Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0272170 (SDS)
 50,377 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Borrelia burgdorferi sensu lato has been subdivided into three genospecies: B. burgdorferi sensu stricto, B. garinii, and B. burgdorferi group VS461. Sixty-eight isolates cultured from patients and 26 strains from ticks were characterized with use of SDS-PAGE, western blotting, and rRNA gene restriction analysis. Fifty-seven of 58 strains obtained from the skin of 70 patients who had erythema migrams or acrodermatitis chronica atrophicans were of group VS461, whereas the genotype of the remaining strain was unidentifiable. Of 10 strains cultured from CSF (n = 3) and skin (n = 7) of 20 patients with extracutaneous symptoms of Lyme borreliosis, nine were B. garinii and one was B. burgdorferi sensu stricto. Of these 20 patients, 17 had neuroborreliosis, one had arthritis and carditis, one had myalgia, and one had erythema and arthralgia. All 26 isolates from ticks were of group VS461. In conclusion, infections due to group VS461 and B. garinii are associated with cutaneous and extracutaneous symptoms, respectively. Our findings suggest that B. burgdorferi genotypes have different pathogenic potentials.
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PMID:Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. 790 58

In this study the Authors analyze 380 acoustic neuroma removals carried out from 1972 to 1992 focusing their attention on 90 attempts to save hearing by employing a suboccipital approach. In this series the facial nerve was preserved in 99% of the cases with completely normal function in 78%. The cochlear nerve was anatomically preserved in 96% of the subjects. According to the Shelton-Brackmann classification applied to evaluate hearing results, good hearing (Class A = PTA < or = 30 dB; SDS > or = 70%) was obtained in 12% of the cases, serviceable hearing (Class B = PTA < or = 50 dB; SDS > or = 50%) in 13%, measurable hearing (Class C = any measurable hearing) in 19% and anacusis (Class D) in 56% of the patients. CSF leak occurred in 6.6% of the cases, meningitis in 2.2%, paresis or paralysis of the ninth and tenth cranial nerves in 3% and ataxia in 2%. In acoustic neuroma surgery, hearing preservation is a new but complicated topic. In fact, some operative steps--such as the separation of tumor from nerves and arteries, tumor mass reduction, exposure of the end of the IAC--certainly influence surgical results, but are a matter of uncontrollable variance even within series from the same surgeon and render hearing preservation an innovative idea still awaiting, however, a controllable procedure. The ethical feasibility of hearing preservation is confirmed by our results in which hearing preservation attempts using a suboccipital approach have the same morbidity that the translabyrinthine route would have in the same patient.
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PMID:[The sub-occipital approach in functional surgery of acoustic neuroma]. 813 95

Recombinant human macrophage colony-stimulating factor (rhM-CSF) promotes macrophage proliferation and activity. rhM-CSF clinical trials are currently in progress and require a stable, pharmaceutically acceptable dosage form. This report documents pH effects on rhM-CSF degradation profiles in aqueous solution, with an emphasis on identifying degradation products. Thus, highly purified rhM-CSF was maintained at 30 to 50 degrees C in solutions adjusted to pH 2 to 10. Stressed samples were analyzed by SDS-PAGE, reverse-phase HPLC, size exclusion HPLC, scanning microcalorimetry, and murine bone marrow activity. The results show maximal protein stability in the region pH 7 to 8. Degradation product chromatographic and electrophoretic analyses show distinctly different degradation product profiles in acidic versus alkaline solution. For samples stressed in acidic solution, degradation products were isolated chromatographically and electrophoretically. These degradation products were characterized by N-terminal amino acid sequencing, fast-atom bombardment mass spectrometry, and peptide mapping. The results show that the major degradation pathway in acidic solution involves peptide cleavage at two sites: aspartate169-proline170 and aspartate213-proline214. A third potential cleavage site (aspartate45-proline46) remains intact under conditions that cleave Asp169-Pro170 and Asp213-Pro214. In alkaline solution, degradation proceeds via parallel cleavage and intramolecular cross-linking reactions. A beta-elimination mechanism is proposed to account for the degradation in alkaline solution. Consistent with literature observations, the rhM-CSF N-terminal cleavage products retain biological activity.
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PMID:Degradation pathways for recombinant human macrophage colony-stimulating factor in aqueous solution. 837 55

