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Aims:to confirm the diagnosis of 21-hydroxylase deficiency (21-OHD) by the analysis of CYP21A2 gene in infants with clinical and/or biochemical features of 21-OHD in order to clarify which patients to submit to genetic analysis; to analyze the genotype-phenotype concordance in these infants. Subjects and methods:We studied 25 children with clinical and/or biochemical features of 21-OHD. All of them and their parents were submitted to genetic analysis of CYP21A2. Patients were classified in 3 groups according to mutations’ severity: severe (group A), moderate (group B) or mild (group C). Results:CYP21A2 gene mutations were found in 17 children. Whereas all infants of groups A and B presented a classical form of 21-OHD, children of group C had a non-classical form of 21-OHD. Four infants resulted heterozygotes and 4 children were wild-type. A girl clinically presenting a non-classical form of 21-OHD resulted compound heterozygote with one of the mutations not described in literature (R25W) and whose residual enzymatic activity is not already known. All affected children presented a 17-OHP level after ACTH stimulation greater than 100 nmol/l. We found an optimal concordance between 17-OHP levels after ACTH test and genotype. Conclusions:CYP21A2 analysis permitted to confirm the diagnosis of 21-OHD in 68% of our children. To improve this percentage we suggest to perform the CYP21A2 analysis only when 17-OHP after ACTH test is greater than 100 nmol/l. Moreover, we found an optimal genotype-phenotype concordance in the 21-OHD patients.

Abstract.: The interaction of a Grand Unification Magnetic Monopole with a nucleon can lead to a barion-number violating process in which the nucleon decays into a lepton and one or more mesons (catalysis of nucleon decay). In this paper we report an experimental study of the effects of a catalysis process in the MACRO detector. Using a dedicated analysis we obtain new magnetic monopole (MM) flux upper limits at the level of for , based on the search for catalysis events in the MACRO data. We also analyze the dependence of the MM flux limit on the catalysis cross section.

Muon energy measurement represents an important issue for any experiment addressing neutrino-induced up-going muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDCs included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for E μ <40 GeV . The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data.

The angular distribution of upward-going muons produced by atmospheric neutrinos in the rock below the MACRO detector shows anomalies in good agreement with two flavor νμ→ντoscillations with maximum mixing and Δm2around 0.0024 eV2. Exploiting the dependence of magnitude of the matter effect on oscillation channel, and using a set of 809 upward-going muons observed in MACRO, we show that the two flavor νμ→νsoscillation is disfavored with 99% C.L. with respect to νμ→ντ.

The edible seeds of the quinoa plant contain small quantities of alcohol-soluble protein which, after peptic-tryptic digestion, are unable to agglutinate K562(s) cells. When separated by affinity chromatography on sepharose-6B coupled with mannan, peptic-tryptic digest separated in two fractions. Fraction B peptides (about 1% of total protein) were shown to agglutinate K562(s) cells at a very low concentration, whereas peptides in fraction A and in the mixed fraction A+B were inactive, suggesting that fraction A contains protective peptides that interfere with the agglutinating activity of toxic peptides in fraction B.

Background: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH2-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has been investigated. Methods: Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought. Results: Peptides 31-55 and 31-43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25-positive cells. Conclusions: Our results suggest that 31-43 and 44-55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.

We present a study of the correlations in the arrival times of about 1016single and multiple muons detected by the first two MACRO supermodules. The time correlations, from milliseconds to several hundrends of seconds, have been analyzed in terms of the random distribution, with which they are consistent. An analysis of the arrival times (up to 180 ns) of the muons from the same multimuon event is also given.

ABSTRACT: Subfraction 2R of fraction 9 from a peptic-tryptic-pancreatic digest of wheat gliadin is known to be toxic in vivo to celiac patients. We have found that fractions 9 and 2R inhibit the in vitro development of fetal rat intestine and the increase of enterocyte height occurring in organ culture of atrophic celiac mucosa (0.1–0.5 mg/ml medium). Other peptide fractions of the gliadin digest are devoid of such in vitro effects. Subfraction 2R, after incubation with morphologically normal small intestinal mucosa of celiacs in remission and ultrafiltration, was still very active in both culture systems at low concentration (0.1 mg/ml); on the contrary, subfraction 2R was inactivated after incubation with normal mucosa. These results are compatible with the hypothesis that there is a mucosal defect in handling gliadin peptides in celiac disease, and suggest that there is either a primary (or secondary) enzyme deficiency or some other mechanism operating in the intestinal mucosa of celiac patients in remission.

