bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevention of fumonisin B1‐induced neural tube defects by folic acid
Authors: Sadler T.W. , Merrill Alfred H. , Stevens Victoria L. , Sullards M. Cameron , Wang Elaine , Wang Ping
Published: October 2002

Background

The mycotoxin fumonisin B1 (FB1) inhibits sphingolipid synthesis, blocks folate transport, and has been associated with increased incidences of cancer and neural tube defects. Results from reproductive studies in animal models in vivo and in vitro have demonstrated toxicity in some cases, but no specific terata after fumonisin exposure. No information is available about folic acid's potential to protect against this toxicity.

Methods

Neurulating mouse embryos were exposed to fumonisin or folinic acid in whole embryo culture and assessed for effects on growth and development.

Results

Fumonisin exposure inhibited sphingolipid synthesis, reduced growth, and caused cranial neural tube defects in a dose dependent manner. Supplemental folinic acid ameliorated the effects on growth and development, but not inhibition of sphingolipid synthesis.

Conclusion

Fumonisin has the potential to inhibit embryonic sphingolipid synthesis and to produce embryotoxicity and neural tube defects. Folic acid can reverse some of these effects, supporting results showing that fumonisin disrupts folate receptor function. Teratology 66:169–176, 2002. © 2002 Wiley‐Liss, Inc.
Genome‐wide search of Schizosaccharomyces pombe genes causing overexpression‐mediated cell cycle defects
Authors: Tallada Victor A. , Daga Rafael R. , Palomeque Cristina , Garzón Andrés , Jimenez Juan
Published: October 2002

Genetic studies in yeasts enable an in vivo analysis of gene functions required for the cell division cycle (cdc genes) in eukaryotes. In order to characterize new functions involved in cell cycle regulation, we searched for genes causing cell division defects by overexpression in the fission yeast Schizosaccharomyces pombe. By using this dominant genetic strategy, 26 independent clones were isolated from a Sz. pombe cDNA library. The cloned cDNAs were partially sequenced and identified by computer analysis. The 26 clones isolated corresponded to 21 different genes. Among them, six were genes previously characterized in Sz. pombe, 11 were homologues to genes identified and characterized in other organisms, and four represented genes with unknown functions. In addition to known cell cycle regulators encoding inhibitory protein kinases (wee1, pka1) and DNA checkpoint proteins (Pcna, rad24), we have identified genes that are involved in a number of cellular processes. This includes protein synthesis (ribosomal proteins L7, L10, L29, L41, S6, S11, S17 and the PolyA‐Binding Protein PABP), protein degradation (UBI3), nucleolar rRNA expression (fib, imp1, dbp2), cell cytoskeleton (act1) and glycolysis (pfk1). The interference caused in the cell cycle by overexpression of these genes may elucidate novel mechanisms coupling different cellular processes with the control of the cell division. The effect caused by some of them is described in more detail. Copyright © 2002 John Wiley & Sons, Ltd.
Putative xylose and arabinose reductases in Saccharomyces cerevisiae
Authors: Träff K. L. , Jönsson L. J. , Hahn‐Hägerdal B.
Published: October 2002

Saccharomyces cerevisiae mutants, in which open reading frames (ORFs) displaying similarity to the aldo‐keto reductase GRE3 gene have been deleted, were investigated regarding their ability to utilize xylose and arabinose. Reduced xylitol formation from D‐xylose in gre3 mutants of S. cerevisiae suggests that Gre3p is the major D‐xylose‐reducing enzyme in S. cerevisiae. Cell extracts from the gre3 deletion mutant showed no detectable xylose reductase activity. Decreased arabitol formation from L‐arabinose indicates that Gre3p, Ypr1p and the protein encoded by YJR096w are the major arabinose reducers in S. cerevisiae. The ypr1 deletion mutant showed the lowest specific L‐arabinose reductase activity in cell extracts, 3.5 mU/mg protein compared with 7.4 mU/mg protein for the parental strain with no deletions, and the lowest rate of arabitol formation in vivo. In another set of S. cerevisiae strains, the same ORFs were overexpressed. Increased xylose and arabinose reductase activity was observed in cell extracts for S. cerevisiae overexpressing the GRE3, YPR1 and YJR096w genes. These results, in combination with those obtained with the deletion mutants, suggest that Gre3p, Ypr1p and the protein encoded by YJR096w are capable of xylose and arabinose reduction in S. cerevisiae. Both the D‐xylose reductase and the L‐arabinose reductase activities exclusively used NADPH as co‐factor. Copyright © 2002 John Wiley & Sons, Ltd.
Novel human ZAKI-4 isoforms: hormonal and tissue-specific regulation and function as calcineurin inhibitors
Authors: CAO Xia , KAMBE Fukushi , MIYAZAKI Takashi , SARKAR Devanand , OHMORI Sachiko , SEO Hisao
Published: October 2002

