bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophoretic types of leucine aminopeptidase in sheep serum
Authors: Llanes D. , Barbancho M. , Morera L. , Rodero A.
Published: August 2010

Leucine aminopeptidase in sheep serum was studied by starch gel electrophoresis. Two phenotypes, A and B, were observed, of which the former was present in 70–90 % of all the sheep examined. These two phenotypes have been shown to be controlled by a single autosomal locus, with two alleles LayA and LapB. The LapA allele is dominant. The frequencies of Lap phenotypes and alleles were determined in eleven Spanish and two foreign breeds. Serum alkaline phospatase and serum leucine aminopeptidase are electrophoretically distinct.
Sources of bovine lymphocyte antigen (BoLA) typing reagents*
Authors: Amorena B. , Stone W. H.
Published: August 2010

Sera from about 1000 cows were tested for cytotoxicity against a panel of up to 100 lymphocyte samples. Cytotoxic antibodies presumably resulting from trans‐placental immunization of the cow by her calf were found in about 45% of these sera. The antibody titers of sera from parous cows rarely exceed 42, some persisted for over one year, but decreased notably at calving. Thirty‐five immune sera were also produced by alloimmunization with lymphocytes. They usually reached peak titers of up to 44 at 2 or 3 weeks after the initial immunization. Subsequent immunizations produced sera with very high titers but they were much more polyspecific. High‐titered antibodies were also produced by skin graft recipients. Useful cytotoxic antibodies were found in 19 of 111 colostrum whey samples. Studies on 13 dam‐calf pairs showed that the newborn calf may acquire cytotoxic antibodies from its mother's colostrum, but the only cytotoxic antibodies detectable in this calf s serum are those not directed against its own lymphocyte antigens. It is concluded that efficient lymphocyte typing requires antibodies from a variety of sources.
A simple technique using skin implants to produce histocompatability (BoLA) typing sera*
Authors: Pringnitz D. J. , McLaughlin K. , Benforado K. , Strozinski L. , Stone W. H.
Published: August 2010

We describe a technique to produce high‐titered bovine lymphocytotoxic anti‐sera using skin implants. The main advantage of this technique is that the skin does not need to be processed prior to implantation and no surgical skill is required. In addition, the skin can be stored for up to 2 weeks and can be shipped to other laboratories without special handling and without loss of immunogenicity.
Genetic variation in a population of the wild quail Coturnix coturnix japonica
Authors: Kimura Masao , Kato Hideki , Ito Shin‐ichi , Isogai Iwahiro
Published: August 2010

To investigate genetic variation and to compare it with those of domestic quail populations, enzymatic and non‐enzymatic proteins in a wild quail population were examined electrophoretically.

The wild quail population had a genetic variability considerably lower than those of domestic populations. The average heterozygosity estimated for 22 loci was 0.090 in the wild quail population.
Sorbitol dehydrogenase genetics in the mouse: A ‘;null’ mutant in a ‘;European’ C57BL strain
Authors: Holmes Roger S. , Duley John A. , Hilgers J.
Published: August 2010

A ‘;null’ activity variant phenotype for sorbitol dehydrogenase (SDH) was observed in C57BL/LiA mice and used to examine the genetics of this enzyme. Linkage studies of the locus (Sdh‐1) with non‐agouti (a) and a biochemical Iocus encoding liver L‐α‐hydroxyacid oxidase (Hao‐1) demonstrated that it is coincident with or closely linked to the structural locus, previously localized on chromosome 2. Alcohol dehydrogenase (ADH) isozymes were also examined, since the liver A2 isozyme exhibited some activity as a sorbitol dehydrogenase on cellulose acetate zymograms. It is apparent that SDH activity is not ‘;essential’ in this mouse strain.
Linkage between genes at the H blood group locus and the loci for C and J blood groups in pigs*
Authors: Rasmusen B. A.
Published: August 2010

A frequency of recombination between genes at the H and C blood group loci of θ= 115/271 = 0.424 ± 0.030 and between genes at the H and J blood group loci of θ= 831199 = 0.417 ± 0.035 has been calculated in pigs.
The pig histocompatibility system SLA: Serological study on a group of antigenic specificities
Authors: Renard Christine , Chardon P. , Vaiman M.
Published: August 2010

The report presents an analysis of a group of class I SLA reagents which were highly correlated within one cluster in a previous analysis. Further population and family studies, and selected purification of several of these reagents led to the identification of 4 distinct specificities, namely SLA A 15, B 18, C 1 and A 16. Three of them, SLA A 15, B 18 and C 1, are actually in strong linkage disequilibrium and represent the main SLA haplotype in the Large White breed. SLA A 16 is present essentially in the Landrace breeds. SLA A 16 displays a strong cross‐reaction with SLA A 15 and there is another specificity in linkage disequilibrium with SLA A 16 which cross‐reacts with SLA B 18. Altogether, the strong linkage disequilibrium and the high degree of cross‐reactivity among the allelic products of the SLA complex explain the failure to detect the diversity of our reagents in previous studies.
Biochemical polymorphisms in goats with special reference to the Hungarian Native breed
Authors: Fésüs L. , Várkonyi J. , Áts Ágnes
Published: August 2010

Biochemical polymorphisms (haemoglobin, serum transferrin, serum albumin, serum amylase, red cell phosphohexose isomerase, red cell carbonic anhydrase, ceruloplasmin and aryl esterase) of 224 Hungarian Native female goats and 21 imported male goats (German Improved, Saanen, Nubian, Slovakian White) have been studied.

