Rapid thinning of the Late Pleistocene Patagonian Ice Sheet followed migration of the Southern Westerlies.

Here we present the first reconstruction of vertical ice-sheet profile changes from any of the Southern Hemisphere's mid-latitude Pleistocene ice sheets. We use cosmogenic radio-nuclide (CRN) exposure analysis to record the decay of the former Patagonian Ice Sheet (PIS) from the Last Glacial Maximum (LGM) and into the late glacial. Our samples, from mountains along an east-west transect to the east of the present North Patagonian Icefield (NPI), serve as 'dipsticks' that allow us to reconstruct past changes in ice-sheet thickness, and demonstrates that the former PIS remained extensive and close to its LGM extent in this region until ~19.0 ka. After this time rapid ice-sheet thinning, initiated at ~18.1 ka, saw ice at or near its present dimension by 15.5 ka. We argue this rapid thinning was triggered by a combination of the rapid southward migration of the precipitation bearing Southern Hemisphere (SH) westerlies and regional warming.

Percentile curves for skinfold thickness in 7- to 14-year-old children and adolescents from Jena, Germany.

OBJECTIVE: To present age- and sex-specific percentile curves for triceps and subscapular skinfold thickness, and to investigate long-term changes in skinfold thickness in children. SUBJECTS/METHODS: A cross-sectional study of children and adolescents was conducted in Jena/Germany in 2005/2006. The sample consisted of 2132 children (1018 girls and 1114 boys) aged 7-14 years and equated to the anthropometric characteristics of the German sample included in the reference values for body mass index (BMI). Height, weight and triceps and subscapular skinfold measurements were obtained using standardized methods. Smoothed percentile curves for triceps and subscapular skinfold thickness were derived by the LMS method. Data were compared with historical data of Jena schoolchildren from 1975. RESULTS: In both sexes, skinfold thickness increased between 7 and 14 years of age in a sex-specific pattern, with generally higher median values for triceps and subscapular skinfold in girls than boys. A comparison with skinfold thickness measured in Jena schoolchildren three decades ago showed a significant increase in subcutaneous fat. The changes in the lower range (below the tenth percentile) of the distribution exceed those in the upper range (above the 90th percentile) for both triceps and subscapular skinfold in both sexes. Furthermore, this gain in subcutaneous fat mainly occurred in underweight and normal-weight subjects, whereas skinfold thickness remained nearly unchanged in overweight subjects. CONCLUSIONS: The up-to-date percentile curves for skinfold thickness provide a basis for monitoring of individuals and evaluation of long-term trends in German children and adolescents. The changes in skinfold thickness indicate an unfavourable increase in adiposity, as well as an unfavourable change in the relationship between BMI and body fat in children and adolescents over time.

Validity of body mass index and waist circumference to detect excess fat mass in children aged 7-14 years.

BACKGROUND/OBJECTIVES: To evaluate the screening performance of body mass index (BMI) and waist circumference (WC) for excess adiposity. In addition, the diagnostic accuracy of cutoffs from different international and national reference systems based on BMI and WC was investigated. SUBJECTS/METHODS: Data from 2132 Jena children aged 7-14 years conducted in 2005/2006 were analyzed. Receiver operating characteristic (ROC) curves were constructed to assess BMI and WC, as screening measures for excess adiposity (derived from skinfolds). Sensitivity, specificity and positive predictive values (PPVs) were calculated for two BMI-based classification systems (IOTF and German reference) and sample-based WC cutoffs. RESULTS: The BMI as well as the WC performed well in detecting excess fat mass, indicated by areas under the ROC curve (AUC) close to 1.0, with slightly greater AUCs for BMI than for WC in both sexes. The specificity of all reference systems was high for both sexes (95 to 98%). However, their sensitivities were low (53-67% in boys; 51-67% in girls). PPV were higher for the German reference and the sample-based WC cutoffs than for the IOTF reference, and higher in girls than in boys. CONCLUSIONS: The setting in which the reference system should be used is important for the selection of the reference system. The results support the use of the BMI-based references for monitoring in epidemiological studies. The sample-based cutoffs for WC should be refined for clinical use on national level.

[Experimental studies of long-term effect of a detergent disinfecting for surface on a strain of Escherichia coli]. / Etudes expérimentales de l'effet rémanent d'un détergent désinfectant pour surfaces sur une souche d'Escherichia coli.