We identified a thyroid hormone [3,5,3′-tri-iodothyronine (T3)]-responsive gene, ZAKI-4, in cultured human skin fibroblasts. It belongs to a family of genes that encode proteins containing a conserved motif. The motif binds to calcineurin and inhibits its phosphatase activity. In the present study, we have demonstrated three different ZAKI-4 transcripts, α, β1 and β2, in human brain by 5′- and 3′-RACE (rapid amplification of cDNA ends). The α transcript was identical with the one that we originally cloned from human fibroblasts and the other two are novel. The three transcripts are generated by alternative initiation and splicing from a single gene on the short arm of chromosome 6. It is predicted that β1 and β2 encode an identical protein product, β, which differs from α in its N-terminus. Since α and β contain an identical C-terminal region harbouring the conserved motif, both isoforms are suggested to inhibit calcineurin activity. Indeed, each isoform associates with calcineurin A and inhibits its activity in a similar manner, suggesting that the difference in N-terminus of each isoform does not affect the inhibitory function on calcineurin. An examination of the expression profile of the three transcripts in 12 human tissues revealed that the α transcript is expressed exclusively in the brain, whereas β transcripts are expressed ubiquitously, most abundantly in brain, heart, skeletal muscle and kidney. It was also demonstrated that human skin fibroblasts express both α and β transcripts, raising the question of which transcript is up-regulated by T3. It was revealed that T3 markedly induced the expression of α isoform but not of β. This T3-mediated increase in the α isoform was associated with a significant decrease in endogenous calcineurin activity. These results suggest that the expression of ZAKI-4 isoforms is subjected to distinct hormonal as well as tissue-specific regulation, constituting a complex signalling network through inhibition of calcineurin.
Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase
Authors: DENG Jing Ti , SUTHERLAND Cindy , BRAUTIGAN David L. , ETO Masumi , WALSH Michael P.
Published: October 2002

Integrin-linked kinase (ILK) has been implicated in Ca2+- independent contraction of smooth muscle via its ability to phosphorylate myosin. We investigated the possibility that this kinase might also phosphorylate and regulate the myosin light-chain phosphatase inhibitor proteins CPI-17 [protein kinase C (PKC)-dependent phosphatase inhibitor of 17kDa] and PHI-1 (phosphatase holoenzyme inhibitor-1), known substrates of PKC. Both phosphatase inhibitors were phosphorylated by ILK in an in-gel kinase assay and in solution. A Thr→Ala mutation at Thr38 of CPI-17 and Thr57 of PHI-1 eliminated phosphorylation by ILK. Phosphopeptide mapping, phospho amino acid analysis and immunoblotting using phospho-specific antibodies indicated that ILK predominantly phosphorylated the site critical for potent inhibition, i.e. Thr38 of CPI-17 or Thr57 of PHI-1. CPI-17 and PHI-1 thiophosphorylated by ILK at Thr38 or Thr57 respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin, whereas the site-specific mutants CPI-17-Thr38Ala and PHI-1-Thr57Ala, treated with ILK under identical conditions, like the untreated wild-type proteins had no effect on the phosphatase. Consistent with these effects, both thiophospho-CPI-17 and -PHI-1 induced Ca2+ sensitization of contraction of Triton X-100-demembranated rat-tail arterial smooth muscle, whereas CPI-17-Thr38Ala and PHI-1-Thr57Ala treated with ILK in the presence of adenosine 5′-[γ-thio]triphosphate failed to evoke a contractile response. We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.
Protein nitration is predominantly mediated by a peroxynitrite-dependent pathway in cultured human leucocytes
Authors: GALIÑANES Manuel , MATATA Bashir M.
Published: October 2002

Protein nitration is a common characteristic of oxidative injury caused by the invasion of leucocytes into inflammatory lesions. Two distinct pathways of nitration of protein tyrosine residues, namely the peroxynitrite (ONOO-)-mediated pathway and another catalysed by the haem-containing peroxidases, have been reported under experimental conditions. However, the contribution of these two pathways in human leucocytes is still controversial. The present study demonstrates that the process of phenolic nitration of proteins in cultured human leucocytes is mainly ONOO--mediated and that it differs between granulocytes and mononuclear cells, depending on the cell compartment and the stimuli. We have also shown that NO induces protein nitration via a ONOO--dependent pathway, whereas NO2-, the NO metabolite, does not increase but decreases nitration in PMA-stimulated leucocytes. The inhibition of myeloperoxidase activity did not reduce protein nitration; on the other hand, the myeloperoxidase inhibitor aminobenzoic hydrazide caused increased nitration, which was mediated by ONOO-. These results suggest that protein nitration is predominantly mediated by a ONOO--dependent pathway in cultured human leucocytes and that the myeloperoxidase-catalysed pathway does not play a significant role in protein nitration.
Involvement of δ-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum
Authors: VARADHARAJAN S. , DHANASEKARAN S. , BONDAY Z.Q. , RANGARAJAN P.N. , PADMANABAN G.
Published: October 2002

The malaria parasite can synthesize haem de novo. In the present study, the expression of the parasite gene for Δ-aminolaevulinate synthase (PfALAS) has been studied by reverse transcriptase PCR analysis of the mRNA, protein expression using antibodies to the recombinant protein expressed in Escherichia coli and assay of ALAS enzyme activity in Plasmodium falciparum in culture. The gene is expressed through all stages of intra-erythrocytic parasite growth, with a small increase during the trophozoite stage. Antibodies to the erythrocyte ALAS do not cross-react with the parasite enzyme and vice versa. The recombinant enzyme activity is inhibited by ethanolamine and the latter inhibits haem synthesis in P. falciparum and growth in culture. The parasite ALAS is localized in the mitochondrion and its import into mitochondria in a cell-free import assay has been demonstrated. The import is blocked by haemin. On the basis of these results, the following conclusions are arrived at: PfALAS has distinct immunological identity and inhibitor specificity and is therefore a drug target. The malaria parasite synthesizes haem through the mitochondrion/cytosol partnership, and this assumes significance in light of the presence of apicoplasts in the parasite that may be capable of independent haem synthesis. The PfALAS gene is functional and vital for parasite haem synthesis and parasite survival.
Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and −insensitive pathways
Authors: KNEBEL Axel , HAYDON Claire E. , MORRICE Nick , COHEN Philip
Published: October 2002