In many immunoinflammatory diseases, macrophages, by producing interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), stimulate protease secretion in fibroblasts, thus contributing to tissue destruction. Monocyte/macrophage activation is prompted by soluble factors released by activated T cells as well as by cell-cell contact. Indeed, previous studies have shown that monocytes exposed to paraformaldehyde (PFA)-fixed, activated T cells produced high amounts of IL-1 beta. In this report, we used the T cell line HUT-78 to further characterize the T cell factor(s) responsible for monocyte activation by cell-cell contact. After subcellular fractionation, most of the activity was found in the cellular membrane fraction of PHA/PMA-stimulated HUT-78 cells, and proved to be due to glycoproteins, following trypsin digestion and tunicamycin treatment. HUT-78 cells acquired the capacity to stimulate monocytic cells after as little as 1h of stimulation. De novo protein synthesis was required for the expression of the IL-1 beta inducing factor, as shown by cycloheximide treatment. When membrane proteins of PHA/PMA-stimulated HUT-78 cells were separated on SDS-polyacrylamide gel, a peak of stimulatory activity was observed at Mr--25-35 x 10(3). By using specific cytokine inhibitors or blocking mAbs, we ascertained that cell-associated cytokines (IL-1, IL-2, IFN gamma and GM-CSF) were not involved in monocyte activation by cell contact. Anti-CD2 and -CD11a (LFA-1) mAbs partially blocked IL-1 beta production by -25% and -35%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69. 849 Jan 1

Colony-stimulating factor-1 (CSF-1) is synthesized as a secreted or membrane-bound molecule. We investigated whether osteoblastic cells produce these forms of CSF-1. Glutaraldehyde-fixed cell layers supported proliferation of the macrophage cell line BAC1.2F5, suggesting the presence of membrane- or/and matrix-associated CSF-1. Furthermore, CSF-1 activity could be either extracted from the matrix or released from the cell membrane. A neutralizing antiserum against CSF-1 inhibited these activities. After labeling the cellular proteins with [35S] met/cys or [35S] SO4(2-), CSF-1 was immunoprecipitated and analyzed by SDS-PAGE. Under nonreducing conditions, bands with MW more than 200, 200, 100, and 50 kd were detected. These bands shifted to lower MW under reducing conditions. Treatment with chondroitin lyase ABC decreased the MW of the 200 kd monomer, proving the proteoglycan structure. Much smaller quantities of CSF-1 were found in the matrix extract than in the conditioned medium. Transforming growth factor beta (TGF-beta) increased both the synthesis of CSF-1 and its accumulation in the matrix. CSF-1 released with trypsin from the membrane fraction yielded on SDS-PAGE a band with MW of 60 and 30 kd under nonreducing and reducing conditions, respectively. Transcripts encoding both the secreted and the membrane-associated forms of the cytokine were detected in osteoblasts by reverse transcription polymerase chain reaction. These data indicate that osteoblastic cells produce the secreted forms, either remaining in the culture supernatant, or being associated to the matrix, and the membrane associated form of CSF-1.
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PMID:Synthesis of membrane- and matrix-bound colony-stimulating factor-1 by cultured osteoblasts. 859 91

The study deals with 570 strains of Neisseriaceae isolated between 1989 and 1994 in Mali: 396 of the strains were isolated from samples of cerebrospinal fluid and 174 from the throat. Serogroup C accounted for 55% of all strains. Antigenic structure was determined by ELISA, SDS-PAGE and transfer to nitrocellulose membrane for immunoblotting with monoclonal antibodies produced at the Max Planck Institute for Molecular Genetics. For serogroup A, the class 1 protein types found were P1.7 for strains isolated prior to 1994 and P1.9 for strains isolated in 1994. P1.7 is specific to clone IV-1 and P1.9 to clone III-1, which was responsible for the 1994 epidemic. All strains of serogroup C isolated from fluid CSF and most strains isolated from the throat exhibit a new type of class 1 protein which the authors have designated P1.y. P1.y is characteristic of Malian strains of serogroup C; it is rare or absent in strains from other countries (Burkina Faso, Ghana, Italy, USA). The nucleotide sequence of the gene expressing P1.y and the corresponding amino acid sequence were determined at the National Institute for Biological Standards and Control, England.
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PMID:[Molecular epidemiology of meningococcal meningitis in Mali: isolation of a new class 1 protein variant (P1.y)]. 892 55

Like other cytokines, granulocyte colony-stimulating factor (G-CSF) activates a complex array of signal transduction pathways involving multiple kinases and phosphatases. We sought to identify phosphoproteins specific to G-CSF signaling. Using 2D-SDS-PAGE of 32P-labeled cytosolic extracts, we compared phosphoprotein patterns of NFS-60 cells treated with G-CSF or interleukin-3 (IL-3). We also compared the patterns found after stimulation of M-NFS-60 cells with macrophage-CSF (M-CSF). A large number of phosphoproteins were found that were specific for the G-CSF response. Their distribution contrasted with that of Erk-1-related spots, identified by Western blotting, which were common to G-CSF, M-CSF (CSF-1), and IL-3 responses. The activation of Erk-1 by these cytokines was confirmed by in vitro kinase assays. The 2D-SDS-PAGE approach was also used to demonstrate that a series of unrelated G1 phase inhibitors of the mitogenic action of G-CSF elicited both common and diverse protein phosphorylation changes in G-CSF-treated NFS-60 cells that were not dependent on the inhibition of Erk-1 activity, as demonstrated by both in vitro kinase assays and 2D-SDS-PAGE. Therefore, 2D-SDS-PAGE has potential to dissect both the signal transduction pathways lying downstream of the G-CSF receptor (and of the receptors for other CSFs) and also the site of action of proliferation inhibitors.
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PMID:Identification of phosphoproteins specific to granulocyte colony-stimulating factor-mediated signaling using 2D-SDS-PAGE. 905 13