On the basis of the observed gene frequency values these polymorphic traits cannot be used efficiently in parentage control work or in correlation studies. There was no apparent association between the haemoglobin and transferrin type of the females and their reproductive performance.
Glucosephosphate isomerase poiymorphism in sheep
Authors: M. Beatty Elspeth , L. Doxey D. , FitzSimons J.
Published: August 2010

Two types of glucosephosphate isomerase (GPI) are described for the first time in sheep. Type T produced a 3‐b and pattern on polyacrylamide gel electrophoresis of serum samples, whereas type M produced a pattern of 5–7 bands. When 23 Scottish Halfbred ewes showing type T were mated to 3 Suffolk rams showing type M, their 32 offspring had frequencies of 0.72 and 0.28 for T and M respectively. There was no conclusive evidence that the types were controlled by codominant alleles or by simple Mendelian inheritance and neither was sex‐linked. The frequency of the rarer type (M) was sufficiently high to provide conclusive evidence of true enzyme polymorphism.
Equine marker genes: Polymorphism for plasminogen
Authors: R. Weitkamp L. , Costello‐Leary P. , A. Guttormsen S.
Published: August 2010

Polymorphism for two autosomal alleles of equine plasminogen, PLG1 and PLG2, was demonstrated in plasma by isoelectric focusing and immunofixation, with a goat anti‐human plasminogen antibody. The frequency of PLC2 was 0.16 in 150 Standardbreds, 0.20 in 96 Thoroughbreds, and 0.39 in 32 Shetland ponies. No evidence for linkage of PLG with any of 13 marker loci was found.
A bovine ‘Ia‐like’ antigen detected by a xenogeneic monoclonal antibody
Authors: ‐J. Letesson J. , Coppe Ph. , Lostrie‐Trussart N. , Depelchin A.
Published: August 2010

A monoclonal antibody termed B2 Val 7C7, was produced by the fusion of xenoimmune mouse spleen cells with Sp2/0.Ag 14 myeloma cells. This antibody is specific for a polymorphic lymphocyte antigen; it was detected on cells from 138 out of 177 cattle by both 125I‐labelled protein A (solid‐phase radioimmunoassay, SPRIA) and gold‐labelled protein A (immunogold). Its binding was tested on various cell types (peripheral blood lymphocytes, monocytes, polymorphonuclear cells (PMN), thymocytes) from a variety of normal bovine donors. On the one hand, B2 Val 7C7 detects a determinant present on all IgG‐bearing lymphocytes, on 20 % of the non‐IgG‐bearing lymphocytes and on the majority of the monocytes. On the other hand, no binding occurs on any PMN or thymocytes. The detected membrane antigen was isolated by immunoprecipitation from an NP 40 extract of 3H‐leucine‐labelled cells. On SDS‐PAGE, it appears to be composed of two sub‐units: a 32 000‐dalton chain and a 27 000‐dalton chain. These results show that B2 Val 7C7 recognizes an alloantigenic specificity present on an Ia‐like antigen
Genetic polymorphism of the vitamin D binding protein (Gc protein) in pig plasma determined by agarose isoelectrofocusing
Authors: Ljungqvist L. , Hyldgaard‐Jensen J.
Published: August 2010

Genetic polymorphism of the pig plasma vitamin D binding protein Gc was demonstrated by agarose isoelectrofocusing followed by either autoradiography or immunofixation with specific human Gc antiserum. Three different types F, FS and S were observed. Family data supported the genetic theory that the Gc types are controlled by two autosomal codominant alleles GcF and Gcs. Both alleles are present in Yorkshire and Duroc. In Danish Landrace and Hampshire only the GcF allele was observed.
Non‐MHC alloantigenic system in pigs (SLC) detected by leucoagglutination
Authors: Hruban V. , Dvořàk P. , Hradecký J. , Pazdera J. , Müller J.
Published: August 2010

Two cell membrane leucocyte alloantigens were detected in pigs by simple direct agglutination tests. Family studies showed that the locus controlling these antigens was not identical, or in close linkage, with the SLA major histocompatibility complex, SLB leucocyte locus or with the A, E, and N blood group loci. In the studied population, the locus termed SLC (Swine Leucocyte C locus) has two alleles controlling mutually exclusive antigens SLC‐1 and SLC‐2. The frequency of SLC1 and SLC2 alleles is 0.10 and 0.90, respectively. The antigens have not been detected on erythrocytes and thrombocytes but are well determined on granulocytes, peritoneal macrophages, mononuclears from different sources (thymus, spleen, bone marrow, lymph nodes) and enriched T and B cells from peripheral blood.
Polymorphism and inheritance of serum esterases and β‐globulins in the paradise fish (Macropodus opercularis; Anabantidae)
Authors: Monostory Zsuzsa , Nagy András , Gervai Judit , Csányi Vilmos
Published: August 2010

