Late Endosomal/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus.

To transfer the viral genome into the host cell cytoplasm, internalized influenza A virus (IAV) particles depend on the fusion of the IAV envelope with host endosomal membranes. The antiviral host interferon (IFN) response includes the upregulation of interferon-induced transmembrane protein 3 (IFITM3), which inhibits the release of the viral content into the cytosol. Although IFITM3 induction occurs concomitantly with late endosomal/lysosomal (LE/L) cholesterol accumulation, the functional significance of this process is not well understood.

Emerging functions as host cell factors - an encyclopedia of annexin-pathogen interactions.

Emerging infectious diseases and drug-resistant infectious agents call for the development of innovative antimicrobial strategies. With pathogenicity now considered to arise from the complex and bi-directional interplay between a microbe and the host, host cell factor targeting has emerged as a promising approach that might overcome the limitations of classical antimicrobial drug development and could open up novel and efficient therapeutic strategies. Interaction with and modulation of host cell membranes is a recurrent theme in the host-microbe relationship.

Annexin A6-balanced late endosomal cholesterol controls influenza A replication and propagation.

Unlabelled: Influenza is caused by influenza A virus (IAV), an enveloped, negative-stranded RNA virus that derives its envelope lipids from the host cell plasma membrane. Here, we examined the functional role of cellular cholesterol in the IAV infection cycle. We show that shifting of cellular cholesterol pools via the Ca(2+)-regulated membrane-binding protein annexin A6 (AnxA6) affects the infectivity of progeny virus particles.

Disruption of the annexin A1/S100A11 complex increases the migration and clonogenic growth by dysregulating epithelial growth factor (EGF) signaling.

Endocytosis of activated growth factor receptors regulates spatio-temporal cellular signaling. In the case of the EGF receptor, sorting into multivesicular bodies (MVBs) controls signal termination and subsequently leads to receptor degradation in lysosomes. Annexin A1, a Ca(2+)-regulated membrane binding protein often deregulated in human cancers, interacts with the EGF receptor and is phosphorylated by internalized EGF receptor on endosomes.

A method for the quantification of biomarkers of exposure to acrylonitrile and 1,3-butadiene in human urine by column-switching liquid chromatography-tandem mass spectrometry.

1,3-Butadiene and acrylonitrile are important industrial chemicals that have a high production volume and are ubiquitous environmental pollutants. The urinary mercapturic acids of 1,3-butadiene and acrylonitrile-N-acetyl-S-(3,4-dihydroxybutyl)cysteine (DHBMA) and MHBMA (an isomeric mixture of N-acetyl-S-((1-hydroxymethyl)-2-propenyl)cysteine and N-acetyl-S-((2-hydroxymethyl)-3-propenyl)cysteine) for the former and N-acetyl-S-2-cyanoethylcysteine (CEMA) for the latter-are specific biomarkers for the determination of individual internal exposure to these chemicals. We have developed and validated a fast, specific, and very sensitive method for the simultaneous determination of DHBMA, MHBMA, and CEMA in human urine using an automated multidimensional LC/MS/MS method that requires no additional sample preparation.

Simultaneous determination of mercapturic acids derived from ethylene oxide (HEMA), propylene oxide (2-HPMA), acrolein (3-HPMA), acrylamide (AAMA) and N,N-dimethylformamide (AMCC) in human urine using liquid chromatography/tandem mass spectrometry.

Mercapturic acids are highly important and specific biomarkers of exposure to carcinogenic substances in occupational and environmental medicine. We have developed and validated a reliable, specific and very sensitive method for the simultaneous determination of five mercapturic acids derived from several high-production chemicals used in industry, namely ethylene oxide, propylene oxide, acrylamide, acrolein and N,N-dimethylformamide. Analytes are enriched and cleaned up from urinary matrix by offline solid-phase extraction.

Fast determination of urinary S-phenylmercapturic acid (S-PMA) and S-benzylmercapturic acid (S-BMA) by column-switching liquid chromatography-tandem mass spectrometry.

Benzene and toluene are important industrial chemicals and ubiquitous environmental pollutants. The urinary mercapturic acids of benzene and toluene, S-phenylmercapturic acid (S-PMA) and S-benzylmercapturic acids (S-BMA) are specific biomarkers for the determination of low-level exposures. We have developed and validated a fast, specific and very sensitive method for the simultaneous determination of S-PMA and S-BMA in human urine using an automated multidimensional LC-MS-MS-method that requires no additional sample preparation.

Simultaneous determination of 3-nitrotyrosine, tyrosine, hydroxyproline and proline in exhaled breath condensate by hydrophilic interaction liquid chromatography/electrospray ionization tandem mass spectrometry.

The analysis of biomarkers from exhaled breath condensate (EBC) is a non-invasive but challenging method for the detection of pulmonary diseases. The amino acids L-proline (Pro) and l-tyrosine (Tyr) are precursors for two important metabolites, trans-L-4-hydroxyproline (trans-L-4-hydroxypyrrolidin-2-carboxylic acid, t-Hyp) and nitrotyrosine (NT). Whereas t-Hyp is supposed to be a biomarker for lung fibrosis, NT is a promising biomarker for inflammation in airway diseases.