We offer three complementary, original methods and reproducibles to study the antibacterial and long-term effect of a detergent disinfecting for surfaces commercialized lately in France. Long-term activity noticed-effect is compared with that of other products. We first study the curves of growth of a strain of Escherichia coli put in presence with the surface of the wells of a microplate beforehand and for several days (from D-10 to D0), coated with disinfecting detergents. Another method consisted on surfaces firstly treated from D-10 to D0 by the one or the other product to be tested, which are artificially contaminated in a standardized manner by a velvet footprint with a suspension of E. coli. The surviving microbes are counted after transfer on a Rodac plate. Finally, doorhandles are cleaned and disinfected with the product. The natural bacterial recolonization doorhandles is studied by daily Rodac plate within a week. These studies allow to prove that Bacoban introduces a bactericidal activity on E. coli with an long-term effect for at least 10 days. The most competitive products have a bacteriostatic effect during nine to 10 days, but bactericidal effect only during two days. This bactericidal long-term effect may be particularly interesting in hospital hygiene for the biocleaning of the most manipulated surfaces and should restrict the role of bacterial reservoir of certain surfaces participating in care or near of the patients.

Phlebotomine sandflies (Diptera: Psychodidae) of the genus Sergentomyia in Marrakech region, Morocco.

We reported the results of an entomological investigation in Marrakech area, in the aim to study the present Sergentomyia species composition. One hundred thirty seven sandflies were collected by sticky papers and they comprised three sub-genera: Parrotomyia (43.1%), Sergentomyia (36.5%), and Grassomyia (20.4%). Four species were identified; Sergentomyia (Parrotomyia) africana Newstead (43.1%) followed by S. (Grassomyia) dreyfussi Parrot, S. (Sergentomyia) fallax Parrot, and S. (S.) minuta Rondani accounted for 20.4%, 19.7%, and 16.8%, respectively. Ecological study subdivides these species into rural species (S. africana and S. dreyfussi) and ubiquitous species (S. minuta and S. fallax) which were collected in both urban and rural areas. Enzymatic analysis identified three monomorphic loci (alphaGPDH, ICD, and ME) and six polymorphic loci (PGI, HK, FUM, MDH2, 6PGD, and ACO) in the four species. At FUM and ACO loci, some alleles appeared to be fixed in each species. Morphological (counts of cibarial teeth) and isoenzymatic analysis of wild populations of S. minuta parroti from Morocco and of S. minuta minuta from continental Europe (France, Spain, and Portugal) was carried out. Morphological results showed significant differences between France and Portugal populations and south Spain populations. In contrast, there was no significant difference between northern and southern Moroccan populations. Genetic variability showed a separation between northern and southern European populations and S. minuta from Andalusia clustered with Moroccan populations.

Morphological and isoenzymatic differentiation of Phlebotomus perniciosus and Phlebotomus longicuspis (Diptera: Psychodidae) in Southern Morocco.

Morphological and enzymatic characterization of Phlebotomus perniciosus and Phlebotomus longicuspis in Morocco is reported. Twenty-nine localities in central and southern of Morocco were sampled and compared with three localities from the Rif (northern Morocco). For morphological study, sand flies were collected by sticky-paper traps. For males, the morphology of the copulatory valves (aedeagi) was examined and the number of coxite hairs was recorded. For isoenzyme analyses, specimens were collected in CDC light traps and immediately conserved at -80 degrees C. P. perniciosus samples from the south of Morocco, up to 150 km from Marrakech, showed single-pointed aedeagi curved at their apices, indistinguishable from the atypical morph of P. perniciosus, previously described in northern Morocco. Twelve enzyme systems were tested and the qualitative analysis of zymogram profiles revealed eight polymorphic loci (glucosephosphate isomerase (GPI), phosphoglucomutase (PGM), hexokinase (HK), fumarate hydratase (FUM), malate dehydrogenase 1 (MDH1), malate dehydrogenase 2 (MDH2), 6 phosphogluconate dehydrogenase (6PGD) and aconitase (ACO)). Enzyme loci showed fixed alleles diagnostic for P. perniciosus (aconitase) and P. longicuspis (aconitase and hexokinase).

Effect of glucocorticoids on stem cell factor expression in human asthmatic bronchi.