Electrophoretic variants of serum esterases and β‐globulins in two subspecies of paradise fish (Macropodus opercularis) were studied. Four esterase loci (Est‐1, Est‐2, Est‐3 and Est‐4), a single transferin (Tf) and another major β‐globulin locus (Bg) were identified by segregational analysis. Est‐3 seems to be a monomorphic. locus. Three alleles of Est‐1, two of Est‐2, two of Est‐4, four of Tf and two alleles of Bg were found in the laboratory population. None of these loci were closely linked. Electrophoretic patterns of F1 hybrids confirmed the monomeric structures of each of the studied proteins. Allelic segregation at the Tf and Bg loci was normal in F2 and backcross populations. In crosses of the two Macropodus subspecies there were deviations from Mendelian ratios because of missing recombinant esterase phenotypes. Each of these would have been homozygous Est‐2f/f. We suppose that Est‐2f/f causes lethality in the early phase of development, except in the Est‐1c/c, Est‐2f/f combination characteristic of the parental subspecies M.o. concolor.
Genetic polymorphism of the vitamin D binding protein (Gc) in the musk shrew (Suncus murinus)
Authors: Iseki Rieko , Kondo Kyoji
Published: August 2010

In the musk shrew (Suncus murinus), the electrophoretic bands in the post‐albumin region were identified as vitamin D binding protein (Gc) by the [3HI vitamin D3 binding method. Three Gc phenotypes were distinguished from each other: a single faster band (Gc‐A), a single slower band (Gc‐B) and the double bands (Gc‐AB). Results of mating experiments indicated that the Gc‐A and Gc‐B are controlled by two codominant alleles, Cca and Gcb at an autosomal locus (Cc), respectively. It was noticed that, in the Gc‐AB phenotypes, the Gc‐B band was constantly more intense than the Gc‐A band in the protein staining. The same tendency was also observed btween the homozygous Gc‐A and Gc‐B bands, and further, radioactivity of the Gc‐B bound with [3H] vitamin D3 was about twofold higher than that of the Gc‐A. These results suggest that the Gcb yields its protein product twofold more than the Gca. No cross‐reaction between the shrew proteins and a rabbit anti‐human Gc protein was observed.
Protein polymorphism in the fresh water snail Sernisulcospira libertina
Authors: Kimura Masao , Oniwa Kiyoko
Published: August 2010

To evaluate genetic variability in 19 population samples of the fresh water snail Semisulcospira libertina, 10 enzymes coded for by 13 presumptive gene loci were examined by starch gel electrophoresis. The mean proportion of polymorphic loci and the mean heterozygosity value estimated for the 19 samples were 0.199 and 0.063, respectively. The mean F statistics of Wright (1943) was estimated over the four polymorphic loci (PGM, 6‐PGD, MPI and PGI) for the snail populations to be 0.3615.
Abnormal segregation of alkaline ribonuclease genes in cattle1
Authors: Walawski K. , Glogowska B. , Kaźmir Z.
Published: August 2010

Polymorphism of alkaline ribonuclease in the leucocytes of 76 bulls, 554 cows and their progeny of 556 calves was investigated. All possible genotype matings were examined. Observed offspring genotypes were compared with the expected ratios. Abnormal genotype distribution was noticed: homozygous calves of RNaseB/RNaseB genotype were significantly fewer than expected.
Heterogeneity of horse transferrin: the role of carbohydrate moiety
Authors: Stratil A. , Tomášek V. , Bobák P. , Glasnák V.
Published: August 2010

Homozygous horse transferrin (Tf O) is highly heterogeneous. In starch gel electro‐phoresis it gives at least 9 zones. Two main components (2a and 4b) were purified by rivanol and ammonium sulphate precipitation, DEAE‐Sephadex chromatogra‐phy and SP‐Sephadex chromatography. Molecular weights of 75 200 and 80 500 for components 2a and 4b, respectively, were determined by sedimentation equilibrium ultracentrifugation. Amino acid compositions of the two components were similar, and there were no differences in the N‐terminus (glutamic acid followed by glu‐tamine) and the C‐terminus (valine). Differences were found in carbohydrate composition between components 2a and 4b. Component 2a contained 10 moles of sugar components per mole of protein (4 hexoses, 4 hexosamines and 2 sialic acids), while component 4b contained twice the number of both total carbohydrates and individual sugar components. Carbohydrates were identified as mannose and galac‐tose (ratio mannose:galactose = 1.5:l), N‐acetylglucosamine and N‐acetylneu‐raminic acid. At present it is not clear whether the difference between the two components resides solely in the difference of carbohydrate contents. It is proposed that component 2a has one diantennary glycan, while component 4b has two.
The plasma protease inhibitor system (Pi) of Standardbred horses
Authors: Bell K. , Patterson S. , Pollitt C. C.
Published: August 2010

The plasma protease inhibitor system (Pi) of Standardbred horses was studied by thin‐layer, high‐voltage, acid polyacrylamide gel electrophoresis (pH 4.6) followed by protein staining and staining for trypsin and chymotrypsin inhibition. In addition to the eight Thoroughbred alleles (PiF, g, i, L, N, S1, S2, u), another 10 alleles, designated PiH, j, k, o, p, q, r, v, x, z, were postulated to account for the 98 Pi types which were observed in Standardbreds. Detailed inhibitory spectra of the ‘new’ alleles were determined and further exceptions to the Pil, Pi2 classification of Juneja et al. (1979) were found. Limited family data demonstrated the genetic nature of the ‘new’ variants and confirmed the allelic inheritance of the ‘new’ Pi variants.
Comparison of bovine serum transferrin A and D2. II. Glycopeptides
Authors: Maeda K. , A. McKenzie H. , C. Shaw D.
Published: August 2010