Peptic-tryptic-Cotazym (PTC) digests were obtained, simulating in vivoprotein digestion, from rice, maize, rye, oats, barley, and sorghum prolamines and tested on small intestine cultures from rat fetus. The PTC digests of the prolamine fractions from rice and maize, even when tested at a concentration as high as 0.5 mg/ml, did not affect in vitrodifferentiation and maturation of fetal rat jejunum that took place in vitroin a way comparable to what happens in vivo. On the contrary, the PTC digests of prolamines from rye, oats, barley, and sorghum were very active in slowing down in vitro development of fetal rat intestine. These results further strengthen earlier findings and all together show that there is a strong correlation between toxicity results of cereal and/or cereal components assessed with clinical trials or in vitrosystems based on bioptic specimens of intestinal mucosa from celiac patients and with the culture of rat fetal intestine. Therefore, the rat fetal intestine culture is considered to be an adequate model for screening and investigating cereal peptides which are toxic for the celiac small intestinal mucosa.

Peptic-tryptic-cotazym and peptic-tryptic digests wore obtained, simulating in vivo protein digestion, from pure “bread” wheat gliadins and from rye, barley, and oats prolamine and tested on small intestine cultures from fetal rats. When tested at a concentration of 0.1 mg of peptides/ml of culture medium the peptic-tryptic-cotazym and peptic-tryptic digests of gliadin and prolamines were very active in slowing in vitro development of fetal rat intestine and in increasing the occurrence and severity of degenerative changes. The ability of some sugars to interfere with inhibition of fetal intestinal morphogenesis induced by these peptides was also tested. Mannan at a concentration of 0.1 mM was effective in allowing intestinal morphogenesis to take place in the presence of prolamine peptic-tryptic-cotazym and prolamine peptic-tryptic digests of the four toxic cereals. Some oligomers of N-acetylglucosamine were also effective in blocking the inhibitory effect of “bread” wheat gliadin peptides. These data are compatible with the hypothesis that some sugars may exert a protective effect on the toxic activity of cereal prolamin peptides on the human celiac intestine.

This paper describes work that shows that the PTC digest of gliadins extracted from hexaploid wheat flour have the same toxic activity of the PTC digest of gliadins extracted from hexaploid wheat gluten. Moreover, not all wheat species apparently contain the toxic components, thus suggesting that durum wheat foods may present, as compared to soft wheat foods, a lower risk for human health under particular circumstances. Similar considerations seem to apply to other cereal genera that seem to differ with respect to the presence and/or content of toxic peptides. Further experiments to test such a working hypothesis are now being made.

This paper describes work that shows that the PTC digest of gliadins extracted from hexaploid wheat flour have the same toxic activity of the PTC digest of gliadins extracted from hexaploid wheat gluten. Moreover, not all wheat species apparently contain the toxic components, thus suggesting that durum wheat foods may present, as compared to soft wheat foods, a lower risk for human health under particular circumstances. Similar considerations seem to apply to other cereal genera that seem to differ with respect to the presence and/or content of toxic peptides. Further experiments to test such a working hypothesis are now being made.

Peptic-tryptic-cotazym (PTC) digests were obtained, simulating in vivoprotein digestion, from albumin, globulin, gliadin and glutenin preparations from hexapiod (bread) wheat as well as from diploid (monococcum) and tetraploid (durum) wheat gliadins. The digest from breadwheat gliadins reversibly inhibited in vitrodevelopment and morphogenesis of small intestine from 17-day-old rat fetuses, whereas all the other digests (obtained both from nongliadin fractions and from gliadins from other wheat species) were inactive.

