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1004 Publications visible to you, out of a total of 1004
Neuronal hypoxia in vitro: investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnThe therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral … ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood.\backslashr\backslashnMETHODS\backslashr\backslashnA human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array.\backslashr\backslashnRESULTS\backslashr\backslashntMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% +/- 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% +/- 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures.\backslashr\backslashnCONCLUSION\backslashr\backslashnOur data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes. BACKGROUND The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. METHODS A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. RESULTS tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% +/- 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% +/- 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. CONCLUSION Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes.

Authors: Doreen M. Reich, Susann Hau, Tobias Stahl, Markus Scholz, Wilfried Naumann, Frank Emmrich, Johannes Boltze, Manja Kamprad

Date Published: 1st Dec 2008

Publication Type: Journal article

Zur Bedeutung der Genvariante PTPN22 620W für die Rheumatologie
Genetical Statistics and Systems Biology

Abstract (Expand)

PTPN22 620W is regarded as the second most important risk factor for type 1 diabetes and rheumatoid arthritis. Here we describe aspects of the molecular biology of the enzyme and its function, the … geographical distribution of the 620W variant, as well as its importance in less frequent rheumatic diseases.

Authors: Inga Melchers, Peter Ahnert

Date Published: 1st Nov 2008

Publication Type: Journal article

An evaluation of the polymorphisms Ins16bp and Arg72Pro in p53 as breast cancer risk modifiers in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 and BRCA2 has promoted the investigation of various polymorphisms in the p53 gene as possible risk modifiers … in BRCA1/2 mutation carriers. Specifically, two polymorphisms in p53, c.97-147ins16bp and p.Arg72Pro have been analysed as putative breast cancer susceptibility variants, and it has been recently reported that a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 (No Ins-72Pro) was associated with an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population. In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.

Authors: A. Osorio, M. Pollán, G. Pita, R. K. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Arnold, S. Preisler-Adams, D. Niederacher, W. Hofmann, D. Gadzicki, A. Jakubowska, U. Hamann, J. Lubinski, A. Toloczko-Grabarek, C. Cybulski, T. Debniak, G. Llort, D. Yannoukakos, O. Díez, B. Peissel, P. Peterlongo, P. Radice, T. Heikkinen, H. Nevanlinna, P. L. Mai, J. T. Loud, L. McGuffog, A. C. Antoniou, J. Benitez

Date Published: 1st Sep 2008

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).
GLA - German Lymphoma Alliance

Abstract (Expand)

Recent retrospective studies of heterogeneously treated patients have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B-cell lymphoma … (DLBCL). Here, we investigated the prognostic impact of MYC aberrations analyzed by interphase fluorescence in situ hybridization in 177 patients with de novo DLBCL treated within the two prospective, randomized trials non-Hodgkin's lymphoma NHL-B1 and NHL-B2. MYC aberrations were detected in 14 DLBCL (7.9%). In a univariate analysis compared with MYC-negative DLBCL, MYC-positive cases showed a significantly shorter overall survival (OS) (P=0.047) and relevantly, though not significantly, shorter event-free survival (EFS) (P=0.062). In a Cox model adjusted for the international prognostic index, the presence of a MYC gene rearrangement was the strongest statistically independent predictor of OS (relative risk 3.4, P=0.004) and EFS (relative risk 2.5, P=0.015), and this also held true when the cell-of-origin signature detected by immunohistochemistry was included in the model.