Glycopeptides are isolated from subtilisin and pronase digests of whole bovine serum transferrin A and D2. The two variants yield glycopeptides with identical ami‐no acid composition. Hence, there is probably no amino acid substitution in this region of the peptide chain. Amino acid sequence determination of one glycopeptide (subtilisin glycopeptide 8) gives the sequence: (CHO)Asn‐Ser‐Ser‐Leu‐Cys. This sequence is identical with that of residues 491–495 of the sequence for human serum transferrin (MacGillivray et al., 1982) except that in the bovine transferrin, Asp is replaced by Asn, enabling carbohydrate attachment. A second glycopeptide sequence Arg‐(CHO)Asn‐Ala‐Thr‐Tyr is observed, and the significance discussed in relation to carbohydrate moieties of serum glycoproteins.
The occurrence of the feline A blood group antigen on lymphocytes
Authors: Symons R. , Bell K.
Published: August 2010

Sera from 300 cats were tested for the presence of anti‐lymphocytic antibodies. One hundred and nineteen sera showed some activity with the majority (79) reacting only with lymphocytes from blood group A cats. Absorption of two such sera with A, AB and B erythrocytes and absorption of AB system reagents with lymphocytes from A and B blood group cats demonstrated that the A antigen is expressed on both erythrocytes and lymphocytes. Blood group and lymphocyte typing tests of foetuses indicated that the A antigen is present on these tissues as early as 46 days gestation. The erythrocytic B antigen could not be demonstrated on lymphocytes although a single antiserum, which reacted against lymphocytes from group B cats, was found. Several sera containing anti‐lymphocytic antibodies which were not related to the AB type were also detected.
Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers
Authors: Wootton R. , Soul‐Lawton J. , Rolan P. E. , Sheung C. T. C. Fook , Cooper J. D. H. , Posner J.
Published: August 2010

Aims The aim of this study was to compare the pharmacokinetics of the anti‐epileptic agent, lamotrigine, in patients with chronic renal failure and healthy volunteers.

Methods Non‐compartmental pharmacoknetics of a single oral dose (200 mg) of the anti‐epileptic agent, lamotrigine, and its main metabolite, lamotrigine N2‐glucuronide, were determined for 10 patients with chronic renal failure of mean estimated creatinine clearance 18ml min−1 and a control group of 11 healthy volunteers, matched for age and gender.

Results For lamotrigine, there were no significant differences in Cmax, tmax, AUC, t 1/2, z, CL/F and amount excreted in urine although t 1/2, z, tended to be longer for the renal failure group with a mean (± s.d.) of 35.9 ± 10.7 h vs 27.8 ± 4.3 h for the control group. For the renal failure group, Vz/F was 18% higher (95% Cl 1% to 39%) compared with controls and CLR was reduced to 61% (95% Cl 46% to 80%) of the control group value. For lamotrigine glucuronide, Cmax, was increased 4‐fold (95% Cl 3.1 to 5.3) and AUC 7.8–fold (95% Cl 6.0 to 10.1) in the renal failure group compared with controls. CLR was approximately 9‐fold lower and apparent t1/2 was increased by 53% (95% Cl 27% to 84%). Concentrations of an N2 ‐methylated cardo‐active metabolite, previously observed in dogs, were below the limit of detection (2 ng ml−7) of the ASTED/h.p.l.c. assay in the renal failure group as well as controls.

Conclusions These results indicate that impaired renal function will have little effect on the plasma concentrations of lamotrigine achieved for a given dosing regimen.
Initial human experience with MK‐462 (rizatriptan): a novel 5=HTID agonist
Authors: Sciberras David G. , Polvino William J. , Gertz Barry J. , Cheng Haiyung , Stepanavage Michael , Wittreich Johanna , Olah Timothy , Edwards Mark , Mant Timothy
Published: August 2010

Aim We evaluated the pharmacokinetics and pharmacodynamics of oral MK‐462 in comparison with oral sumatriptan in healthy male volunteers.

Methods Sixteen healthy male volunteers were studied in a rising, single dose, alternating panel design with eight subjects per panel. Matching placebo was administered to two of eight study subjects at each dose level of MK‐462 in a randomized, double‐blind fashion.

Results MK‐462 was rapidly absorbed with a median tmax of 1.3 h (range 1–3 h) vs a tmax for sumatriptan of 2.5 h (range 1–4 h, P < 0.001). Administration of either MK‐462 or sumatriptan produced maximal mean elevations of 5–10 mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following MK‐462, consistent with more rapid absorption. Both MK‐462 and sumatriptan provoked mild increases in serum growth hormone without any effect on serum prolactin concentrations. The most commonly reported symptom following MK‐462 was drowsiness.

