1.Application of gene expression profiling in molecular classification, prognosis and therapy of B-cell lymphoma.
Zheng-rong MAO ; Ren ZHOU ; Xin-xia ZHANG ; Hans konrad MUELLER-HERMELINK ; Andreas ROSENWALD
Chinese Journal of Pathology 2009;38(11):785-789
Burkitt Lymphoma
;
classification
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genetics
;
therapy
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Humans
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Leukemia, Lymphocytic, Chronic, B-Cell
;
classification
;
genetics
;
therapy
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Lymphoma, B-Cell
;
classification
;
genetics
;
therapy
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Lymphoma, Follicular
;
classification
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genetics
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therapy
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Lymphoma, Large B-Cell, Diffuse
;
classification
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genetics
;
therapy
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Lymphoma, Mantle-Cell
;
classification
;
genetics
;
therapy
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Prognosis
2.MicroRNA 150-5p Improves Risk Classification for Mortality within 90 Days after Acute Ischemic Stroke.
Natalie SCHERRER ; Francois FAYS ; Beat MUELLER ; Andreas LUFT ; Felix FLURI ; Mirjam CHRIST-CRAIN ; Yvan DEVAUX ; Mira KATAN
Journal of Stroke 2017;19(3):323-332
BACKGROUND AND PURPOSE: Micro ribonucleic acid-150-5p (miR-150-5p) regulates proinflammatory cytokines as well as vessel integrity. We evaluated the incremental prognostic value of logarithm (log) of miR-150-5p plasma levels after ischemic stroke. METHODS: In a prospective cohort study, levels of miR-150-5p were measured within 72 hours of symptom onset in 329 ischemic stroke patients. The outcome measures were unfavorable functional outcome (assessed by the modified Rankin Scale score >2) and mortality within 90 days. Logistic regression and Cox proportional hazards models were fitted to estimate odds ratio (OR), respectively hazard ratio (HR) and 95% confidence interval (CI) for the association between log-miR-150-5p and the outcome measures. The discriminatory accuracy was assessed with the area under the receiver-operating-characteristic curve (AUC) and the incremental prognostic value was estimated with the net reclassification index. RESULTS: After adjusting for demographic and vascular risk factors, lower log-miR-150-5p levels were independently associated with mortality (HR 0.21 [95% CI, 0.08–0.51], P=0.001) but not functional outcome (OR 1.10 [95% CI, 0.54–2.25], P=0.79). Adding log-miR-150-5p improved the discriminatory accuracy of the best multivariate model to predict mortality from an AUC of 0.91 (95% CI, 0.88–0.95) to 0.92 (95% CI, 0.88–0.96 Likelihood-ratio test-P < 0.001), and resulted in a net reclassification index of 37.3% (95% CI, 0.28–0.52). CONCLUSIONS: In patients with ischemic stroke, log-miR-150-5p is a novel prognostic biomarker, highly associated with mortality within 90 days, improving risk classification beyond traditional risk factors.
Area Under Curve
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Biomarkers
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Classification*
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Cohort Studies
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Cytokines
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Humans
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Logistic Models
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MicroRNAs*
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Mortality*
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Odds Ratio
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Outcome Assessment (Health Care)
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Plasma
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Prognosis
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Proportional Hazards Models
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Prospective Studies
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Risk Factors
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Stroke*
3.Gonadal damage and options for fertility preservation in female and male cancer survivors.
Theodoros MALTARIS ; Heinz KOELBL ; Rudolf SEUFERT ; Franklin KIESEWETTER ; Matthias W BECKMANN ; Andreas MUELLER ; Ralf DITTRICH
Asian Journal of Andrology 2006;8(5):515-533
It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization (IVF) after cancer treatment are also presented.
Adult
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Child
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Female
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Fertility
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Humans
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Infertility
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prevention & control
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Male
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Neoplasms
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drug therapy
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radiotherapy
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surgery
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Ovarian Neoplasms
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pathology
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Ovary
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pathology
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Survivors
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Testicular Neoplasms
;
pathology
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Testis
;
pathology
4.Clonality analysis and mutational status of IgVH gene in Hodgkin variant of Richter syndrome.
Zheng-rong MAO ; Andreas ROSENWALD ; Suo-jiang ZHANG ; Ren ZHOU ; Hans Konrad MUELLER-HERMELINK
Chinese Journal of Pathology 2008;37(8):523-528
OBJECTIVETo detect the clonal relationship, the rearrangement, and the mutational status of IgVH gene; the influence of these molecular characteristics on the clinical outcome in Hodgkin variant of Richter syndrome; and the possible molecular pathogenesis in this transformation.