Eukaryotic elongation factor 2 (eEF2) kinase, the enzyme that inactivates eEF2, is controlled by phosphorylation. Previous work showed that stress-activated protein kinase 4 (SAPK4, also called p38Δ) inhibits eEF2 kinase in vitro by phosphorylating Ser-359, while ribosomal protein S6 kinases inhibit eEF2 kinase by phosphorylating Ser-366 [Knebel, Morrice and Cohen (2001) EMBO J. 20, 4360—4369; Wang, Li, Williams, Terada, Alessi and Proud (2001) EMBO J. 20, 4370—4379]. In the present study we have examined the effects of the protein synthesis inhibitor anisomycin and tumour necrosis factor-α (TNF-α) on the phosphorylation of eEF2 kinase. We demonstrate that Ser-359, Ser-366 and two novel sites (Ser-377 and Ser-396) are all phosphorylated in human epithelial KB cells, but only the phosphorylation of Ser-359 and Ser-377 increases in response to these agonists and correlates with the dephosphorylation (activation) of eEF2. Ser-377 is probably a substrate of MAPKAP-K2/K3 (mitogen-activated protein kinase-activated protein kinase 2/kinase 3) in cells, because eEF2 kinase is phosphorylated efficiently by these protein kinases in vitro and phosphorylation of this site, induced by TNF-α and low (but not high) concentrations of anisomycin, is prevented by SB 203580, which inhibits SAPK2a/p38, their ‘upstream’ activator. The phosphorylation of Ser-359 induced by high concentrations of anisomycin is probably catalysed by SAPK4/p38Δ in cells, because no other stress-activated, proline-directed protein kinase tested phosphorylates this site in vitro and phosphorylation is insensitive to SB 203580. Interestingly, the phosphorylation of Ser-359 induced by TNF-α or low concentrations of anisomycin is suppressed by SB 203580, indicating that phosphorylation is also mediated by a novel pathway. Since the phosphorylation of Ser-377 does not inhibit eEF2 kinase in vitro, our results suggest that anisomycin or TNF-α inhibit eEF2 kinase via the phosphorylation of Ser-359.
Protection against exercise‐induced bronchoconstriction by montelukast in aspirin‐sensitive and aspirin‐tolerant patients with asthma
Authors: Mastalerz L. , Gawlewicz‐Mroczka A. ,   E. Nizankowska, Cmiel A. , Szczeklik A.
Published: October 2002

Background Montelukast, a cysteinyl‐leukotriene receptor antagonist, was reported to have a protective effect against exercise‐induced bronchoconstriction (EIB). Aspirin‐induced asthma (AIA) is characterized by overproduction of cysteinyl‐leukotrienes.

Objective The aim of the study was to compare the response to exercise and the effect of montelukast on EIB in AIA as compared to aspirin‐tolerant asthma (ATA).

Methods A placebo‐controlled, double blind, cross‐over randomized study was performed in 19 AIA and 21 ATA patients with stable asthma. A single dose of montelukast (10 mg) or placebo (PL), was given orally one hour prior to exercise challenge. FEV1 was measured before and 5, 10, 15 min after exercise and then at 15‐minute intervals for 4 h. Urinary LTE4 excretion and blood eosinophil count were measured at baseline, 2 h and 4 h following exercise challenge.

Results Positive bronchial response to exercise was observed in 47.5% of all patients studied. Exercise led to almost identical maximal fall in FEV1 in AIA and ATA patients (23.5% ± 6.8% vs. 21.8% ± 12.0%, respectively; P = 0.7). Montelukast, as compared to PL, significantly attenuated EIB in 63.2% of 19 patients with positive exercise test preceded by PL. The mean of maximum fall in FEV1 from the pre‐exercise value was 10.2% ± 13.8 after montelukast as compared to 22.5% ± 10.2 after placebo (P < 0.001). No significant differences between protective effect of montelukast was observed in AIA as compared to ATA patients (P = 0.63, anova). Urinary LTE4 excretion showed no change following exercise, irrespective of the result of the test in all subjects.

Conclusion Patients with AIA and ATA react similarly to exercise challenge and obtain similar protection against EIB by montelukast.
Estimation of projection errors in human ocular fundus imaging
Authors: Doelemeyer Arno , Petrig Benno L.
Published: October 2002

Photogrammetric analysis of features in human ocular fundus images is affected by various sources of errors, for example aberrations of the camera and eye optics. Another—usually disregarded—type of distortion arises from projecting the near spherical shape of the fundus onto a planar imaging device. In this paper we quantify such projection errors based on geometrical analysis of the reduced model eye imaged by a pinhole camera. The projection error found near the edge of a 50° fundus image is 24%. In addition, the influence of axial ametropia is investigated for both myopia and hyperopia. The projection errors found in hyperopia are similar to those in emmetropia, but decrease in myopia. Spherical as well as ellipsoidal eye shapes were used in the above calculation and their effect was compared. Our results suggest that the simple spherical eye shape is sufficient for correcting projection distortions within a range of ametropia from −5 to +5 diopters.
Macular pigment optical density measurement: a novel compact instrument
Authors: Beatty Stephen , Koh Hui‐Hiang , Carden David , Murray Ian J.
Published: October 2002