Conclusions These results indicate that the novel 5‐HT1D agonist, MK‐462, is rapidly absorbed following oral administration and warrants further investigation of its utility in the treatment of acute migraine.
Therapeutic drug monitoring of psychotropic medications
Authors: Mitchell Philip B.
Published: August 2010

Therapeutic drug monitoring (TDM) of a number of psychotropic medications has proven to be of value, enabling minimization of the limitations of considerable genetic variability in their metabolism and the high rates of poor compliance with many psychiatric disorders. Therapeutic ranges have been established for lithium, some of the tricyclic antidepressants, and clozapine. TDM has also been shown to be useful in avoiding toxicity (as many psychotropics have narrow therapeutic indices), particularly that due to interactions with other compounds.
The therapeutic monitoring of antimicrobial agents
Authors: Begg Evan J. , Barclay Murray L. , Kirkpatrick Carl M. J.
Published: August 2010

Aims  To review the basis and optimal use of therapeutic drug monitoring of antimicrobial agents.

Methods  Antimicrobial agents for which a reasonable case exists for therapeutic drug monitoring are reviewed under the following headings: pharmacokinetics, why monitor, therapeutic range, individualization of therapy, sampling times, methods of analysis, interpretative problems and cost‐effectiveness of monitoring.

Results  There is a strong historical case for monitoring aminoglycosides. The recent move to once‐daily dosing means that criteria for therapeutic drug monitoring need to be redefined. Vancomycin has been monitored routinely but many questions remain about the most appropriate approach to this. A case can be made for monitoring teicoplanin, flucytosine and itraconazole in certain circumstances.

Conclusions  The approach to monitoring aminoglycosides is being redefined in the light of once daily dosing. It may be that less stringent monitoring is required in some circumstances but toxicity, especially ototoxicity, remains a problem with these drugs. Monitoring to avoid high AUCs (areas under the concentration‐time curve) is recommended. The ideal method for monitoring vancomycin remains to be defined although a reasonable case exists for measuring trough concentrations, mainly to ensure efficacy. Teicoplanin is sometimes monitored to ensure efficacy while flucytosine may be monitored to avoid high concentrations associated with toxicity. Itraconazole has various pharmacokinetic problems and monitoring has been suggested to ensure that adequate concentrations are achieved.
Simultaneous fitting of R‐ and S‐ibuprofen plasma concentrations after oral administration of the racemate
Authors: Lötsch Jörn , Muth‐Selbach Uta , Tegeder Irmgard , Brune Kay , Geisslinger Gerd
Published: August 2010

Aims To assess the pharmacokinetic equivalence of two different formulations of ibuprofen lysinate with special focus on the expected effects.

Methods Sixteen healthy volunteers received cross‐over ibuprofen lysinate as either one tablet of 400 mg (‘test’) or two tablets of 200 mg (‘reference’). Ibuprofen plasma concentrations were followed up for 10 h. Bioequivalence was assessed by standard noncompartmental methods. Ibuprofen plasma concentrations were fitted with a model that took bioinversion of R‐ to S‐ibuprofen into account.

Results Peak plasma concentrations of R‐ and S‐ibuprofen were 18.1 and 20 µg ml−1(test), and 18.2 and 20 µg ml−1(reference). Areas under the plasma concentrationvstime curves were 39.7 and 67.5 µg ml−1 h (test), and 41.1 and 68.2 µg ml−1 h (reference). Clearance of R‐ibuprofen was 5.2 (test) and 5 l h−1(reference). A specific plasma concentration was reached with the test formulation about 5 min later than with the reference. Parameters from compartmental modelling were (given for R‐and then for S‐ibuprofen): body clearance: 4.9 and 4.64 l h−1, central volume of distribution: 2.8 and 4.1 l, intercompartment clearance: 5.1 and 5.45 l h−1, peripheral volume of distribution: 4.1 and 5.2 l. The absorption rate constant was 1.52 h−1, and the test but not the reference formulation had a lag time of 0.1 h. Simulations showed similarity between formulations of the expected effects except for a calculated delay of 6 min with the test formulation.

Conclusions Ibuprofen formulations were bioequivalent. The pharmacokinetic model may serve as a basis for future pharmacokinetic/pharmacodynamic calculations after administration of racemic ibuprofen.
Polymorphisms in genes encoding acetylsalicylic acid metabolizing enzymes are unrelated to upper gastrointestinal health in cardiovascular patients on acetylsalicylic acid
Authors: Van Oijen Martijn G. H. , Huybers Sylvie , Peters Wilbert H. M. , Drenth Joost P. H. , Laheij Robert J. F. , Verheugt Freek W. A. , Jansen Jan B. M. J.
Published: August 2010

Background

As acetylsalicylic acid is metabolized by UDP‐glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9), interindividual differences in activity of these enzymes may modulate the effects and side‐effects of acetylsalicylic acid. The objective of this study was to assess whether polymorphisms in UGT1A6 and CYP2C9 genes are related to the prevalence of upper gastrointestinal symptoms in cardiovascular patients using acetylsalicylic acid for secondary prevention of ischaemic heart disease.

Methods

Blood samples were taken from acetylsalicylic acid using patients admitted to the Coronary Care Unit. Dyspepsia‐related health was evaluated at week 2, using a validated upper gastrointestinal complaint questionnaire. A subset of 160 patients responded to a survey and were eligible to participate in this study. DNA was isolated and UGT1A6 and CYP2C9 genotypes were determined using polymerase chain reaction restricted fragment length polymorphism techniques.

Results

Seventy per cent of the patients returned the questionnaire. UGT1A6 and CYP2C9 variant polymorphisms were found in 103 (63%) and 56 (35%) patients, respectively. There was no association between gastrointestinal symptoms and UGT1A6 (OR = 0.80, 95% CI = 0.41–1.56) or CYP2C9 polymorphisms (OR = 0.85, 95% CI = 0.44–1.67).