BACKGROUND: Stem cell factor (SCF) is a major mast cell growth factor promoting differentiation, chemotaxis as well as inhibition of apoptosis of mast cells. Regulation of SCF expression by glucocorticoids has not yet been reported in human asthmatic bronchi. OBJECTIVE: To evaluate SCF mRNA and protein expression in biopsy specimen and bronchoalveolar lavage fluid, respectively, and to determine the mast cell numbers in biopsy sections from control and asthmatic subjects treated or not with glucocorticoids. METHODS: Volunteers were recruited out of pollen season. Asthmatic patients were allergic to common allergen extracts including grass and tree pollen, cat, dog or mite; three volunteers had non-allergic asthma. Mast cell numbers were counted after anti-human tryptase immunolabelling. SCF mRNA was quantified by real-time fluorescent PCR (LightCycler) after reverse transcription, and SCF protein was measured by ELISA. RESULTS: Asthmatic patients not treated with glucocorticoids showed a 5.8-, 1.8- and 3.1-fold significant increase in SCF mRNA, protein levels and mast cell numbers, respectively, compared with healthy volunteers of the control group (7.8 and 1.3 pg/mug SCF mRNA/GAPDH; 99.8+/-11.5 and 56.0+/-11.0 pg/mL SCF protein; 103+/-21 and 33+/-8 mast cells/mm(2), respectively; P<0.05). In asthmatic patients treated with glucocorticoids, a significant decrease of SCF mRNA, protein levels and mast cell numbers was observed as compared with untreated asthmatic patients (1.1 pg/microg mRNA; 62.0+/-10.3 pg/mL SCF protein and 39+/-13 mast cells/mm(2); P<0.05), reaching levels comparable to those of the control group. CONCLUSION: Our study shows that SCF is expressed in the bronchus in humans in vivo. This expression is increased in asthma, and is parallel to the increased mast cell numbers in the airways. Both increases were normalized in glucocorticoid-treated patients, strongly suggesting an involvement of SCF in the mast cell-associated asthmatic disease.

[Pharmacists' role in the management of asthma: a survey of 120 pharmacists in Bas-Rhin]. / Prise en charge de l'asthme à l'officine: enquête auprès de 120 pharmaciens du Bas-Rhin.

INTRODUCTION: The pharmacist plays an essential role in the management of the asthmatic patients on account of their frequent visits to the pharmacy to obtain their medication. METHODS: In order to evaluate the practice and knowledge of asthma among the pharmacists of the department of Bas-Rhin, 120 pharmacists were selected at random to reply to a standardised questionnaire. RESULTS: The 86 pharmacists who replied to the questionnaire had a good general understanding of asthma and its treatment. However, only 26.4% knew all the criteria of the severity of an attack of asthma. Among the 57 pharmacists who gave a demonstration of the use of inhaler devices, 16.3% showed all the steps in the use of a metered dose aerosol. These results are comparable to those of non-specialist doctors and nurses in whom poor techniques were found in 63-100% and 65-96% respectively. The mean scores of the pharmacists were 10.5/12 (+/- 1.2) steps for metered dose aerosols, 10.4/11 (+/- 1.0) for the Tubuhaler, 9.3/12 (+/- 1.7) for the Autohaler and 8.1/9 (+/- 0.9) for the Volumatic spacer. The asthmatic patient's main expectation of the pharmacist concerned the use of the prescribed systems (87.2%), underlining the lack of information received by the patient at the time of prescription. CONCLUSIONS: An improvement in the knowledge of the signs of severity of asthma and the use of inhaled devices could usefully be one of the objectives in the training of a dispensing pharmacist.

[Influence of pyridoxal phosphate in measuring aminotransferases activities in patients with viral hepatitis]. / Effet du phosphate de pyridoxal dans la mesure des activités aminotransférases chez les patients avec hépatite virale.

Effect of a pyridoxal phosphate (PP) supplementation of reagents used for ALT and AST measurement was studied in serum of 20 patients suffering from viral hepatitis. Measurements of enzyme activities were carried out at 37 degrees C, using an automate (AU 600, Olympus). Significant differences (p < 0.0001) were observed both for ALT and AST, meanwhile they were more marked for ALT than for AST. This difference was associated with a strong interindividual variability regarding PP activation effect on ALT. In conclusion, aminotransferase measurements should be carried out with a reagent supplemented with PP, when the enzyme activity is used to evaluate a cytolysis. The same recommendation applies when ALT results are integrated into various combinations developed for the evaluation of liver status.