A compact device to derive the optical density of human macular pigment (MP) using heterochromatic flicker photometry is described. The validity of the system is assessed by measuring the optical density spectra of MP in 12 healthy subjects and comparing this with well‐established previously published values. The mean spectral absorbance characteristics of MP across subjects corresponds well with accepted values. As reported in other studies, our measurements show a wide variation of MP optical densities between individuals. In our technique within‐subject variability is low; standard deviations are between 0.025 and 0.15 in most cases. The overall optical density of MP ranged from 0.08 to 0.84 with a mean of 0.496 and standard deviation of 0.257 at 460 nm. The stimulus size was 0.95 degrees. The unique feature of the technique is that it allows free viewing (not Maxwellian View) of the stimulus, it can be conducted easily and quickly and does not need frequent re‐calibration.
Positive (1→3)‐β‐d‐glucan in blood components and release of (1→3)‐β‐d‐glucan from depth‐type membrane filters for blood processing
Authors: Usami Makoto , Ohata Atsushi , Horiuchi Takeshi , Nagasawa Koichi , Wakabayashi Toshio , Tanaka Shigenori
Published: October 2002

BACKGROUND
: The false‐positive elevation of plasma (1→3)‐β‐
d ‐glucan level, a serodiagnostic test for deep‐seated mycosis, is suspected in patients administered with blood components.

STUDY DESIGN AND METHODS
: (1→3)‐β‐
d
‐Glucan and endotoxin levels in blood components consisting of 12 albumins, 8 immunoglobulins, and 3 blood coagulation factors were measured by fungal infection tests (Fungitec G‐test, Seikagaku Co.; the Wako WB003 test, Wako Pure Chemical Industries; and the Endospec ES test, Seikagaku Co.). In vitro release of (1→3)‐β‐
d
‐glucan from the depth‐type filters made by cellulose membrane to process blood components was analyzed through an in vitro filtration process as a source of (1→3)‐β‐
d ‐glucan in blood components.

RESULTS
: The amounts of (1→3)‐β‐
d
‐glucan in blood components ranged from 0 to 7510 pg per mL in the Fungitec G‐test, with wide variations among brands. The positive rates over 20 pg per mL were 75 percent in albumin solutions, 40 percent in blood coagulation factors, and 63 percent in immunoglobulin solutions. (1→3)‐β‐
d
‐Glucan levels released from the five depth filters ranged from 5 to 2516 pg per mL. The (1→3)‐β‐
d ‐glucan level in filtration fluid was decreased by rinsing with distilled water, but rebounded again during the albumin filtration process.

CONCLUSION
: Depth filters are considered the source of (1→3)‐β‐
d ‐glucan content in some blood components.
Isoimmunization against CD36 (glycoprotein IV): description of four cases of neonatal isoimmune thrombocytopenia and brief review of the literature
Authors: Curtis Brian R. , Ali Saira , Glazier Anne M. , Ebert Douglas D. , Aitman Timothy J. , Aster Richard H.
Published: October 2002

BACKGROUND : Platelet CD36 (glycoprotein [GP] IV) deficiency occurs in 3 to 5 percent of persons of Asian or African ancestry. A subset of these individuals is at risk for immunization against CD36, but the magnitude of this problem and its significance in transfusion medicine have not yet been clarified.

STUDY DESIGN AND METHODS : Clinical and laboratory aspects of neonatal thrombocytopenia involving five infants born to four CD36– mothers were characterized. The CD36 gene was sequenced in three mothers. The literature concerning isoimmunization against CD36 was reviewed and summarized.

RESULTS : Isoantibodies reactive with CD36 on normal platelets and platelets from the fathers were identified in each of the four mothers. Two African‐American mothers were homozygous for a 1264T>G mutation in the CD36 gene. A mother of Italian ancestry was homozygous for a previously unidentified deletion of exons 1 through 3. Previously reported cases of isoimmunization against CD36 were reviewed and summarized.

CONCLUSION : Isoimmunization against CD36 can cause neonatal isoimmune thrombocytopenia (NITP), refractoriness to platelet transfusions, and post‐transfusion purpura. Immunization against this glycoprotein (GP) should be considered in patients with apparent alloimmune platelet disorders not explained by immunization against recognized platelet‐specific alloantigens, especially in persons of African, Asian, and, possibly, Mediterranean ancestry.
Anti‐Vel reactivity diminished by adsorption with rabbit RBC stroma
Authors: Mechanic Steven A. , Maurer Joan L. , Igoe Mark J. , Kavitsky Donna M. , Nance Sandra T.
Published: October 2002

BACKGROUND : An anti‐Vel, nearly missed in antibody identification studies, and the effect of a commercially available rabbit RBC stroma (RESt, Immucor) adsorptions on eight anti‐Vel sera are reported. Anti‐Vel is an antibody to an antigen of high prevalence.

CASE REPORT: A 48‐year‐old woman with chronic vaginal bleeding presented with a Hct of 14.7 percent. The transfusion service was not informed of her history of anti‐Vel when she was transferred from another institution. Studies performed on an emergency request for transfusion were interpreted as a cold autoantibody as adsorption with a commercial source of RESt eliminated the reactivity. Stored anti‐Vel sera were tested by titration studies before and after adsorption with commercial RESt.

RESULTS : Serum from the index case did not react after adsorption with RESt at the transfusion service. Studies with the stored anti‐Vel indicated antibody adsorption with four of four samples at immediate spin (IS) and room temperature (RT) phases, four of eight samples at 37°C in albumin (ALB) phase, and four of eight samples at ALB‐IgG‐AGT phase. Variations in antibody reactivity were observed in the samples tested, but RESt adsorption diminished antibody reactivity in most samples. All eight stored sera demonstrated some reactivity in at least one phase after adsorption with RESt.