ABSTRACT. Peptic-tryptic-cotazym and peptic-tryptic digests wore obtained, simulating in vivo protein digestion, from pure “bread” wheat gliadins and from rye, barley, and oats prolamine and tested on small intestine cultures from fetal rats. When tested at a concentration of 0.1 mg of peptides/ml of culture medium the peptic-tryptic-cotazym and peptic-tryptic digests of gliadin and prolamines were very active in slowing in vitro development of fetal rat intestine and in increasing the occurrence and severity of degenerative changes. The ability of some sugars to interfere with inhibition of fetal intestinal morphogenesis induced by these peptides was also tested. Mannan at a concentration of 0.1 mM was effective in allowing intestinal morphogenesis to take place in the presence of prolamine peptic-tryptic-cotazym and prolamine peptic-tryptic digests of the four toxic cereals. Some oligomers of N-acetylglucosamine were also effective in blocking the inhibitory effect of “bread” wheat gliadin peptides. These data are compatible with the hypothesis that some sugars may exert a protective effect on the toxic activity of cereal prolamin peptides on the human celiac intestine.

ABSTRACT: Peptic-tryptic-Cotazym (PTC) digests were obtained, simulating in vivo protein digestion, from rice, maize, rye, oats, barley, and sorghum prolamines and tested on small intestine cultures from rat fetus. The PTC digests of the prolamine fractions from rice and maize, even when tested at a concentration as high as 0.5 mg/ml, did not affect in vitro differentiation and maturation of fetal rat jejunum that took place in vitro in a way comparable to what happens in vivo. On the contrary, the PTC digests of prolamines from rye, oats, barley, and sorghum were very active in slowing down in vitro development of fetal rat intestine. These results further strengthen earlier findings and all together show that there is a strong correlation between toxicity results of cereal and/or cereal components assessed with clinical trials or in vitro systems based on bioptic specimens of intestinal mucosa from celiac patients and with the culture of rat fetal intestine. Therefore, the rat fetal intestine culture is considered to be an adequate model for screening and investigating cereal peptides which are toxic for the celiac small intestinal mucosa.

Quantitative data on volatile compounds have been reported in 16 food items. No publications reporting quantitative data were found for two of these 16 food products, i.e. avocado and jackfruit. About 550 volatile compounds have been assayed globally in the other 14 food products. Mango and raspberry were the products with the greatest number of volatile compounds; the most representative substances were benzaldehyde, ethyl acetate, limonene, and 2-phenylethanol.

In this paper we present a compilation of quantitative literature data on volatile compounds in 15 food items including some brandies, meats, oils as well as vegetables, vinegar and potatoes. Levels of the volatile compounds identified (approximately 900) in this group of food items are generally in the ppm range. Carboxylic acids were present in much higher levels in plum brandy, vinegar, lamb and mutton (heated), whereas alcohols, esters and carbonyls aldehydes are particularly abundant in brandy.

The WA84 experiment at CERN has been proposed as a study of heavy-flavour physics using a novel, high-resolution vertex detector, consisting of an active target assembled from coherent bundles of scintillating optical microfibers. This paper is a presentation of work carried out in the development of the vertex detector. Results from tests of prototypes of the detector in a charged-particle beam are reported, and the differences in the performance of glass and plastic active targets are discussed.

Samples (633) of final coffee products were drawn from the markets of different European countries relative to the market share of each product type and brand. These samples were analysed in a cooperative action with nine different laboratories. With low limits of detection (mean detection limit ≈ 0.5 ng/g) no OTA was found in over half of the samples (334 negatives). In the remaining samples occurrence of OTA at a rather low level was seen. Only four samples (all instants) exceeded a level of 10 ng/g, whereas for both instants, and roast and grounds (R & G), over three-quarters of the samples were in the range from non-detectable to 1 ng/g. The overall mean for all R & Gs was 0.8 ng/g and for all instant 1.3 ng/g (for samples in which no OTA was detected, half of the detection limit was included in this calculation). In the brewing methods frequently used in Europe the OTA is essentially fully extracted. Consumption of f our cups of coffee per day (≈ 24 g R & G or ≈ 8 g instant coffee) contributes on average 19 or 10 ng/day respectively. Four cups/day is above the per caput consumption level in most European countries. Compared with the Provisional Tolerable Weekly Intake (PTWI) recently set by the Joint FAO/WHO Expert Committee on Food Additives at 100 ng/kg bodyweight/week, consumption of 28 cups/week contributes up to 2% to the PTWI.

