression pattern could be observed along with areas with a normal apical expression pattern in lower grade carcinomas and with areas with complete loss of expression in high grade tumors. Northern blot analysis showed a loss of mRNA expression in tumor samples and HEC-1B endometrial adenocarcinoma cells. Loss of protein expression in the tumor samples was also observed by Western blot. In conclusion, CD66a protein expression is dysregulated in endometrial carcinomas, showing reduction or loss of expression with increasing malignancy grade and a change from the apical to a membranous localization.

Antigens, CD↗
PubMed1997

Neisseria gonorrhoeae epithelial cell interaction leads to the activation of the transcription factors nuclear factor kappaB and activator protein 1 and the induction of inflammatory cytokines.

We have studied the effect of human bacterial pathogen Neisseria gonorrhoeae (Ngo) on the activation of nuclear factor (NF)-kappaB and the transcriptional activation of inflammatory cytokine genes upon infection of epithelial cells. During the course of infection, Ngo, the etiologic agent of gonorrhea, adheres to and penetrates mucosal epithelial cells. In vivo, localized gonococcal infections are often associated with a massive inflammatory response. We observed upregulation of several inflammatory cytokine messenger RNAs (mRNAs) and the release of the proteins in Ngo-infected epithelial cells. Moreover, infection with Ngo induced the formation of a NF-kappaB DNA-protein complex and, with a delay in time, the activation of activator protein 1, whereas basic leucine zipper transcription factors binding to the cAMP-responsive element or CAAT/enhancer-binding protein DNA-binding sites were not activated. In supershift assays using NF-kappaB-specific antibodies, we identified a NF-kappaB p50/p65 heterodimer. The NF-kappaB complex was formed within 10 min after infection and decreased 90 min after infection. Synthesis of tumor necrosis factor alpha and interluekin (IL)-1beta occurred at later times and therefore did not account for NF-kappaB activation. An analysis of transiently transfected IL-6 promoter deletion constructs suggests that NF-kappaB plays a crucial role for the transcriptional activation of the IL-6 promoter upon Ngo infection. Inactivation of NF-kappaB conferred by the protease inhibitor N-tosyl--phenylalanine chloromethyl ketone inhibited mRNA upregulation of most, but not all, studied cyctokine genes. Activation of NF-kappaB and cytokine mRNA upregulation also occur in Ngo-infected epithelial cells that were treated with cytochalasin D, indicating an extracellular signaling induced before invasion.

Base Sequence↗