CONCLUSION : Anti‐Vel was completely or partially adsorbed by RESt. Caution should be used when interpreting cold agglutinins with this method. The manufacturer warns that uncommon alloantibodies may be adsorbed.
Surgical Management of Constipation
Authors: White RN
Published: October 2002

There are many recognised causes of constipation in the cat and the management of the condition depends on the clinician's ability to recognise the appropriate aetiology in each case. Most surgery therapies for constipation in the cat are related to the management of idiopathic megacolon, although causes such as pelvic outlet obstruction, complications of neutering surgery, perineal herniation, and malunion pelvic fractures may also require surgical intervention. Currently, the surgical management of megacolon consists of subtotal colectomy with the recommendation that the ileocolic junction be preserved. The procedure, in general, is associated with few life-threatening complications although the majority of individuals will experience a transient period of loose stool formation in the immediate post-operative period. In the majority of cases, the long-term outcome following subtotal colectomy is considered excellent.
Genetic polymorphisms of glutathione S‐transferase A1, the major glutathione S‐transferase in human liver: Consequences for enzyme expression and busulfan conjugation
Authors: Bredschneider Monika , Klein Kathrin , Mürdter Thomas E. , Marx Claudia , Eichelbaum Michel , Nüssler Andreas K. , Neuhaus Peter , Zanger Ulrich M. , Schwab Matthias
Published: October 2002

Background

High‐dose busulfan is widely used as part of conditioning regimens for patients who are undergoing hematopoietic stem cell or bone marrow transplantation. High plasma concentrations of busulfan have been linked to the occurrence of hepatic venoocclusive disease (VOD), a severe complication associated with a high mortality. Because conjugation with glutathione, the major route of biotransformation of busulfan, is predominantly catalyzed by the isozyme glutathione S‐transferase A1 (GSTA1), we hypothesized that low expression or function of GSTA1 in liver caused by genetic polymorphisms may be the mechanism underlying VOD.

Methods

Immunoblot analysis of GSTA and measurement of busulfan‐glutathione conjugation by liquid chromatography‐mass spectrometry were performed in 48 normal human liver samples. To search for polymorphisms, the complete GSTA1 coding regions and the promoter fragment were sequenced. All results were compared by multivariate analysis.

Results

Absolute levels of GSTA protein and formation rates of busulfan‐glutathione conjugate displayed a 7‐ and 8‐fold range, from 240 to 1600 pmol/mg and 25 to 205 pmol/min per milligram of total cytosolic protein, respectively, and correlate (r2 = 0.49, P < .0001). A total of 8 single nucleotide polymorphisms (SNPs) of GSTA1 were identified, 1 of which was a silent mutation in exon 5 (A375G); all others were found in the promoter region. Haplotype analysis revealed the existence of 5 defined alleles. There was no significant relationship between any of the GSTA1 SNPs or haplotypes and either hepatic glutathione S‐transferase A (GSTA) expression or GSTA1 function.

Conclusions

The identified GSTA1 polymorphisms are not likely to be related to the VOD because they do not appear to be associated with changes in GSTA expression or function. Compared with other members of the GST family, GSTA1 displays surprisingly little variation.

Clinical Pharmacology & Therapeutics (2002) 71, 479–487; doi: 10.1067/mcp.2002.124518
Bivalirudin pharmacokinetics and pharmacodynamics: Effect of renal function, dose, and gender
Authors: Robson Richard , White Harvey , Aylward Philip , Frampton Christopher
Published: October 2002

Background

These studies were conducted to determine whether bivalirudin clearance and pharmacodynamics are dependent on dose, renal function, or gender.

Methods

Two studies were performed. The first comprised 25 patients who were undergoing percutaneous coronary intervention—8 with normal renal function, 11 with mild renal impairment, and 6 with moderate renal impairment. Each patient received a bolus dose of bivalirudin (1 mg/kg) followed by an infusion (2.5 mg/kg per hour for 4 of 6 hours, then 0.5 mg/kg per hour for 4 of 6 hours). The second study enrolled 8 volunteers with severe renal impairment who received a bivalirudin bolus of 1 mg/kg, followed by an infusion of 0.5 mg/kg per hour for 10 hours. Bivalirudin in plasma and urine was assayed with a newly developed, highly specific liquid chromatography‐mass spectrometry assay.

Results

Clearances at the two infusion doses did not differ significantly (3.23 mL/min per kilogram and 3.16 mL/min per kilogram). There was no statistically significant difference in area under the concentration‐time curve (AUC) and in plasma clearance between patients with normal renal function and those with mild renal impairment. Patients with moderate and severe renal impairment had reductions in plasma clearance of 21% and 24%, respectively. The level of anticoagulation(activated clotting time) was similar between groups. There was no difference between male and female patients.

Conclusion

The clearance of bivalirudin is dependent on renal function but independent of dose and gender. Approximately 20% of unchanged drug is cleared via the kidney, and the remainder presumably undergoes proteolysis intracellularly. The pharmacodynamics of bivalirudin are dose‐dependent and gender‐independent. Bivalirudin kinetics are linear in the dose ranges that are used in percutaneous coronary intervention and that are under investigation for use in acute coronary syndromes.