This paper is a compilation of quantitative data available on volatile compounds reported so far in 18 food items including some legumes, cereals, grapes and cheeses as well as crab, lobster, cocoa and chocolate. No publications reporting quantitative data were found for five of these 18 food products, i.e. sultana grape, broad beans, cassava, oat and rye. About 440 volatile compounds have been assayed globally in the other 13 food products and more than 50% of them were found in grape or in grape juice. Levels of these voltatile compounds in the selected foods were generally in the ppb range and less often in the low ppm range. Very high levels were found for some carboxylic acids in cheeses and cocoa and for some alcohols and acids as well as for ethyl acetate in grape juice.

Subfraction 2R of fraction 9 from a peptic-tryptic-pancreatic digest of wheat gliadin is known to be toxic in vivo to celiac patients. We have found that fractions 9 and 2R inhibit the in vitro development of fetal rat intestine and the increase of enterocyte height occurring in organ culture of atrophic celiac mucosa (0.1–0.5 mg/ml medium). Other peptide fractions of the gliadin digest are devoid of such in vitro effects. Subfraction 2R, after incubation with morphologically normal small intestinal mucosa of celiacs in remission and ultrafiltration, was still very active in both culture systems at low concentration (0.1 mg/ml); on the contrary, subfraction 2R was inactivated after incubation with normal mucosa. These results are compatible with the hypothesis that there is a mucosal defect in handling gliadin peptides in celiac disease, and suggest that there is either a primary (or secondary) enzyme deficiency or some other mechanism operating in the intestinal mucosa of celiac patients in remission. (Pediatr Res 24: 233–237,1988)

Summary: Peptic-tryptic-cotazym (PTC) digests were obtained, simulating in vivo protein digestion, from albumin, globulin, gliadin and glutenin preparations from hexapiod (bread) wheat as well as from diploid (monococcum) and tetraploid (durum) wheat gliadins. The digest from bread wheat gliadins reversibly inhibited in vitro development and morphogenesis of small intestine from 17-day-old rat fetuses, whereas all the other digests (obtained both from nongliadin fractions and from gliadins from other wheat species) were inactive.The PTC-digest from bread wheat gliadins was also able to prevent recovery of and to damage the in vitro cultured small intestinal mucosa from patients with active coeliac disease (gluteninduced entheropathy). The PTC-digest from durum wheat gliadins caused a much less adverse effect on this human pathologic tissue culture system.Speculation: When tested with different in vitro systems, bread wheat gliadin peptides active in coeliac disease displayed several peculiar biologic activities including an immunogenic character in susceptible individuals (Z), a probable immunomediated cytotoxic activity on small intestinal mucosa specimens from coeliac patients (6-10, 13-15, 17), and a probable direct cytotoxic activity on developing rat fetal intestine (5). In fact, these peptides induce the following: (I) proliferation of peripheral blood lymphocytes from coeliac patients as well as from many first degree relatives of coeliacs and from only a few normal controls; (2) damage of the in vitro cultured small intestinal mucosa of patients with active coeliac disease; and (3) reversible inhibition of the in vitro development of fetal rat intestine.Although no one of the mentioned in vitro systems can be considered a model fully representative of coeliac disease, it is likely that each one of them highlights a different important feature underlying the appearance of the small intestine lesion in coeliac patients ingesting bread wheat gliadin peptides. Peptide mixtures obtained by enzymic digestion of the gliadin fraction from hexaploid (bread) wheats significantly differ from those from tetraploid (durum) wheat gliadins for their higher toxicity toward cultures of intestine from rat fetuses or coeliac children. However, gliadin peptides from both bread and durum wheats are capable of inducing proliferation of peripheral blood lymphocytes from coeliac patients thus suggesting a similar immunogenic character (2).We suggest that durum wheat gliadins peptides are in vitro less toxic than bread wheat gliadins peptides for the small intestinal mucosa of coeliacs as they have less direct cytotoxic effect on the enterocyte; moreover, durum wheat products (e.g., spaghetti), as compared to bread wheat products (e.g., bread and biscuits), migh present a lower risk for patients suffering for coeliac disease or other wheat intolerances.

