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Medium-chain acyl CoA dehydrogenase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Among infants identified by newborn screening, Zschocke et al. [44] found heterozygosity for the A985G mutation and Y67H in two patients, homozygosity for G267R in one, and S245L in two children of consanguineous parents. None of these patients had clinical disease up to six months of follow up at report. Urinary organic acids were normal in these infants, and their C8/C12 acylcarnitine ratios were lower than in patients with classic disease. Enzyme assay showed higher activity than in classic patients.
Neuroanatomy overview
Published in Michael Y. Wang, Andrea L. Strayer, Odette A. Harris, Cathy M. Rosenberg, Praveen V. Mummaneni, Handbook of Neurosurgery, Neurology, and Spinal Medicine for Nurses and Advanced Practice Health Professionals, 2017
The radial nerve originates as a terminal branch of the posterior cord of the brachial plexus, approximately at the level of the coracoid process. It contains within it fibers from C5 to C7, and a small contribution from C8. However, it is mainly from C7. It is possible to split the posterior cord into its major branches (nerve to lattisimus dorsi, axillary nerve) for several centimeters if this is necessary. Close to the radial nerve origin, a number of branches leave it to supply one or more of the three heads of the triceps. Also, while in the axilla, it gives off the posterior brachial cutaneous nerve supplying a small area on the posterolateral aspect of the arm. The nerve can be approached either medially or laterally to the axillary artery during surgery. If there is a lot of scarring, it is better to find the nerve in the axilla and dissect proximally. Branches of the axillary artery should be preserved, namely, the circumflex humeral vessels (along which the axillary nerve is found) and the profunda brachial artery, with which the radial nerve leaves the axilla. At this point, it is the thickest nerve in the axilla (thicker than the ulnar nerve and the medial cutaneous nerve of the forearm).
Neuro-Oncology
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
Certain cancers may directly affect the nervous system by direct spread, for example breast cancer invading the brachial plexus, or lung cancer infiltrating the C8/T1 cervical roots with deficit including a Horner’s syndrome (Pancoast tumour). This is usually a painful subacute presentation with clear imaging evidence of tumour on MRI, best seen after contrast is given. NHL can rarely present with direct infiltration into the peripheral nervous system (neurolymphomatosis) either as a mono- or polyneuropathy, cranial neuropathy or painful radiculopathy.
Evaluation of physicochemical and functional similarity of a new CHO derived anti-EGFR antibody P-mAb to its reference medicinal product
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Jitender Nandal, Kanti N. Mihooliya, Himanshu Verma, Nidhi Kalidas, Fnu Ashish, Ravi P. N. Mishra, Debendra K. Sahoo
Mass analyses were done using Agilent 6550 iFunnel QTOF liquid chromatography mass spectroscopy (LC/MS) system. RMP and P-mAb samples were diluted to 1.0 mg/ml in 1% formic acid for LC/MS intact mass analysis. For reduction, RMP and P-mAb were diluted to 1.0 mg/ml in reduction buffer (pH 7.5; 25 mM Tris; 25 mM NaCl) and a concentrated tris(2-carboxyethyl) phosphine (TCEP) solution was added to obtain a final TCEP concentration of 5 mM. The solution was incubated at 37 °C for 30 min. The samples were then diluted using 1% formic acid to 0.2 mg/ml. For reduced and deglycosylated mAb subunit analysis, reduced samples were incubated overnight with PNGase F (Promega, USA) in a 1:10 ratio of enzyme to mAb at 37 °C in ammonium bicarbonate buffer (pH 7.8; 50 mM). C8 (150 × 3.0 mm) 300 Å column was used with 1% Trifluoroacetic acid (TFA) in water (buffer A) and 1% TFA acetonitrile (buffer B) as mobile phases. Following equilibration of the column with 90% buffer A and 10% buffer B, 2 µl of sample was loaded on the column with a linear gradient from 10% to 70% B in 15 min, 70–90% B from 15 to 18 min, 90–100% B from 18 to 19 min at a flow rate of 0.4 ml/min and ion chromatogram (TIC) was recorded from 100 to 1000 and 200 to 3200 for intact and reduced samples respectively. The system settings for gas temperature and VCap were kept at 270 °C and 4000 V, respectively. The system was used in positive ion mode for analysis. Agilent MassHunter qualitative analysis software was used to analyse the MS spectra, and the maximum entropy algorithm was used for the deconvolution of spectra (Supplementary Table ST2).