Clinical Pharmacology & Therapeutics (2002) 71, 433–439; doi: 10.1067/mcp.2002.124522
Religious beliefs of patients and caregivers as a barrier to the pharmacologic control of cancer pain
Authors: Bosch Fèlix , Baños Josep E.
Published: October 2002

Clinical Pharmacology & Therapeutics (2002) 72, 107–111; doi: 10.1067/mcp.2002.126180
Primary Health Care of Survivors of Childhood Sexual Abuse: How Can Psychiatric Nurses Be Helpful?
Authors: Roberts Susan Jo
Published: October 2002

Researchers have demonstrated that 15% to 30% of all women were sexually abused as children. Although information on the emotional; behavioral cognitive, and medical sequelae of this abuse has been available to mental health professionals, problems that abuse survivors experience during routine primary care are less well known. This article discusses the primary care needs of adult survivors of childhood sexual abuse and suggests ways that psychiatric nurses can be helpful in making sure that survivors receive adequate and sensitive primary health care services.
Fluid Group: Concept and Clinical Application in the Therapeutic Milieu
Authors: Echternacht Marcy Rea
Published: October 2002

The term fluid group as used by Gregg (1976) describes an important intervention modality for nurses working in therapeutic milieu settings. Fluid group work is a disciplined application of psychotherapeutic principles, knowledge, and skills to brief, unplanned clinical encounters. Moving into and out of spontaneous interactions with patients in a fluid manner is an important concept and educational strategy that can be used to teach nursing students within the milieu setting.
Students Go to Court: Experiential Learning about Domestic Violence
Authors: Evans Ginger W. , Helton Sally M. , Blackburn Lynn S.
Published: October 2002

A unique educational module focused on domestic violence was developed at a large southeastern university to prepare nurses to deal with the complexities of family violence. This module included experiential learning to capture the full impact of violence, desensitize students to the “stories” of violence, and encourage maturity as the students developed wisdom beyond classroom knowledge. The goals were for students to recognize violence as significant, pervasive, and a long-term problem affecting health, safety, and well-being and to learn interventions appropriate for victims and perpetrators. Data from four semesters indicated a significant increase in knowledge about domestic violence and resources, decreased anxiety, increased confidence, and improvement in communication and assessment skills.
Psychiatric and Geriatric Nurses Together at the Table: Evaluation of a Combined Conference
Authors: Smith Marianne , Buckwalter Kathleen C. , Maxson Ellen
Published: October 2002

Older adults who exhibit behavioral symptoms, particularly aggression, are increasingly being admitted from long-term care settings to psychiatric units for evaluation and treatment. Posthospitalization “success” is often limited, suggesting that improved understanding and communication between nurses who work in nursing homes and those who work in hospital inpatient units may be needed. With use of a video about older adults and aggression as a basis for education, discussion, and interaction, geriatric/long-term care and psychiatric nurses participated in a day-long program. The conference was designed to bring the two groups together to focus on common problems and solutions, sharing information, and networking. Quantitative evaluation, including 15 items that rated the relevance, usefulness, and overall quality of the program and teaching approaches, and qualitative evaluation in the form of narrative comments about the program’s most and least useful aspects, support the value of the approach.
Behavioral Management of Persistent Auditory Hallucinations in Schizophrenia: Outcomes from a 10-Week Course
Authors: Trygstad Louise , Buccheri Robin , Dowling Glenna , Zind Roberta , White Kathy , Griffin Jan Johnson , Henderson Susan , Suciu Lynda , Hippe Susan , Kaas Merrie J. , Covert Cheryl , Hebert Patrice
Published: October 2002

BACKGROUND: Medication-resistant, persistent auditory hallucinations are pervasive in persons with schizophrenia. Behavior strategies are often very effective as adjunctive therapy to decrease the negative characteristics of this symptom.

OBJECTIVES: The purpose of this multi-site intervention study was to examine the short-term effects of a 10-week course to teach behavior management of persistent auditory hallucinations on seven characteristics of auditory hallucinations (i.e., frequency, loudness, self-control, clarity, tone, distractibility, and distress), anxiety, and depression.

STUDY DESIGN: A quasi-experimental repeated measured design was used. The sample included 62 outpatients with schizophrenia who reported daily persistent auditory hallucinations. Measures included the Characteristics of Auditory Hallucinations Questionnaire, the tension-anxiety subscale of the Profile of Mood States, and the Beck Depression Inventory II.

RESULTS: Preintervention scores for the frequency (p < .001), self-control (p < .03), clarity (p < .01), tone (p < .03), distractibility (p < .006), and distress (p < .001) improved compared with preintervention scores. Postintervention scores on anxiety and depression were also significantly lower than preintervention scores (p < .02, p < .001, respectively).

CONCLUSIONS: Teaching behavior management of persistent auditory hallucinations in a standardized 10-week course is clinically effective and can be incorporated into many existing outpatient programs.
Perceived Social Support: Dimensions of Social Interaction among Sober Female Participants in Alcoholics Anonymous
Authors: Rush Mary M.
Published: October 2002

BACKGROUND: Dimensions of perceived group, perceived personal, and overall perceived social support were examined among 125 sober female members of Alcoholics Anonymous (AA).

STUDY DESIGN: This was an exploratory, correlational study using the Social Support Network Inventory (SSNI).

RESULTS: Of the SSNI’s 5 dimensions (available, practical, emotional, reciprocal, and sobriety-related social support), reciprocal support was the strongest contributor to group social support. Those women who had a sponsor scored significantly higher in total social support and personal support. Availability was the strongest contributor to both personal and overall perceived social support.