The cAMP analogue 8-bromo-cAMP (8BrcAMP) inhibits granulocyte-colony-stimulating factor (G-CSF)-stimulated DNA synthesis in myeloid NFS-60 cells. We examined the effect of 8BrcAMP addition on the G-CSF-stimulated extracellular signal-related protein kinase 1 (Erk-1), p21ras and Raf-1 activation. The Erk-1 activity was not down-regulated by the increase in intracellular cAMP levels, whereas p21ras and Raf-1 activities were, suggesting that Erk-1 activity might not be dependent on upstream p21ras and/or Raf-1 activity in this system. To explore this possibility further, we sought to determine whether there were downstream substrates of Raf-1 that were distinguishable from those of Erk-1 by using two-dimensional SDS/PAGE analysis of the protein phosphorylation patterns of NFS-60 cell cytosolic extracts treated with exogenous Raf-1 or Erk-1 in the presence of [gamma-32P]ATP. The two phosphorylation patterns were found to have many differences. To gain further insights into the possible relevance of these phosphorylation patterns and as an approach to exploring in more detail the inhibitory effect of 8BrcAMP, two-dimensional SDS/PAGE analysis was performed on the cytosolic extracts of 32P-labelled NFS-60 cells treated with G-CSF, in the absence or presence of 8BrcAMP. It was found that the phosphorylated proteins whose appearance was specific to the action of exogenous Raf-1 were sensitive to the action of 8BrcAMP in vivo, whereas those whose appearance was specific to the action of exogenous Erk-1 alone, or common to the actions of Raf-1 and Erk-1, were 8BrcAMP-insensitive. The results are consistent with a Raf-1-independent pathway for Erk-1 activation in G-CSF treated myeloid cells, and a number of potential downstream substrates of these kinases have been identified for further characterization.
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PMID:cAMP suppresses p21ras and Raf-1 responses but not the Erk-1 response to granulocyte-colony-stimulating factor: possible Raf-1-independent activation of Erk-1. 907 46

The CSF and sera of 185 patients with multiple sclerosis (MS), 130 patients with other inflammatory diseases of the CNS (OID) and 50 patients with spinal disc syndrome (controls) were investigated for IgG-antibodies to CNS proteins by SDS-PAGE and immunoblotting and by isoelectric focusing combined with affinity blotting. IgG-antibodies to CNS proteins in serum (immunoblotting) were detected in 18 patients with MS (10%), in 29 patients with OID (22%) and in four controls (8%). Intrathecal synthesis of IgG-antibodies to CNS proteins was demonstrated in 11 patients with MS (6%), in 37 patients with OID (28%) and in none of the controls. In 4/11 patients with MS intrathecally produced antibodies were shown to be specific for glial fibrillary acidic protein (GFAP). Of patients with MS, 180 displayed oligoclonal IgG-bands in the CSF. Specificity of these bands for CNS proteins was demonstrated only in 2/180 specimens (1%). These findings indicate, that in most patients with MS oligoclonal IgG-bands in the CSF do not contain relevant amounts of antibodies to CNS proteins.
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PMID:IgG-antibodies to CNS proteins in patients with multiple sclerosis. 911 Sep 24

The development of recombinant-met human granulocyte-colony stimulating factor (r-metHuG-CSF) for clinical use has had a major influence on the treatment of many diseases. This impact has perhaps been greatest for treatment of severe chronic neutropenia (SCN) conditions for which there were no predictably effective treatment before the availability of these growth factors, particularly r-metHuG-CSF (Filgrastim, Amgen Inc, Thousand Oaks, CA; or Lenograstim, Rhone-Poulenc Rorer, Milan, Italy). Based on careful studies in many countries it is now known that more than 95% of these patients will respond promptly to r-metHuG-CSF treatment with normalization of the blood neutrophil levels and reduction in the occurrence of both major and minor consequences of their severe neutropenia. The availability of this treatment will undoubtedly lead to much additional research on the mechanisms governing neutrophil production and the basic mechanisms that can cause neutropenia among patients who have SCN. Among patients who have SCN those who are diagnosed to have severe congenital neutropenia (Kostmann's syndrome) or Shwachman-Diamond syndrome are at risk of developing myelodysplasia and/or acute myelogenous leukemia. The role of r-metHuG-CSF in facilitating the risk remains to be determined. Thus, it is important that long-term evaluation of the safety and efficacy of treatment of SCN and cooperation in research on these rare conditions proceed under the auspices of an international registry monitoring the clinical outcome of patients with severe congenital neutropenia.
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PMID:Severe chronic neutropenia: pathophysiology and therapy. 934 77


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