Authors: W. Klapper, H. Stoecklein, S. Zeynalova, G. Ott, F. Kosari, A. Rosenwald, M. Loeffler, L. Trumper, M. Pfreundschuh, R. Siebert

Date Published: 30th Aug 2008

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Malignancy grading, pattern of invasion, and juxtatumoral stromal response (desmoplastic change) in squamous cell carcinoma of the uterine cervix.
ProstataCA

Abstract

Not specified

Authors: L. C. Horn, B. Hentschel, U. D. Braumann

Date Published: 30th Aug 2008

Publication Type: Not specified

Human Diseases: cervical cancer

Studienprotokoll der VISEP-Studie. Entgegnung der SepNet-Studiengruppe
SepNet - German Competence Network Sepsis

Abstract (Expand)

In the commentary by Zander et al. the authors appear concerned about the methods and results of our, at that time, unpublished sepsis trial evaluating hydroxyethyl starch (HES) and insulin therapy. … Unfortunately, the authors’ concerns are based on false assumptions about the design, conduct and modes of action of the compounds under investigation. For instance, in our study the HES solution was not used for maintenance of daily fluid requirements, so that the assumption of the authors that this colloid was used \textquotedblexclusively\textquotedbl is wrong. Moreover, the manufacturer of Hemohes, the HES product we used, gives no cut-off value for creatinine, thus the assumption that this cut-off value was \textquotedbldoubled\textquotedbl in our study is also incorrect. Other claims by the authors such as that lactated solutions cause elevated lactate levels, iatrogenic hyperglycemia and increase O(2) consumption are unfounded. There is no randomized controlled trial supporting such a claim - this claim is neither consistent with our study data nor with any credible published sepsis guidelines or with routine practice worldwide. We fully support open scientific debate. Our study methods and results have now been published after a strict peer-reviewing process and this data is now open to critical and constructive reviewing. However, in our opinion this premature action based on wrong assumptions and containing comments by representatives of pharmaceutical companies does not contribute to a serious, unbiased scientific discourse.

Authors: K. Reinhart, F. M. Brunkhorst, C. Engel, F. Bloos, A. Meier-Hellmann, M. Ragaller, N. Weiler, O. Moerer, M. Gruendling, M. Oppert, S. Grond, D. Olthoff, U. Jaschinski, S. John, R. Rossaint, T. Welte, M. Schaefer, P. Kern, E. Kuhnt, M. Kiehntopf, T. Deufel, C. Hartog, H. Gerlach, F. Stüber, H-D Volk, M. Quintel, M. Loeffler

Date Published: 1st Jul 2008

Publication Type: Journal article

Human Diseases: disease by infectious agent

Genome-wide genetic characterization of an atypical meningioma by single-nucleotide polymorphism array-based mapping and classical cytogenetics
Genetical Statistics and Systems Biology

Abstract (Expand)

Most meningiomas, accounting for about 20% of intracranial tumors, can be cured by surgical removal. Yet, 8-22% of these tumors are classified as atypical or anaplastic (WHO grade II or III, respectively) … presenting with a more aggressive behavior and a high relapse rate. We analyzed genomic alterations of an atypical meningioma using high-density single nucleotide polymorphism arrays (SNP-A) karyotyping combined with GTG-banding, multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH. In accordance to recent studies applying SNP-A karyotyping in different malignancies we found that genomic lesions are present at a higher frequency than predicted by traditional cytogenetics. Most of these aberrations have not been described before. Additionally, we unveiled loss of heterozygosity (LOH) without copy number changes on chromosome regions 1p31.1, 2p16.1, 2q23.3, 6q14.1, 6q21, 9p21.1, 10q21.1, and 14q23.3, suggesting partial uniparental disomy (UPD). UPDs are currently considered to play an important role in the initiation and progression of different malignancies. Furthermore, we detected two de novo reciprocal translocations, t(8;19)(q24;q13) and t(10;16)(q22;q12.1). While GTG-banding and M-FISH data suggested balanced translocations, SNP-A analysis clearly demonstrated imbalances in the same region.

Authors: Wolfgang Krupp, Heidrun Holland, Ronald Koschny, Manfred Bauer, Ralf Schober, Holger Kirsten, Michela Livrea, Jürgen Meixensberger, Peter Ahnert

Date Published: 1st Jul 2008

Publication Type: Journal article

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