METHODSThe clonal rearrangements and mutational status of IgVH genes were analyzed in Hodgkin variant of Richter syndrome and B-CLL with Reed-Stemberg (R-S)-like cells by GeneScan analysis and sequencing. Semi-nest PCR based on laser capture microdissection was utilized to compare the clonal relationship between B-CLL and R-S/R-Slike cells. Immunohistochemical staining was used to detect the different expressions of ZAP70, p53, IRF-4 and LMP1 in the two components.
RESULTS(1) 5/6 B-CLL cases transformed to Hodgkin lymphoma (HL)/R-S-like cells carried the mutated IgVH genes; (2) 2 cases of R-S cells and 1 case of R-S-like cells were clonally distinct from B-CLL clone and express LMP1, whereas 1 case of R-S-like cells was relating to the surrounding B-CLL cells and did not express LMP1; (3) 2/6 B-CLL cases transformed to HL convey VH4-34 and VH3-48 respectively.
CONCLUSIONS(1) Richter transformation to HL/R-S-like cells evolves from the B-CLL which originates from the germinal center or post germinal center B cells, indicating that different lymphoma cells of different subtypes in Richter syndrome come from different B cell lineage and possibly involve a different pathogenesis and pathway; (2) HL and R-S-like cells evolve from either the B-CLL clone or may develop as a clonally unrelated lymphoma, the independent secondary malignancies are appear to be EBV-positive, possibly as a consequence of the underlying immunodeficiency; (3) The biased usage of IgVH genes suggested a role of antigens involved in the HL variant of Richter syndrome.
Aged ; Aged, 80 and over ; Clone Cells ; pathology ; Female ; Herpesvirus 4, Human ; Hodgkin Disease ; classification ; genetics ; pathology ; virology ; Humans ; Immunoglobulin Variable Region ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Reed-Sternberg Cells ; pathology ; Syndrome
5.Clonality analysis and mutation status of IgVH genes in classic Richter's syndrome.
Zheng-rong MAO ; Andreas ROSENWALD ; Suo-jiang ZHANG ; Ren ZHOU ; Hans Konrad MUELLER-HERMELINK
Chinese Journal of Pathology 2008;37(6):364-370
OBJECTIVETo study the clonal rearrangements and mutation status of IgVH genes in classic Richter's syndrome, the relationship between molecular findings of IgVH gene and clinical outcome, and to deciper the possible molecular mechanism of transformation.
METHODSThe clonal rearrangements and mutation status of IgVH genes were analyzed in cases of classic Richter's syndrome by Genescan and sequencing. Immunohistochemical study for zeta-chain associated protein kinase 70 kDa (ZAP70), p53 and interferon regulation factor 4 (IRF-4) was also performed.
RESULTSSamples of 18 cases of B-chronic lymphocytic leukemia (B-CLL)/ diffuse large B-cell lymphoma (DLBCL,78. 3%) had identical tumor cell clones, whereas DLBCL developed as a clonally independent neoplasm in 5 patients (21.7%). Among the clonally related group, 12 cases carried unmutated VH genes in both B-CLL and DLBCL components and VH3-23, VH3-74 and VH1-2 were accounted for the B-CLL transformation to DLBCL. Immunohistochemical study showed that the transformed DLBCL expressed CD5 in 32.1% of cases, CD23 in 14.3%, ZAP70 in 23.8%, p53 in 80.6% and IRF-4 in 82.6% of the cases respectively. Follow-up data were available in 17 patients with classic Richter's syndrome. The median survival period was 7 months. No significant difference in survival rate was obtained between the clonally related or unrelated groups, between IgVH gene mutated or unmutated groups, and between the groups with or without expression of ZAP70, p53 and IRF-4.
CONCLUSIONSThe ratio of clonally related transformed DLBCL from B-CLL to clonally unrelated DLBCL is 2:1. Clonal transformation to DLBCL predominantly occurs in B-CLL patients carrying unmutated IgVH genes. The biased IgVH gene usage suggests antigens are involved in classic Richter's syndrome. Molecular differences of IgVH genes and very poor clinical outcome of this group of transformed DLBCL indicate that there cases may be regarded as a distinct subset of DLBCL.
Aged ; Aged, 80 and over ; B-Lymphocytes ; pathology ; Genes, p53 ; genetics ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulin Variable Region ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; Lymphoma, B-Cell ; genetics ; Lymphoma, Large B-Cell, Diffuse ; genetics ; Male ; Middle Aged ; Somatic Hypermutation, Immunoglobulin ; genetics ; ZAP-70 Protein-Tyrosine Kinase ; genetics
6.Functional Recovery Not Correlated with Axon Regeneration through Olfactory Ensheathing Cell-Seeded Scaffolds in a Model of Acute Spinal Cord Injury.