Conclusions

There was no association between polymorphisms in genes encoding for acetylsalicylic acid metabolizing enzymes on the prevalence of gastric complaints in cardiovascular patients on acetylsalicylic acid.
Obstacles and solutions for spontaneous reporting of adverse drug reactions in the hospital
Authors: Vallano A. , Cereza G. , Pedròs C. , Agustí A. , Danés I. , Aguilera C. , Arnau J. M.
Published: August 2010

Aim

To describe the opinions of hospital physicians concerning problems regarding the spontaneous reporting of adverse drug reactions (ADRs) and ways to solve them.

Methods

A qualitative study was carried out. Fifteen focus groups were conducted among physicians working in a tertiary teaching hospital. A total of 208 physicians from different medical specialities participated. The focus group discussions were recorded by three different observers and the transcripts of each session were analysed for issues and themes emerging from the text.

Results

Four types of obstacles to spontaneous reporting were considered particularly important: (i) problems with the ADRS diagnosis; (ii) problems with the usual workload and lack of time; (iii) problems related to the organization and activities of the pharmacovigilance system; (iv) and problems related to potential conflicts. The potential solutions suggested for improving spontaneous reporting were to define the kind of ADRS which should be reported, to facilitate an easy contact and quick access to the hospital pharmacovigilance system, to facilitate information and support for reporting and feedback of pharmacovigilance activities.

Conclusions

The perception of the different obstacles by the hospital physicians is an important factor in determining the causes of the underreporting of ADRs and addressing these obstacles could lead to an improvement in spontaneous reporting. A closer relationship between the doctors and the pharmacovigilance centre is suggested as a means of solving these problems. More information is needed to improve the spontaneous reporting of ADRS in specialized healthcare.
Incorporating family into the formula: family‐directed structural therapy for children with serious emotional disturbance
Authors: Radohl Tamara
Published: August 2010

Increasingly, policy‐makers and consumers alike have been pushing for inclusion of families in the treatment of children with diagnoses of serious and emotionally disturbed (SED). Further, recent trends in service provision highlight the necessity for creation and utilization of evidence‐based practices (EBP), as well as the need for consumer‐ or family‐driven treatment. Although family therapy is a popular intervention for this population, existing evidence‐based family therapy modalities fail to incorporate family direction in the treatment of children with SED. Moreover, the models studied have involved juvenile offenders, and, to date, little research has been conducted to substantiate their use with the SED population. Family‐directed structural therapy (FDST) is an emerging model that unifies evidence‐based practice with family‐directed care. This model actively involves parents and family members in the change process blending consumer‐based principles with a growing empirical base. In FDST, the family is both the fulcrum of power and source of change in the family. A description of this approach and an exemplar are provided to illustrate application of this model with families of children with SED.
Interleukin‐17: a new role in steroid hypo‐responsiveness?
Authors: Lavender P.
Published: August 2010

Cite this as: P. Lavender, Clinical & Experimental Allergy, 2010 (40) 1293–1294.
Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment
Authors: SOBOSLAY P T , DREWECK C M , HOFFMANN W H , LÜDER C G K , HEUSCHKEL C , GÖRGEN H , BANLA M , SCHULZ-KEY H
Published: August 2010

A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P <0·01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-Iβ, tumour necrosis factor-alpha (TNF-α) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-Iβ, IL-2 and TNF-α in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-γ) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1β and TNF-α increased significantly I and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-γ did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P <0·01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P <0·01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/ CD8+ cell ratio (P=0·001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cells and CD3+TCRγδ+ cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.
Elevated complement activities of sera from patients with high density lipoprotein deficiency (Tangier disease): the presence of normal level of clusterin and the possible implication in the atherosclerosis
Authors: CHOI-MIURA N-H , SAKAMOTO T , OHTAKI S , NAKAMURA H , ISHIZAWA S , TAKAGI Y , GOMI K , TOMITA M
Published: August 2010

Clusterin (apolipoprotein J, SP-40,40), as well as apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II), are apolipoprotein components of high density lipoprotein (HDL), but not of low density lipoprotein. In spite of the deficiencies of apo A-I, apo A-II and HDL in the sera of patients with Tangier disease, clusterin was found in them at normal level. While clusterin was present as the component of HDL with apo A-I in sera of normal donors, it was present as a protein which did not form a complex in sera of Tangier patients. SC5b-9 made from the sera of Tangier patients contained normal amounts of clusterin and was deficient in apo A-I, indicating that clusterin could be incorporated into the SC5b-9 complex without apo A-I. The complement activities of the sera of the patients were higher than those of normal donors. These results may be explained by the deficiencies of apo A-I, apo A-II and HDL in the patients, because they were suggested to be the inhibitors of the reactive haemolysis of complement. The elevated complement activities of the patients might be related to the severe atherosclerotic lesions in Tangier disease.
Inhibition of histone/anti-histone reactivity by histone-binding serum components; differential effect on anti-Hlversusanti-H2B antibodies
Authors: BUSTOS A , BOIMORTO R , SUBIZA J L , PEREIRA L F , MARCO M , FIGUEREDO M A , DE LA CONCHA E G
Published: August 2010

