Th2/Th17 cell associated cytokines found in seroma fluids after breast cancer surgery.

PURPOSE: The development of a seroma after breast cancer surgery is a common postoperative complication seen after simple mastectomy and axillary surgery. We could recently demonstrate that breast cancer patients undergoing a simple mastectomy with subsequent seroma formation developed a T-helper cell increase within the aspirated fluid measured by flow cytometry. The same study revealed a Th2 and/or a Th17 immune response in peripheral blood and seroma fluid of the same patient. Based on these results and within the same study population, we now analyzed the Th2/Th17 cell associated cytokine content as well as the best known clinical important cytokine IL-6. METHODS: Multiplex cytokine measurements (IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22) were done on 34 seroma fluids (Sf) after fine needle aspiration of patients who developed a seroma after a simple mastectomy. Serum of the same patient (Sp) and that of healthy volunteers (Sc) were used as controls. RESULTS: We found the Sf to be highly cytokine rich. Almost all analyzed cytokines were significantly higher in abundance in the Sf compared to Sp and Sc, especially IL-6, which promotes Th17 differentiation as well as suppresses Th1 differentiation in favor of Th2 development. CONCLUSION: Our Sf cytokine measurements reflect a local immune event. In contrast, former study results on T-helper cell populations in both Sf and Sp tend to demonstrate a systemic immune process.

Genetic Engineering of Oligotropha carboxidovorans Strain OM5-A Promising Candidate for the Aerobic Utilization of Synthesis Gas.

Due to climate change and worldwide pollution, development of highly sustainable routes for industrial production of basic and specialty chemicals is critical nowadays. One possible approach is the use of CO2- and CO-utilizing microorganisms in biotechnological processes to produce value-added compounds from synthesis gas (mixtures of CO2, CO, and H2) or from C1-containing industrial waste gases. Such syngas fermentation processes have already been established, e.g., biofuel production using strictly anaerobic acetogenic bacteria. However, aerobic processes may be favorable for the formation of more costly (ATP-intensive) products. Oligotropha carboxidovorans strain OM5 is an aerobic carboxidotrophic bacterium and potentially a promising candidate for such processes. We here performed RNA-Seq analysis comparing cells of this organism grown heterotrophically with acetate or autotrophically with CO2, CO, and H2 as carbon and energy source and found a variety of chromosomally and of native plasmid-encoded genes to be highly differentially expressed. In particular, genes and gene clusters encoding proteins required for autotrophic growth (CO2 fixation via Calvin-Benson-Bassham cycle), for CO metabolism (CO dehydrogenase), and for H2 utilization (hydrogenase), all located on megaplasmid pHCG3, were much higher expressed during autotrophic growth with synthesis gas. Furthermore, we successfully established reproducible transformation of O. carboxidovoransvia electroporation and developed gene deletion and gene exchange protocols via two-step recombination, enabling inducible and stable expression of heterologous genes as well as construction of defined mutants of this organism. Thus, this study marks an important step toward metabolic engineering of O. carboxidovorans and effective utilization of C1-containing gases with this organism.

Autosomal dominant congenital nystagmus is not linked to 6p12, 7p11, and 15q11 in a German family.

PURPOSE: Congenital nystagmus (CN) is an eye-movement disorder that usually starts within the first months of life. Autosomal dominant, autosomal recessive, and X-chromosomal pedigree patterns are observed. Causative genes are yet unknown. Several loci were implicated to contain disease-relevant genes for autosomal dominant CN (AD CN). AD CN cosegregated with a balanced translocation of 7;15 in a family. In a large black pedigree linkage was demonstrated to 6p12. DESIGN: In this study, we describe a large German family with AD congenital nystagmus. Linkage of AD in this family was tested with previously implicated loci. METHODS: Affected family members and unaffected members underwent genetic analysis. Key family members underwent ophthalmologic testing and oculography. RESULTS: No linkage of AD CN to the implicated loci on 6p12, and 7p11, and 15q11 was found in this study. CONCLUSION: In the presented pedigree genes on 15q11, and on the assumption of full penetrance, 6p12 and 7p11 are not involved in the development of AD congenital nystagmus.

Enhancing recognition of early Parkinsonism in the community.

Because Parkinsonism is underdiagnosed in the community, we have validated screening modalities in the field setting and developed a screening procedure to enhance recognition of undiagnosed patients. In a first survey, we identified suspect cases among patients consulting 9 general practitioners (GPs) over a 3-week period using in parallel: (1) a published questionnaire; (2) a standardized examination by the GPs; (3) clinical impression of the GPs; or (4) pre-established diagnoses. Parkinsonism was ascertained by two neurologists with a 1-year follow-up and FP-CIT-SPECT. In total, 1,411 patients consulted the GPs, 1,030 participated in the study, 87 possible cases were identified by at least one of four screening modalities, 12 suffered from Parkinsonism, and 4 of these 12 were de novo cases. Statistical analysis demonstrated that with appropriate evaluation, the questionnaire is highly sensitive and excludes most nonaffected persons, and that the GPs' clinical impression is more specific. We therefore tested in a second survey the efficacy of a serial screening, starting with the questionnaire, followed by a standardized GP evaluation, and then by neurological examination. Of 1,353 participants seen by 9 GPs during a 3-week period, 5 de novo cases were identified. This simple screening protocol significantly enhances recognition of incipient Parkinsonism.