Psychophysical studies of the itch sensation and itchy skin ("alloknesis") produced by intracutaneous injection of histamine.

Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections of histamine or papain into the volar forearm. Histamine and papain were given in doses of 0.1, 1, or 10 micrograms in 10 microliters of saline. The effects of the depth of injection and of skin temperature on the latency, magnitude, and duration of itch were examined. Also, dose-response functions were obtained for the area of alloknesis produced by intracutaneous injections of histamine. Finally, the neural mechanisms underlying the spread of alloknesis were investigated via local anesthesia of the skin. Intracutaneous and subcutaneous injections of histamine, but not papain, produced a sensation of itch without pain. The latency of itch was shorter after an intracutanous than after a subcutaneous injection of histamine. The mean latencies of itch produced by a 1-microgram dose were 9.5 and 23.0 sec for intracutaneous and subcutaneous injections, respectively. No differences were observed in the magnitude or duration of itch. Similarly, the latency of itch was increased when the skin temperature at injection site was lowered to 15 degrees C, whereas the magnitude and duration of itch were unaffected. Intracutaneous and subcutaneous injections of histamine produced similar areas of alloknesis. However, the magnitude and duration of alloknesis were dependent on dose. The mean maximum areas of alloknesis produced by intracutaneous injections of 0.1, 1, and 10 micrograms of histamine were 28.3, 47.2, and 43.8 cm2, respectively. Alloknesis was present at 2 min after injection, increased to a maximum area without 10 min, and then gradually decreased during the next 25-40 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

3D structure of bovine pancreatic ribonuclease A in aqueous solution: An approach to tertiary structure determination from a small basis of1H NMR NOE correlations

Summary A method is proposed to generate initial structures in cases where the distance geometry method may fail, such as when the set of¹H NMR NOE-based distance constraints is small in relation to the size of the protein. The method introduces an initial correlation between the and backbone angles (based on empirical observations) which is relaxed in later stages of the calculation. The obtained initial structures are refined by well-established methods of energy minimization and restrained molecular dynamics. The method is applied to determine the solution structure of Ribonuclease A (124 residues) from a NOE basis consisting of 467 NOE cross-correlations (97 intra-residue, 206 sequential, 23 medium-range and 141 long-range) obtained at 360 MHz. The global shape and backbone overall fold of the eight final refined structures are close to those shown by the crystal structure. A meaningful difference in the positioning of the catalytically important His¹¹⁹ side chain in the solution and crystal structures has been detected.     

Use of synthetic resin cases for the scanning electron microscopic study of the kidney tubule system

Aim of our present work was to investigate a new method to study the three-dimensional arrangement, the length and the diameter of the different parts of the renal tubules. The ureter was cannulated after blocking the urinary flow with a binding of the ureter itself at its intermediate third, and injected in it against flow a synthetic resin (Mercox) normally used for vascular corrosion casts. It was demonstrated that the binding maintained only for 24 hours is adequate for morphological studies of the urinary tracts from papillar ducts until the Henle's loop. On the contrary the binding maintained for 7 days induced marked changes in the tubular architecture similar to the first anatomo-pathological changes of the nephrosclerosis following a chronic obstructive nephropathy.     

Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells II. Test validation and interpretation

The L5178Y Mouse Lymphoma TK assay was studied extensively to determine if this mammalian cell assay for gene mutations at the thymidine kinase (TK) locus could provide valid, interpretable determinations of mutagenic potential, and whether this information is of value in the safety evaluation of chemicals. We first determined that test-derived TFT^R mutants were phenotypically stable, possessing little or no thymidine kinase activity as measured by labeled thymidine uptake, but demonstrating 100% cross resistance to bromodeoxyuridine. Common solvent vehicles such as acetone, dimethylsulfoxide and ethanol were shown to produce little cytotoxicity and no mutagenic activity when present at 1% levels. Out of a total of 10 noncarcinogens tested, all were negative when results were analyzed by a 2-sample log_et test on control and treated mutant count means. Of the 13 putative animal carcinogens tested, 10 were positive, 2 were negative (auramine O and sodium phenobarbital), and 1 showed sporadic activity (hydrazine sulfate) in the TK assay on the basis of test-derived t statistics. 2 compounds, 1,2-epoxybutane and ICR 191, which have been described as Ames positive non-carcinogens, were also positive in the TK assay. Although this sampling of a total of 29 compounds is insufficient for precise estimations of expected false-positive or false-negative frequencies, these data indicate the TK assay can be expected to detect a majority of carcinogens as mutagens including some missed by more established point-mutation assays.     

Révision systématiquedu genre Steginoporella smitt, 1873 (Bryozoa Cheilostomata)

Systematic revision of the genus Steginoporella: until now about eighty species were described. Only twenty recent species and thirty-four fossil ones are maintained. Several species and subspecies are new.The main interest of this revision is to establish a biostratigraphical scale: the settlement of this scale is based on the known stratigraphical distribution and on an attempt of phylogeny.The second advantage is ecological: all recent species live in marine tropical environment. The Steginoporella are good paleoecological indicators.At last, the establishment of a paleobiogeography, even incomplete and not definitive, allows to understand more easily recent distribution of Steginoporella connected with the great events of earth evolution.     

13C NMR investigations on Npi-[13C1]carboxymethyl-histidine-119 ribonuclease.

The ribonuclease A derivative Npi-[13C1]carboxymethyl-histine-119 ribonuclease prepared by using [13C1]bromoacetate as alkylating reagent has been investigated with high resolution 13C NMR spectroscopy. In the 13C NMR spectra two carbon resonances of relatively high intensity appear which can be assigned to carboxyl groups attached to His-119 and Met-30, their intensity ratio being 10 : 1. The pH dependence of the carbon resonance of the carboxy-methyl group bound to the Npi of His-119 differs in the absence and presence of Cyd-2'-P, thus indicating that the catalytically inactive derivative does bind nucleotides. A mechanism of the alkylation reaction at pH 5.6 is proposed in which the epsilon-amino group of Lys-41 acts as the binding site for the carboxyl group of bromoacetate pushing the bromomethylene group towards the Npi of His-119 or the Ntau of His-12.     

E-Readers and Visual Fatigue

The mass digitization of books is changing the way information is created, disseminated and displayed. Electronic book readers (e-readers) generally refer to two main display technologies: the electronic ink (E-ink) and the liquid crystal display (LCD). Both technologies have advantages and disadvantages, but the question whether one or the other triggers less visual fatigue is still open. The aim of the present research was to study the effects of the display technology on visual fatigue. To this end, participants performed a longitudinal study in which two last generation e-readers (LCD, E-ink) and paper book were tested in three different prolonged reading sessions separated by - on average - ten days. Results from both objective (Blinks per second) and subjective (Visual Fatigue Scale) measures suggested that reading on the LCD (Kindle Fire HD) triggers higher visual fatigue with respect to both the E-ink (Kindle Paperwhite) and the paper book. The absence of differences between E-ink and paper suggests that, concerning visual fatigue, the E-ink is indeed very similar to the paper.     

E-cadherin deregulation in breast cancer

E-cadherin protein (CDH1 gene) integrity is fundamental to the process of epithelial polarization and differentiation. Deregulation of the E-cadherin function plays a crucial role in breast cancer metastases, with worse prognosis and shorter overall survival. In this narrative review, we describe the inactivating mechanisms underlying CDH1 gene activity and its possible translation to clinical practice as a prognostic biomarker and as a potential targeted therapy.