Background: Whereas no clear relationship has been observed between varicocelectomy and serum inhibin B levels in men, in adolescents comparison between inhibin B levels before and after varicocelectomy is lacking. Aim: To evaluate the effect of varicocele surgical treatment on inhibin B levels in adolescents at the beginning of puberty compared to a group of healthy adolescents. Subjects and methods: We studied 28 adolescents in Tanner 2 pubertal stage with a grade III left-sided varicocele (patients) compared to 13 age- and pubertal stage-matched healthy adolescents (controls). All patients underwent blood tests to determine serum inhibin B levels before and 6 months after varicocelectomy by Palomo procedure. For comparison we investigated inhibin B levels in controls and repeated this test 6 months later. Testicular ultrasound was performed for patients only. Results: Baseline inhibin B concentrations of patients and controls were 109.90±40.26 and 109.33±38.34 pg/ml, respectively. No significant changes were observed in patients’ inhibin B concentrations after varicocelectomy (116.00±42.65 pg/ml), or in controls during the 6 months’ follow-up (99.12±30.09 pg/ml). Doppler examination after treatment shows a complete resolution of varicocele in all the patients without alterations in testicular parenchyma. Conclusions: Varicocelectomy performed on adolescents at T2 pubertal stage might be useful to avoid alteration in inhibin B production and consequently in testicular function. Further studies are necessary to confirm the prognostic value of inhibin B levels and the benefit of early varicocelectomy in preserving the fertility of these adolescents.

In order to demonstrate that gliadin peptides may interact with cell membranes of celiac small intestinal mucosa, the capacity of these peptides to activate the cell membrane enzyme adenylate cyclase was tested. The addition of peptides from bread wheat purified A-gliadin and whole gliadin (proteins that are toxic for celiac patients) enhanced the adenylate cyclase activity of crude cell membrane preparations obtained from atrophic small intestinal mucosa of celiac patients. No activation of adenylate cyclase of this tissue was observed with peptides from proteins nontoxic for celiac patients (bread wheat albumin and maize prolamin). Gliadin peptides did not activate adenylate cyclase of morphologically normal small intestinal mucosa from normal subjects or from celiac patients in remission. These results, therefore, suggest that peptides from bread wheat gliadin may interact with cell membrane of atrophic small intestinal mucosa of celiac patients.

ABSTRACT. In order to demonstrate that gliadin peptides may interact with cell membranes of celiac small intestinal mucosa, the capacity of these peptides to activate the cell membrane enzyme adenylate cyclase was tested. The addition of peptides from bread wheat purified A-gliadin and whole gliadin (proteins that are toxic for celiac patients) enhanced the adenylate cyclase activity of crude cell membrane preparations obtained from atrophic small intestinal mucosa of celiac patients. No activation of adenylate cyclase of this tissue was observed with peptides from proteins nontoxic for celiac patients (bread wheat albumin and maize prolamin). Gliadin peptides did not activate adenylate cyclase of morphologically normal small intestinal mucosa from normal subjects or from celiac patients in remission. These results, therefore, suggest that peptides from bread wheat gliadin may interact with cell membrane of atrophic small intestinal mucosa of celiac patients.

ARGO-YBJ (Astrophysical Radiation with Ground-based Observatory at YangBaJing) is a detector optimized to study small size air showers. It consists of a layer of Resistive Plate Counters (RPCs) covering an area of ~ 6500 m2and will be located in the Yangbajing Laboratory (Tibet, China) at 4300 m a.s.l. ARGO-YBJ will be devoted to a wide range of fundamental issues in cosmic rays and astroparticle physics, including in particular gamma-ray astronomy and gamma-ray bursts physics in the range $10~{\rm GeV} \div 500~{\rm TeV}$. The sensitivity of ARGO-YBJ to detect high energy GRBs is presented.

Results are presented on the production characteristics of charmed particles obtained from the WA75 emulsion hybrid experiment. The events, selected by the presence of a muon with a high momentum transverse to the beam direction, were located and analysed in nuclear emulsions. Inclusive and correlation properties are systematically compared with the lowest-order QCD calculations for DD hadroproduction. Results concerning the correlation properties indicate some contribution from next-to-leading order [O(αS3)] subprocesses.

Results are presented on the production cross-section of charmed particles obtained from the WA75 emulsion hybrid experiment. The events, selected by the presence of a muon with a high momentum transverse to the beam direction, were located and analysed in nuclear emulsions. A Monte Carlo simulation allowed the computation of acceptances due to both apparatus and selection, as well as scanning and finding efficiencies. The cc hadroproduction cross-section has been determined over the entire xF region as σ(cc) = 23.1 ±1.3(stat)+4.0-3.3(syst) µb per nucleon assuming an A0.87 dependence.