IgG fractions were purified on a protein G-agarose column from sera of both systemic lupus erythematosus (SLE) patients and healthy donors. All IgG fractions, after elution with 0·5 M acetic acid, reacted with histones in an anti-histone ELISA assay, and IgG anti-histone activity was in all instances higher in the IgG fraction than in the corresponding whole serum. This was shown to be due to the presence in serum of histone-binding components that inhibited IgG binding to histones. Both normal human and SLE patients' sera had these histone-binding components, and disparity between serum-positive and -negative anti-histone antibody (AHA) tests was not dependent on differences in the blocking capacity but on IgG antibody levels and avidity. Interaction of normal serum IgG fraction with all five histones was of low avidity, whereas interaction of IgG from AHA-positive SLE sera with both H1 and H2B had high avidity. Low-affinity antibodies to every histone fraction, but also high-affinity anti-H1 antibodies, were preferentially inhibited. Our data indicate that several serum protein components are inhibiting histone/anti-histone interaction and may play a protective role against both high-affinity anti-H1 antibodies present in SLE patients, and natural, low-affinity, anti-histone antibodies. As some acute phase proteins, notably C-reactive protein, bind to histones, it is conceivable that they play such a role. High-affinity anti-H2B antibodies, present in some SLE patients, and not inhibited by these serum components, may, on the other hand, participate in the pathogenesis of the disease.
Human serum mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1): determination of levels in body fluids and identification of two forms in serum
Authors: TERAI I , KOBAYASHI K , MATSUSHITA M , FUJITA T
Published: August 2010

We developed an ELISA for human serum MASP-1, a Cls-like serine protease which is known to function in C4 and C2 activation. We then determined MASP-1 levels in 1063 sera from normal Japanese subjects ranging in age from 3 to 100 years, as well as in certain body fluids using this assay. Individual serum MASP-1 levels ranged from 1·48 to 121·83 μg/ml, with a normal frequency distribution pattern. The arithmetic mean ± s.d. of MASP-1 levels in serum was 6·27 ± 1·85 μg/ml, whereas levels of MASP-1 in cerebrospinal fluid and in urine were almost undetectable. When the mean ± s.d. of serum MASP-1 was calculated for each age group (10 year range) and values were then compared, the age group consisting of 3–9-year-olds (7·54 ± 1·39; μ/ml) was found to have the highest value. When MASP-1 was measured in cord blood, it was shown that levels were already as high as those of 3–9-year-olds. The serum MASP-1 level was found to be as strongly dependent on age as is the serum MBL level. MASP-1 and MBL are thought to play an active part in immunity in younger people. It was found that the serum level of MASP-1 was much higher than that of MBL, and the major portion of human serum MASP-1 appeared to exist in the circulation as a form unbound to MBL.
Tryptophan metabolism and indoleamine 2,3-dioxygenase expression in coeliac disease
Authors: Torres M I , López-Casado M A , Lorite P , Ríos A
Published: August 2010

We have investigated the possible role of the metabolism of tryptophan and activity of the enzyme indoleamine 2,3-dioxygenase (IDO) in the immune regulation of coeliac disease (CD). Serum concentrations of tryptophan and its metabolites kinurenines were determined by high performance liquid chromatography in 24 patients with CD, seven patients with Crohn's disease and five healthy patients. We detected an increase of kynurenine (4·2 µmol/l ± 0·27 versus 2·6 µmol/l ± 0·54, P < 0002) and of the kynurenine/tryptophan ratio in supernatants of coeliac patients (11·5 µmol/l ± 1·01 versus 6·5 µmol/l ± 1·57, P < 0005) in comparison with healthy patients, respectively, and we found no differences with Crohn's disease patients. Immunohistochemistry analysis of intestinal biopsies from CD patients showed an increased expression of IDO, interferon-γ, interleukin-10 and transforming growth factor-β. Our data suggest that a mechanism(s) dependent on tryptophan catabolism might regulate the immune responses in CD.
Changes in circulating lymphocyte subpopulations following administration of the leucocyte function-associated antigen-3 (LFA-3)/IgG1 fusion protein alefacept
Authors: Larsen R , Ryder L P , Svejgaard A , Gniadecki R
Published: August 2010

Alefacept, a recombinant leucocyte function-associated antigen-3 (LFA-3)/IgG1 fusion protein approved for the treatment of psoriasis, is reported to reduce selectively the numbers of circulating CD4+ CD45RO+ and CD8+ CD45RO+ T cells, while sparing the naive cells. The purpose of the present study was to elucidate further the effect of alefacept on various circulating lymphocyte subsets. Sixteen patients, 12 with chronic plaque psoriasis and four with pustular psoriasis, received alefacept 7·5 mg once weekly for 12 weeks. Blood samples collected at study entry and after 12 weeks of treatment were analysed by four-colour flow cytometry. There were statistically significant reductions in the total number of conventional memory (CD45RA– CD27+) and effector (CD45RA– CD27– or CD45RA+ CD27–) T cells, including CD4+ and CD8+ T cells expressing CD161 and CD8+ T cells expressing cutaneous lymphocyte-associated antigen (CLA). Natural killer (NK) T cells were also reduced significantly, while no statistically significant changes were seen in NK cells and CD4+ CD25high cells. The affected subpopulations were all characterized by a high expression of CD2. However, CD4+ CD25low, and CD4+ CLA+ cells, which also expressed relative high levels of CD2, were not reduced significantly. Our results suggest a heterogeneous effect of alefacept on the circulating memory T cell population, indicating that high expression of CD2 may not, by itself, be sufficient to explain the reduction in cell count for a specific subpopulation.
Diffusion of NH+4 and NO−3 mineralized from organic N in soil
Authors: DARRAH P. R. , NYE P. H. , WHITE R. E.
Published: August 2010