Impaired CXCL12 signaling contributes to resistance of pancreatic cancer subpopulations to T cell-mediated cytotoxicity
Published in OncoImmunology, 2022
Yuan-Na Lin, Marcel O. Schmidt, Ghada M. Sharif, Eveline E. Vietsch, Amber J. Kiliti, Megan E. Barefoot, Anna T. Riegel, Anton Wellstein
Previous studies have identified a correlation between CD8+ T cell infiltration and response to immunotherapy in melanoma and PDAC.8,26 To examine whether resistance to edT cell-mediated PDAC cell killing is related to T cell access to cancer cells, we analyzed PDAC 3D co-cultures for the distribution of cancer and T cells by staining for CD4+ and CD8+ T cells. This analysis allowed us to quantify T cells that only adhere to the cancer spheroid periphery and those which infiltrated into the spheroid (Figure 3). Only spheroids with comparable sizes were subjected to the comparative analysis. The number of CD8+ edT cells that adhered to the spheroids showed no significant differences between parental and resistant cancer cells although D10 cancer cells attracted a higher number of edT cells per spheroid than C8 cancer cells. For both C8 and D10 cancer cell lines there was significantly more CD8+ edT cell infiltration into spheroids from parental cancer cells than spheroids generated from resistant cancer cells (Figure 3(b)). Because the D10 cell line showed more infiltrated CD8+ edT cells than the C8 cell line, we also stained for CD4+ edT cells (Suppl. Fig. S3B). The number of infiltrated or adherent CD4+ edT cells was not significantly different between parental and resistant cells and there were much less infiltrated CD4+ than CD8+ edT cells (Suppl. Fig. S3C).
Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?
Published in Critical Reviews in Toxicology, 2021
Styliani Fragki, Hubert Dirven, Tony Fletcher, Bettina Grasl-Kraupp, Kristine Bjerve Gützkow, Ron Hoogenboom, Sander Kersten, Birgitte Lindeman, Jochem Louisse, Ad Peijnenburg, Aldert H. Piersma, Hans M. G. Princen, Maria Uhl, Joost Westerhout, Marco J. Zeilmaker, Mirjam Luijten
The largest study is on 46 000 adults from the C8 cohort in the mid-Ohio valley, in which residents were exposed for many decades to various PFOA levels through contaminated drinking water and via food, and show a wide range of serum concentrations (Steenland et al. 2009). This study showed median blood PFOS and PFOA levels of 20 and 27 ng/mL, respectively. Notably, for PFOA very high blood levels (up to ∼18 000 ng/mL) were observed in part of the population. Much of the increase is observed at low PFOS/PFOA serum levels and seems to level off at higher levels (above about 50 ng/mL), as also shown by the modeling of the data (EFSA CONTAM Panel 2018a). Another large population with PFAS exposure from contaminated drinking water, predominantly PFOA, is in the Veneto region of Italy (Canova et al. 2020). A cross sectional analysis of PFASs and lipids was carried out in nearly 16 000 people, between 20 and 39 years. The median PFOA serum concentration was 35.8 ng/ml, and the pattern broadly consistent with the C8 study, i.e. increasing cholesterol with PFOA concentration and a steeper slope at lower concentrations. Another recent study on a community, living in a PFAS-polluted area and exhibiting raised serum levels of mainly PFOS (and other PFASs) and to a lesser degree PFOA, also reported positive associations with serum cholesterol (Li et al. 2020). In addition to the cross-sectional analyses associating concurrent serum measurements of PFASs and lipids, the authors included an ecological component showing higher cholesterol in the exposed community compared to subjects sampled in a nearby, non-exposed community.