Haktan ALTINOVA ; Sven MÖLLERS ; Ronald DEUMENS ; Jose GERARDO-NAVA ; Tobias FÜHRMANN ; Sabien Geraldine Antonia VAN NEERVEN ; Ahmet BOZKURT ; Christian Andreas MUELLER ; Hans Joachim HOFF ; Ingo HESCHEL ; Joachim WEIS ; Gary Anthony BROOK
Tissue Engineering and Regenerative Medicine 2016;13(5):585-600
The implantation of bioengineered scaffolds into lesion-induced gaps of the spinal cord is a promising strategy for promoting functional tissue repair because it can be combined with other intervention strategies. Our previous investigations showed that functional improvement following the implantation of a longitudinally microstructured collagen scaffold into unilateral mid-cervical spinal cord resection injuries of adult Lewis rats was associated with only poor axon regeneration within the scaffold. In an attempt to improve graft-host integration as well as functional recovery, scaffolds were seeded with highly enriched populations of syngeneic, olfactory bulb-derived ensheathing cells (OECs) prior to implantation into the same lesion model. Regenerating neurofilament-positive axons closely followed the trajectory of the donor OECs, as well as that of the migrating host cells within the scaffold. However, there was only a trend for increased numbers of regenerating axons above that supported by non-seeded scaffolds or in the untreated lesions. Nonetheless, significant functional recovery in skilled forelimb motor function was observed following the implantation of both seeded and non-seeded scaffolds which could not be correlated to the extent of axon regeneration within the scaffold. Mechanisms other than simple bridging of axon regeneration across the lesion must be responsible for the improved motor function.
Adult
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Animals
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Axons*
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Collagen
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Forelimb
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Humans
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Rats
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Regeneration*
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Spinal Cord Injuries*
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Spinal Cord*
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Tissue Donors
7.Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage
Martina B. GOELDLIN ; Achim MUELLER ; Bernhard M. SIEPEN ; Madlaine MUELLER ; Davide STRAMBO ; Patrik MICHEL ; Michael SCHAERER ; Carlo W. CEREDA ; Giovanni BIANCO ; Florian LINDHEIMER ; Christian BERGER ; Friedrich MEDLIN ; Roland BACKHAUS ; Nils PETERS ; Susanne RENAUD ; Loraine FISCH ; Julien NIEDERHAEUSER ; Emmanuel CARRERA ; Elisabeth DIRREN ; Christophe BONVIN ; Rolf STURZENEGGER ; Timo KAHLES ; Krassen NEDELTCHEV ; Georg KAEGI ; Jochen VEHOFF ; Biljana RODIC ; Manuel BOLOGNESE ; Ludwig SCHELOSKY ; Stephan SALMEN ; Marie-Luise MONO ; Alexandros A. POLYMERIS ; Stefan T. ENGELTER ; Philippe LYRER ; Susanne WEGENER ; Andreas R. LUFT ; Werner Z’GRAGGEN ; David BERVINI ; Bastian VOLBERS ; Tomas DOBROCKY ; Johannes KAESMACHER ; Pasquale MORDASINI ; Thomas R. MEINEL ; Marcel ARNOLD ; Javier FANDINO ; Leo H. BONATI ; Urs FISCHER ; David J. SEIFFGE ;
Journal of Stroke 2022;24(2):266-277
Background:
and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce.
Methods:
We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031).
Conclusions
Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.
8.A study protocol on the situational analysis on the current practice of screening and treatment of Retinopathy of Prematurity (ROP)
Karina Q. De Sagun-Bella ; Theresa Gladiola B. Merca ; Jane Melissa L. Lim ; Alvina Pauline D. Santiago ; Pearl Tamesis-Villalon ; Andreas Mueller ; Leo D.P. Cubillan
Philippine Journal of Ophthalmology 2013;38(2):94-102
Objective:
The study protocolaims to provide an overview of the current practice of screening and treatment of
ROP in the selected, to estimate the proportion of childhood blindness due to ROP and assess the number of
premature babies at risk for ROP.
Methods:
The study protocol is a descriptive, cross sectional study design using survey questionnaire to be sent
out to pediatric ophthalmologists, vitreo-retina specialists and division heads of the neonatal intensive care units
of different hospitals in a selected area. Student records and medical abstracts from local schools for the blind will
be obtained and will be reviewed. All qualitative data will be reported by frequency distribution and percentages.
Extrapolation on the proportion of ROP in the area will be done.
Conclusion
Results from the study can show an overview of the current situation of ROP in a selected area
and provide the framework for recommendations for programs aimed providing criteria for timely screening and
treatment of ROP to prevent complications such as childhood visual impairment and blindness in the country.
Retinopathy of Prematurity
;