CONCLUSIONS: Availability and sponsorship are important components of a supportive environment among women in sobriety.
Transgenic overexpression of the sarcoplasmic reticulum Ca2+ ATPase improves reticular Ca2+ handling in normal and diabetic rat hearts
Authors: Vetter Roland , Rehfeld Uwe , Reissfelder Christoph , Weiß Wolfgang , Wagner Kay‐Dietrich , Günther Joachim , Hammes Annette , Tschöpe Carsten , Dillmann Wolfgang , Paul Martin
Published: October 2002

Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca2+‐ATPase SERCA2a. To evaluate the impact of SERCA2a overexpression on SR Ca2+ handling in diabetic CM, we 1) generated transgenic rats harboring a human cytomegalovirus enhancer/chicken β‐actin promotor‐controlled rat SERCA2 transgene (SERCA2‐TGR), 2) characterized their SR phenotype, and 3) examined whether transgene expression may rescue SR Ca2+ transport in streptozotocin‐induced diabetes. The transgene was expressed in all heart chambers. Compared to wild‐type (WT) rats, a heterozygous line exhibited increased SERCA2 mRNA (1.5‐fold), SERCA2 protein (+26%) and SR Ca2+ uptake (+37%). Phospholamban expression was not altered. In SERCA2‐TGR, contraction amplitude (+48%) and rates of contraction (+34%) and relaxation (+35%) of isolated papillary muscles (PM) were increased (P<0.05 vs. WT, respectively); the lusitropic and inotropic responses of PM to forskolin were stronger than in WT. In diabetic myocardium with SR dysfunction, Ca2+ uptake and SERCA2 protein of SERCA2‐TGR were 1.3‐fold higher (P<0.05 vs. diabetic WT). Thus, a SERCA2 overexpression in rat heart improves Ca2+ uptake, accelerates relaxation and compensates, in part, for depressed Ca2+ uptake in diabetic CM. Therefore, SERCA2 expression might constitute an important therapeutic target to rescue cardiac SR Ca2+ handling in diabetes.
A consumer‐driven model for mass customization in the apparel market
Authors: Jo Anderson‐Connell Lenda , Ulrich Pamela V. , Brannon Evelyn L.
Published: October 2002

The overall purpose of this research was to explore the potential for applying mass customization in the apparel manufacturing and retail sectors by investigating consumers’ interests in it as a concept. A series of seven focus groups were used to explore consumer preferences related to mass customization and to identify potential barriers to adoption of the concept. Potential scenarios illustrated with video were used to describe how mass customization might be implemented. A deductive approach to data reduction allowed researchers to distill and describe data according to predetermined categories and to identify additional categories that emerged in the analysis. Converging positive consumer comments moved researchers forward in understanding the concept while negative comments were viewed as barriers. The result was the construction of a consumer‐based model which provides an initial framework for researchers and the business community to use in exploring how the paradigm of mass customization could be applied as a business strategy in the apparel industry.
Multi‐script bibliographic database: an Indian perspective
Authors: Chandrakar Rajesh
Published: October 2002

In this Internet era, when everything is going on the Web, character encoding becomes an issue for developers and facilitators. This matter also concerns India, as a country with rich diversity in languages, cultures, customs and religions, which are stored in print media as manuscripts, monographs, pamphlet, tamra‐patras (copper plates), palm leaves etc. Library and information networks in India hold the responsibility to digitise all those valuable resources stored in print media and make them accessible to users through the Web. However, due to technology limitations, so far it has not been practical to do so. This paper tries to explain the limitations and problems being faced in this regard, highlights the issues involved with multi‐script database creation and the required state‐of‐the‐art technology. Finally, Unicode is considered as a solution as it is a Universal Character Set for character encoding.
Implicit and Self‐Attributed Achievement Motives: Concordance and Predictive Validity
Authors: Thrash Todd M. , Elliot Andrew J.
Published: October 2002

ABSTRACT As a complement to the literature on the discriminant validity of implicit and self‐attributed motives, this study explored two issues that point to convergences: moderation of concordance between implicit and self‐attributed achievement motives, and the role of the two types of motive as antecedents of achievement goals. Significant positive correlations were found between implicit and self‐attributed need for achievement and between implicit and self‐attributed fear of failure. Individuals higher in self‐determination were more concordant in implicit and self‐attributed need for achievement. Implicit and self‐attributed achievement motives predicted achievement goals in a similar manner, and structural equation modeling yielded good fit for a conceptually parsimonious latent motive model. It is suggested that implicit and self‐attributed motives converge in some respects (yet diverge in others), and implications for theory are discussed.
Carbon Monoxide Cycling by
Desulfovibrio vulgaris
Hildenborough
Authors: Voordouw Gerrit
Published: October 2002