The mineralization of native soil organic matter and the simultaneous diffusion of zero NH+4 and NO−3 to a solution sink of zero N concentration was analysed experimentally and theoretically for a fine sandy loam soil. Experimentally, the NH4 and NO3 ions produced in an incubated unsaturated soil column were allowed to diffuse through a sintered glass plate into a stirred solution sink. The distribution of NH+4 and NO−3 in the soil column was measured after various incubation times. The rate of ammonification was measured directly during incubation and the rate of nitrification modelled from nitrifier growth kinetics. A Freundlich equation was used to describe the equilibrium between soluble and exchangeable NH+4 in the soil. Terms for the microbial transformation of N and the adsorption‐desorption of NH+4 were combined with diffusion equations which were solved numerically using finite difference methods. The model constructed was used to predict the NH+4 and NO−3 con‐centration distributions in the soil column, and good agreement was obtained between the experimental and predicted concentration profiles. The use of the model for predicting the diffusive flux of mineral N to the outer surfaces of soil peds, where it is vulnerable to leaching, was demonstrated.
Coupled diffusion and oxidation of ferrous iron in soils. I. Kinetics of oxygenation of ferrous iron in soil suspension
Authors: AHMAD A. R. , NYE P. H.
Published: August 2010

The kinetics of oxidation of iron in an aqueous suspension of a thoroughly reduced low‐humus tropical rice paddy soil were followed by measuring the extractable ferrous iron in the whole suspension and in the solution. Three‐quarters of the initial ferrous iron was oxidized rapidly (first‐order rate constant = 9.2 × 10−5 s−1). The subsequent reaction was slow (first‐order rate constant = 9.4 × 10−7 S−1) and was not studied in detail. The pH fell from 6.6 to 4.9 over the course of the fast reaction. In further experiments the rate of oxidation was followed at constant pH values in the range 6.5 to 4.5. It was concluded that the oxidation of adsorbed iron was much faster than solution iron, and that the adsorbed iron was oxidized at a rate that was nearly independent of the pH. During the reaction some ferrous iron is adsorbed on the ferric hydroxide formed. The proportion of the remaining ferrous iron adsorbed on ferric hydroxide rather than the original exchange surfaces was high at pH > 6.0 and low at pH < 5.0. The rate of oxidation of the ferrous iron was similar whether it was adsorbed on exchange sites or on the ferric hydroxide formed. Since the rate of oxidation of the iron adsorbed on ferric hydroxide was very much slower than that on ferric hydroxide formed in the absence of soil, it is suggested that the rate in soil may be controlled by diffusion of oxygen to the adsorption sites.
Improved prediction of water‐retention properties of clayey soils by pedological stratification
Authors: BRUAND A.
Published: August 2010

The water‐retention properties of clayey soils have been studied at −0.3 × 105 and −15 × 105 Pa matric potentials using three sets of clayey horizons differing in their pedological origin. Measurements were made on small clods collected in winter when swelling is at a maximum. The results are discussed in relation to variations in the clay content and clay fabric. The bulk volume, which appears to be closely related to both clay content and clay fabric, allows the variations in water retained to be explained better than with clay content alone. With clayey horizons originating from a single soil family, differences in water retained can be explained by variations in clay content alone because clay fabric does not change greatly. These results demonstrate the significance of pedological stratification in estimating the water‐retention properties when a single soil characteristic, such as clay content, is used.
Seasonal and inter‐annual variations in the abundance and biomass of Neocalanus plumchrus in continental slope waters off Oregon
Authors: LIU HUI , PETERSON WILLIAM T.
Published: August 2010

Seasonal and inter‐annual variability in the abundance and biomass of copepodid stages of the sub‐arctic oceanic copepod, Neocalanus plumchrus, was studied during the January–May growth season, using an 11‐yr time series of zooplankton samples collected over the upper 100 m of the water column. Abundance and biomass peaks occur in March/April. Abundance and biomass of N. plumchrus were significantly negatively correlated with sea surface temperature and significantly positively correlated with sea surface chlorophyll a, salinity, and density above the pycnocline. The seasonal integrated abundance and biomass of N. plumchrus declined during the warm years (2003–05), and increased during the cold years (2006–08). The date when 50% of the population had passed through stage C5 was significantly negatively correlated with temperature – earlier in warm years and later in cold years. In 3 yr (2003, 2007 and 2008), a second cohort appeared in mid‐May, as indicated by the presence of stages C1 and C2 in the samples. Unusually high abundances of N. plumchrus in the spring of 2007 and 2008 were associated with cool ocean temperatures and an early spring transition in the NCC ecosystem, suggesting that the NCC ecosystem has returned to a cold phase. We discuss the merits of a hypothesis that the N. plumchrus population observed off Oregon is a local population as opposed to one that is expatriated from the Gulf of Alaska.