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J Feldmann

Publications and source records attributed to J Feldmann.

At least 37 records · Page 2Linked to original sources

Defective CTLA-4 cycling pathway in Chediak-Higashi syndrome: a possible mechanism for deregulation of T lymphocyte activation.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, also known as CD152) has been shown to play a major role in the regulation of T cell activation. Its membrane expression is highly regulated by endocytosis and trafficking through the secretory lysosome pathway. Chediak-Higashi syndrome (CHS) is an inherited disorder caused by mutations in the lysosomal trafficking regulator gene, LYST. It results in defective membrane targeting of the proteins present in secretory lysosomes, and it is associated with a variety of features, including a lymphoproliferative syndrome with hemophagocytosis. The murine equivalent of CHS, beige mice, present similar characteristics but do not develop the lymphoproliferative syndrome. We show herein that CTLA-4 is present in enlarged, abnormal vesicles in CHS T cells and is not properly expressed at the cell surface after T cell activation, whereas its surface expression is not impaired. It is therefore proposed that the defective surface expression of CTLA-4 by CHS T cells is involved in the generation of lymphoproliferative disease. This observation may provide insight into the role of CTLA-4 in humans.

Abatacept↗

Determination of Ni(CO)4, Fe(CO)5, Mo(CO)6, and W(CO)6 in sewage gas by using cryotrapping gas chromatography inductively coupled plasma mass spectrometry.

Evidence for the occurrence of Ni(CO)4 in addition to Mo(CO)6 and W(CO)6 in fermentation gases from a municipal sewage treatment plant is presented for the first time. The gases were sampled at the top of the sewage sludge digester using Tedlar bags, and were analysed using cryotrapping followed by gas chromatography coupled with inductively coupled mass spectrometry (GC-ICP-MS). The use of an ICP-MS as an element-specific detector gives sufficiently low detection limits for metals and was coupled to a packed column gas chromatograph. This method provides information about the speciation of volatile transition metals in contrast to previously used methods for the determination of Ni(CO)4 in gas samples. The element-specific detection of three different isotopes (m/z 58, 60, 62) and the correspondence of the samples' retention times with those of the standard provided convincing evidence that Ni(CO)4 is present in the fermentation gas. The concentrations found were in the sub-ppb level, which is at least one order of magnitude lower than the threshold level of 1 ppb (v/v). In addition, Mo(CO)6 and W(CO)6 were also measured in the sub-ppb range in contrast to the absence of Fe(CO)5. The stabilities of Ni(CO)4, Fe(CO)5, and Mo(CO)6 were tested in a carbon monoxide atmosphere. In the presence of distilled water, the following order of stability was found after 11 weeks: Fe(CO)5 < Ni(CO)4 < Mo(CO)6. In the presence of an aqueous solution containing nickel, molybdenum, tungsten and iron, however, only Fe(CO)5 was significantly decomposed (< 0.3% recovery); Ni(CO)4 and Mo(CO)6 were stable after 11 weeks. No W(CO)6 was formed. The low stability of Fe(CO)5 in the presence of water could be the reason why no volatile iron compound was found in sewage gas. This study showed that GC-ICP-MS can be employed to identify species-specific traces of metal carbonyls in process gases such as sewage gas.

Air Pollutants, Occupational↗

Genetic basis of hemophagocytic lymphohistiocytosis syndrome (Review).

The group of immune disorders which leads to the occurrence of hemophagocytic lymphohistiocytosis (HLH) syndrome presents a strange paradox in that patients with these conditions associate a dramatic immune response to infection with the failure to establish an effective immune response. During the last few years, significant progress was made in the characterization and the understanding of the molecular basis involved in these inherited immune disorders. The hemophagocytic lymphohistiocytosis syndrome which characterized the evolution of the Chediak-Higashi syndrome and the Griscelli disease results from defects affecting intracellular trafficking. A defective SH2 protein interacting with T lymphocyte intracellular signaling pathways is the cause of the X-linked lymphoproliferative disease, whereas at least three distinct genetic defects can lead to the familial hemophagocytic lymphohistiocytosis. The molecular characterization of these latter defects is in progress. This review summarizes the recent advances as well as their implications in the diagnosis and the understanding of the physiopathology of these disorders.

Animals↗

Sample preparation and storage can change arsenic speciation in human urine.

BACKGROUND: Stability of chemical speciation during sample handling and storage is a prerequisite to obtaining reliable results of trace element speciation analysis. There is no comprehensive information on the stability of common arsenic species, such as inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid, dimethylarsinic acid, and arsenobetaine, in human urine. METHODS: We compared the effects of the following storage conditions on the stability of these arsenic species: temperature (25, 4, and -20 degrees C), storage time (1, 2, 4, and 8 months), and the use of additives (HCl, sodium azide, benzoic acid, benzyltrimethylammonium chloride, and cetylpyridinium chloride). HPLC with both inductively coupled plasma mass spectrometry and hydride generation atomic fluorescence detection techniques were used for the speciation of arsenic. RESULTS: We found that all five of the arsenic species were stable for up to 2 months when urine samples were stored at 4 and -20 degrees C without any additives. For longer period of storage (4 and 8 months), the stability of arsenic species was dependent on urine matrices. Whereas the arsenic speciation in some urine samples was stable for the entire 8 months at both 4 and -20 degrees C, other urine samples stored under identical conditions showed substantial changes in the concentration of As(III), As(V), monomethylarsonic acid, and dimethylarsinic acid. The use of additives did not improve the stability of arsenic speciation in urine. The addition of 0.1 mol/L HCl (final concentration) to urine samples produced relative changes in inorganic As(III) and As(V) concentrations. CONCLUSIONS: Low temperature (4 and -20 degrees C) conditions are suitable for the storage of urine samples for up to 2 months. Untreated samples maintain their concentration of arsenic species, and additives have no particular benefit. Strong acidification is not appropriate for speciation analysis.

Arsenicals↗

Determination of organometallics in intra-oral air by LT-GC/ICP-MS.

Low temperature gas chromatography (LT-GC) coupled on-line with inductively coupled plasma mass spectrometry (ICP-MS) has been used to identify volatile metal and metalloid compounds in human breath. After cryogenic sampling, the gas sample has been separated without any clean-up by increasing the temperature (-100 to +200 degrees C). Simultaneous determination of 11 elements with ICP-MS was used for screening analysis. The detection limits of volatile compounds in intra-oral air are in the range of ng m(-3). Dimethyl selenium has been determined in each gas sample from six test persons in the range of 0.08 to 0.98 microg m(-3).

Journal Article↗

Koch et al. reply.

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Journal Article↗