Sulfate-reducing bacteria, like
Desulfovibrio vulgaris
Hildenborough, use the reduction of sulfate as a sink for electrons liberated in oxidation reactions of organic substrates. The rate of the latter exceeds that of sulfate reduction at the onset of growth, causing a temporary accumulation of hydrogen and other fermentation products (the hydrogen or fermentation burst). In addition to hydrogen,
D. vulgaris
was found to produce significant amounts of carbon monoxide during the fermentation burst. With excess sulfate, the
hyd
mutant (lacking periplasmic Fe-only hydrogenase) and
hmc
mutant (lacking the membrane-bound, electron-transporting Hmc complex) strains produced increased amounts of hydrogen from lactate and formate compared to wild-type
D. vulgaris
during the fermentation burst. Both hydrogen and CO were produced from pyruvate, with the
hyd
mutant producing the largest transient amounts of CO. When grown with lactate and excess sulfate, the
hyd
mutant also exhibited a temporary pause in sulfate reduction at the start of stationary phase, resulting in production of 600 ppm of headspace hydrogen and 6,000 ppm of CO, which disappeared when sulfate reduction resumed. Cultures with an excess of the organic electron donor showed production of large amounts of hydrogen, but no CO, from lactate. Pyruvate fermentation was diverse, with the
hmc
mutant producing 75,000 ppm of hydrogen, the
hyd
mutant producing 4,000 ppm of CO, and the wild-type strain producing no significant amount of either as a fermentation end product. The wild type was most active in transient production of an organic acid intermediate, tentatively identified as fumarate, indicating increased formation of organic fermentation end products in the wild-type strain. These results suggest that alternative routes for pyruvate fermentation resulting in production of hydrogen or CO exist in
D. vulgaris
. The CO produced can be reoxidized through a CO dehydrogenase, the presence of which is indicated in the genome sequence.
Characterization of Dryas octopetala ectomycorrhizas from limestone karst vegetation, western Ireland
Authors: Harrington Thomas J , Mitchell Derek T
Published: October 2002

The principal ectomycorrhizas of Dryas octopetala L. from a treeless grass-heath in the Burren, western Ireland, were characterized using morphotyping and molecular methods (PCR-RFLP analysis of ITS-rDNA and sequencing of the ITS region). Twenty-one distinct morphotypes are described. Six of these (Cortinarius atrovirens Kalchbr., Cortinarius caesiocanescens (Mos.) Kühn. & Romagn., Cortinarius calochrous (Mos.) Nezd., Cortinarius odorifer Britz., Cortinarius mussivus Fr., and Tricholoma myomyces (Scop.) Quél.) were distinguished by tracing rhizomorph connections between mycorrhizas and basidiomes. The ectomycorrhizas of Cenococcum geophilum Fr., Craterellus lutescens (Pers.:Fr.) Fr., and Hebeloma sinapizans (Paulet:Fr.) Gill were identified based on molecular and morphological evidence. The ectomycorrhizas of Cortinarius brunneus (Pers.:Fr.) Fr., Cortinarius infractus (Pers.:Fr.) Fr., Hydnum repandum L., and Hebeloma circinans Quél. were distinguished provisionally, because they were consistently found in soil core samples containing basidiomes of a particular fungal species. The provisional identification of Lactarius sanguifluus (Paulet) Fr., and Russula delica Fr. ectomycorrhizas was also based on anatomical evidence, particularly the presence of lacticifers and cystidia, respectively. Six morphotypes could not be assigned to a specific fungal taxon and, therefore, were named "Dryadirhiza" + a characterizing epithet (D. aerea, D. cerina, D. fulgens, D. nigra, D. rugosa, and D. truncata). It is concluded that Dryas octopetala forms ectomycorrhizal associations in the Burren with woodland fungal species.Key words: ectomycorrhizas, Dryas octopetala, morphotyping, ITS-RFLP, mountain avens.
Large deviations for a Markov chain in a random landscape
Authors: Guillotin-Plantard Nadine
Published: October 2002

Let (Sk)k≥0be a Markov chain with state spaceEand (ξx)x∊Ebe a family of ℝp-valued random vectors assumed independent of the Markov chain. The ξxcould be assumed independent and identically distributed or could be Gaussian with reasonable correlations. We study the large deviations of the sum
Prediction of liner wear by extending the Kragelskii model for wear of roughness peaks in sparse contact
Authors: Lakshminarayanan P. A. , Nayak N , Dani A. D.
Published: October 2002

The known wear model of Kragelskii for surfaces considers elastic loading of the normal roughness peaks in sparse contact by the shear load along the direction of sliding. Repeated stressing of the peaks causes fatigue to detach material in the form of wear debris. In this paper, an attempt is successfully made to predict the wear of cylinder liners of wide-ranging surface finishes and material strengths, by extending the model to take into account surfaces that do not have normally peaked roughness. The roughness peaks are modelled as tiny hemispheres. The radius of the hemisphere is defined as the geometric mean of the radii in the directions transverse and longitudinal to machining. The transverse radius can be estimated using the actual roughness trace. An alternative and quicker method is presented here to derive this radius as a function of the number of roughness peaks per unit length, the peak roughness, Rp k, and the fraction of the bearing surface MR 1 at Rp k. The latter radius along the machining direction is typical of the machining process.

The wear rate of a normal finish is known to be a strong function of the maximum deviation of the roughness trace from the mean line, Rp. The valley portion of roughness, R vk, does not take part in wear as actively as the roughness parameter, R k, lying between Rvk and Rpk. A general surface roughness, which is not normally peaked, is characterized by the plateauness ratio, R k/ Rvk. In the present work, an equivalent roughness Rp-eq for such a general surface is found to bear a unique relation with the plateauness ratio.

To study surfaces of general roughness, the equivalent Rp-eq and the radius of the hemispherical roughness peak were substituted in the wear model known for surfaces with normal roughness. Ten different liner surfaces reported in the literature were studied using the present model. In addition, experiments were conducted on a 105mm bore diesel engine using normally honed liners to apply the wear model. A satisfactory correlation was obtained between the predicted wear rates and those measured with the model. Finally, the results are discussed in the light of wear predicted by Archard [3, 11].