Simultaneous determination of the advanced glycation end product N (epsilon)-carboxymethyllysine and its precursor, lysine, in exhaled breath condensate using isotope-dilution-hydrophilic-interaction liquid chromatography coupled to tandem mass spectrometry.

Analysis of biomarkers in exhaled breath condensate (EBC) is a non-invasive method for investigating the effects of different diseases or exposures, on the lungs and airways. N(epsilon)-carboxymethyllysine (CML) is an important biomarker of advanced glycation end products (AGEs). A method has been developed for simultaneous determination of CML and its precursor, the amino acid lysine, in exhaled breath condensate (EBC).

Determination of N epsilon-(carboxymethyl)lysine in exhaled breath condensate using isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry.

In order to identify new biomarkers for pulmonary diseases in exhaled breath condensate (EBC) it was the aim of this study to develop an analytical method for the identification and quantification of N epsilon-(carboxymethyl)lysine (CML) in EBC. As detection by liquid chromatography with positive electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) offers the advantage of structurally related detection with the necessary specificity required for the identification of a substance, it was the method chosen for the determination of the non-volatile compound. Specific mass transitions and comparison of retention times with standards under given conditions were used for the unequivocal identification of CML in EBC of healthy subjects.

Method optimization and validation for the simultaneous determination of arachidonic acid metabolites in exhaled breath condensate by liquid chromatography-electrospray ionization tandem mass spectrometry.

Background: Determinations of inflammatory markers in exhaled breath condensate were used to assess airway inflammation. The most applied method for this kind of determination is enzyme immunoassay. For research purposes to find new or to relate concrete biomarkers to different pulmonary diseases, a simultaneous determination of different inflammatory markers would be advantageous.

Sensitive and accurate analyses of free 3-nitrotyrosine in exhaled breath condensate by LC-MS/MS.

The quantitative determination of 3-nitro-l-tyrosine, a biological marker for inflammatory processes, in exhaled breath condensate (EBC) is described. The clean-up and preconcentration was performed by solid phase extraction (SPE). After liquid chromatography the specific detection was performed by tandem mass spectrometry using electron spray ionisation and selected reaction monitoring (SRM).

[Use of transmission and scanning electron microscopy in the cytological examination of the cerebrospinal fluid].

The authors carried out experiments with application of transmission and scanning electron microscopy in the examinations of the cell sediment of the cerebrospinal fluid obtained by membrane filtration. The method made possible ultrastructural examination of fluids with low cell count. The observed cells had natural shapes and well preserved morphological details.

[A method of membrane filtration of cells in the cerebrospinal fluid].

The authors discuss their assessment of the technique of membrane filtration of the cerebrospinal fluid based on an analysis of over 200 cytograms obtained using Milipore membrane filters. Filtration was done in Kistler's apparatus by the method of Kistler-Bischoff and the preparations were stained with hematoxylin and eosin. In the light of the obtained results and various envisaged possibilities of use the authors recommend this condensation technique as a method of choice in cytodiagnostic examinations of the cerebrospinal fluid.

[Clinical radicular symptoms in lumbosacral pain studies by radiculography with Dimer X].

Two hundred patients with low-back pain syndrome were studied. The results of neurological examination were compared with those of radiculography in these cases. It was found that although herniation of the nucleus pulposus at the L4-5 level is twice as frequent as at the L5-S1 level, radicular signs were demonstrated in 69% caused by injury to the S1 root and in 57% by injury to the L5 root.

[Diagnosis of expanding processes in the brain by means of brain scintigraphy and electroencephalography].

The purpose of the work was evaluation of the usefulness of brain scintiscanning and EEG in expanding lesions. The material included 144 patients, and primary tumours were found ultimately in 113 cases and secondary tumours in 31 cases. In 66 cases histological examinations were done.

[Stroke in the records of the Department of Neurology, Silesian Medical Academy in Katowice and Zabre as well as the Neurology Department of the 8th Municipal Hospital in Katowice in the years 1970-1974].

The authors analysed the clinical material of acute vascular diseases of the central nervous system treated at the Department of Neurology, Silesian Medical Academy and Neurological Department of the 8th Municipal Hospital providing in the years 1970-1974 medical care for the population of two greatest cities of the Upper Silesian Industrial Region in cases of sudden neurological diseases. Cerebrovascular strokes accounted for 14.7% of all hospitalized cases.

[Statistical analysis of mortality from stroke in hospitalized patients].

The authors analysed mortality from brain strokes in 1366 patients hospitalized at the Department of Neurology, Silesian Medical Academy in Katowice and Zabrze and in the 8th Municipal Hospital in Katowice in the years 1970--1974. The number of cases with lethal outcome was 437. The mortality was highest in cases of cerebral haemorrhages, particularly in women.

[Lioresal in the treatment of hemiplegia. Clinical and electromyographic evaluation. Preliminary report].

On the basis of an analysis of the clinical condition and electromyographic changes in 9 patients treated with Lioresal and 3 controls attention is called to the favourable effect of Lioresal in hemiparesis of cerebral origin. Lioresal was given in daily doses of 50 mg and no unfavourable side effects were observed. Reduction of muscular hypertonia and improvement of general motor activity was obtained.