Nasal effect of cetirizine and loratadine at 24 hours in patients with allergic rhinitis.

Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P < 0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.

Onset of action in the nasal antihistaminic effect of cetirizine and loratadine in patients with allergic rhinitis.

Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.

The plasma-membrane internalization and recycling is enhanced in macrophages upon activation with gamma-interferon and lipopolysaccharide; a study using the fluorescent probe trimethylaminodiphenylhexatriene.

The lipophilic fluorescent probe trimethylaminodiphenylhexatriene (TMA-DPH), previously used as a plasma membrane marker in membrane fluidity and exocytosis studies, was shown, to monitor the plasma-membrane internalization-recycling shuttle movement in cells. Using this approach we present here kinetic and dose-response data, which give evidence that the plasma membrane flow is enhanced in bone marrow macrophages from various mouse strains, upon in vitro activation with gamma interferon (IFN-gamma) or bacterial lipopolysaccharide (LPS), within physiological dose ranges. The effect studied evolved in line with the usual development kinetics of macrophage activation. Complementary assays on membrane fluidity, surface charge density and membrane surface indicated no related changes. From these experiments it is concluded that the observed enhancement of the plasma membrane traffic does not originate from specific limited membrane modifications, but is merely a particular feature of the overall macrophage activation.

Soybean phosphatidylcholine vesicles containing plant sterols: a fluorescence anisotropy study.

The typical plant sterols (sitosterol, stigmasterol and campesterol) were compared with respect to their ability to regulate membrane fluidity of soybean phosphatidylcholine (PC) vesicles. Fluidity changes were monitored by the steady-state fluorescence anisotropy with 1,6-diphenyl-1,3,5-hexatriene as a probe and assigned to a measure of the acyl chain orientational order. Sitosterol and campesterol appear to be the most suitable sterols in ordering the acyl chains of soybean lecithin bilayers, even more efficient than cholesterol, the standard of reference for sterol effects on membranes, suggesting that they play a significant role in the regulation of plant membrane properties. Stigmasterol is shown to be much less active. Cycloartenol, a biosynthetic precursor of plant sterols, increases the acyl chain order with the same efficiency as cholesterol. We also investigated the effects of two unusual sterols, 24-methylpollinastanol and 14 alpha,24-dimethylcholest-8-en-3 beta-ol, which were shown to accumulate in plants treated with fungicides belonging to two important classes, N-substituted morpholines and triazoles, respectively. These two sterols exhibit a behavior very similar to that of stigmasterol. The results are discussed in terms of sterol effects on the molecular packing of soybean PC bilayers.

Bimane- and acrylodan-labeled S100 proteins. Role of cysteines-85 alpha and -84 beta in the conformation and calcium binding properties of S100 alpha alpha and S100b (beta beta) proteins.

Bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) protein dimers were labeled with the sulfydryl-specific fluorescent probes monobromo(trimethylammonio)bimane (bimane) and 6-acryloyl-2-(dimethylamino)naphthalene (acrylodan) at cysteines-85 alpha and -84 beta. The conformation and fluorescence properties of the S100 proteins derived were studied by means of anion-exchange chromatography on a Mono Q column using a fast protein chromatography system and fluorescence intensity, maximum emission wavelength, and polarization measurements. Spectroscopic studies on the intrinsic absorption and fluorescence properties of S100 alpha alpha and S100b proteins chemically modified on cysteines-85 alpha and -84 beta with iodoacetamide completed this study. Several arguments suggest that the alkylated S100 proteins undergo conformational changes that are mainly characterized by the destabilization of the quaternary protein structure, which provokes a slow dimer-monomer equilibrium at high protein concentrations and induces total subunit dissociation at low ones. Calcium binding studies on bimane-S100 alpha alpha and -S100b proteins showed that alkylated proteins had a much higher calcium binding affinity than native protein and that the antagonistic effect of KCl on calcium binding was much less pronounced. These results confirmed our previous observations that the affinities of calcium binding sites II alpha and II beta in S100 proteins are highly dependent on protein conformation [Baudier, J., & Gerard, D. (1986) J. Biol. Chem. 261, 8204-8212].

Ions binding to S100 proteins. I. Calcium- and zinc-binding properties of bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) protein: Zn2+ regulates Ca2+ binding on S100b protein.

Flow dialysis measurements of calcium binding to bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) proteins in 20 mM Tris-HCl buffer at pH 7.5 and 8.3 revealed that S100 proteins bind specifically 4 Ca2+ eq/mol of protein dimer. The specific calcium-binding sites had, therefore, been assigned to typical amino acid sequences on the alpha and beta subunit. The protein affinity for calcium is much lower in the presence of magnesium and potassium. Potassium strongly antagonizes calcium binding on two calcium-binding sites responsible for most of the Ca2+-induced conformational changes on S100 proteins (probably site II alpha and site II beta). Zinc-binding studies in the absence of divalent cations revealed eight zinc-binding sites/mol of S100b protein dimer that we assumed to correspond to 4 zinc-binding sites/beta subunit. Zinc binding to S100b studied with UV spectroscopy methods showed that the occupation of the four higher affinity sites and the four lower affinity sites on the protein dimer were responsible for different conformational changes in S100b structure. Zinc binding on the higher affinity sites regulates calcium binding to S100b by increasing the protein affinity for calcium and decreasing the antagonistic effect of potassium on calcium binding. Zinc-binding studies on S100a and S100 alpha alpha protein showed that the Trp-containing S100 proteins bind zinc more weakly than S100b protein. Calcium-binding studies on zinc-bound S100a proved that calcium- and zinc-binding sites were distinct although there was no increase in zinc-bound S100a affinity for calcium, as in S100b protein. Finally we provide evidence that discrepancies between previously published results on the optical properties of S100b protein probably result from oxidation of the sulfhydryl groups in the protein.

Purification, calcium-binding properties, and conformational studies on a 28-kDa cholecalcin-like protein from bovine brain.

A large-scale preparation method for bovine brain 28-kDa cholecalcin-like protein is described. Flow dialysis binding studies revealed that the protein binds at least 3 mol of Ca2+/mol of protein. The protein undergoes conformational changes on binding calcium as shown by UV differential absorption spectroscopy, near and far UV circular dichroism, and intrinsic fluorescence. Circular dichroism (CD) studies in the far UV indicate an apparent increase in helical content in the presence of Ca2+. The effect of calcium on the protein structure is nearly maximum for 1 Ca2+ bound/protein molecule. UV differential absorption studies on the binding of the Ca2+ agonist Tb3+ and Tb3+ luminescence induced by energy Trp----Tb3+ transfer indicate that Tb3+ binds to two higher affinity Ca2+-binding sites. These sites are probably very close to the single Trp residue. Analysis of the fluorescence parameters of the single tryptophan residue in the apoprotein and its accessibility to ionic and neutral quenchers suggests that this residue is located in a highly hydrophobic domain on the protein surface.

Purification, characterization and ion binding properties of human brain S100b protein.

Human brain S100b (beta beta) protein was purified using zinc-dependent affinity chromatography on phenyl-Sepharose. The calcium- and zinc-binding properties of the protein were studied by flow dialysis technique and the protein conformation both in the metal-free form and in the presence of Ca2+ or Zn2+ was investigated with ultraviolet spectroscopy, sulfhydryl reactivity and interaction with a hydrophobic fluorescence probe 6-(p-toluidino)naphthalene-2-sulfonic acid (TNS). Flow dialysis measurements of Ca2+ binding to human brain S100b (beta beta) protein revealed six Ca2+-binding sites which we assumed to represent three for each beta monomer, characterized by the macroscopic association constants K1 = 0.44 X 10(5) M-1; K2 = 0.1 X 10(5) M-1 and K3 = 0.08 X 10(5) M-1. In the presence of 120 mM KCl, the affinity of the protein for calcium is drastically reduced. Zinc-binding studies on human S100b protein showed that the protein bound two zinc ions per beta monomer, with macroscopic constants K1 = 4.47 X 10(7) M-1 and K2 = 0.1 X 10(7) M-1. Most of the Zn2+-induced conformational changes occurred after the binding of two zinc ions per mole of S100b protein. These results differ significantly from those for bovine protein and cast doubt on the conservation of the S100 structure during evolution. When calcium binding was studied in the presence of zinc, we noted an increase in the affinity of the protein for calcium, K1 = 4.4 X 10(5) M-1; K2 = 0.57 X 10(5) M-1; K3 = 0.023 X 10(5) M-1. These results indicated that the Ca2+- and Zn2+-binding sites on S100b protein are different and suggest that Zn2+ may regulate Ca2+ binding by increasing the affinity of the protein for calcium.