bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of postnatal development of heart rate responses to trigeminal stimulation in sleeping preterm and term infants
Authors: TULADHAR RITA , HARDING RICHARD , MICHAEL ADAMSON T. , HORNE ROSEMARY S. C.
Published: March 2005

Autonomic dysfunction has been regarded as a possible cause of the sudden infant death syndrome (SIDS) and it has been suggested that preterm infants, who are at a greater risk of SIDS than term infants, may have immature autonomic control. Our aim was to compare the maturation of cardiac autonomic control during sleep in preterm and term infants by examining heart rate responses to arousing and non‐arousing trigeminal stimuli. Preterm infants (n = 15) and term infants (n = 24) were studied longitudinally with daytime polysomnography. Air‐jet stimulation of the nares was delivered in both active sleep (AS) and quiet sleep (QS), and heart rate (HR) changes recorded for both arousal and non‐arousal responses. Changes in HR (ΔHR%) were calculated as the relative differences between baseline HR (BHR) and either MaxHR (arousal) or MinHR (non‐arousal). Comparisons of HR changes between sleep states and postnatal ages were made with two‐way anova for repeated measures and between groups with two‐way anova. The increase in HR (ΔHR%) was greater in term than preterm infants (P < 0.05), but only at 2–3 weeks corrected postnatal age (CPA). In preterm infants, there were no differences in BHR between sleep states, whereas in term infants, BHR was higher in AS than in QS at 2–3 weeks and 2–3 months of age. The smaller ΔHR% to arousing stimuli in preterm infants compared with term infants at 2–3 weeks suggests that cardiac sympathetic activity in preterm infants may be lower than in term infants. This mechanism may account for the increased risk for SIDS of preterm infants.
Impaired alertness and performance driving home from the night shift: a driving simulator study
Authors: ÅKERSTEDT TORBJÖRN , PETERS BJÖRN , ANUND ANNA , KECKLUND GÖRAN
Published: March 2005

Driving in the early morning is associated with increased accident risk affecting not only professional drivers but also those who commute to work. The present study used a driving simulator to investigate the effects of driving home from a night shift. Ten shift workers participated after a normal night shift and after a normal night sleep. The results showed that driving home from the night shift was associated with an increased number of incidents (two wheels outside the lane marking, from 2.4 to 7.6 times), decreased time to first accident, increased lateral deviation (from 18 to 43 cm), increased eye closure duration (0.102 to 0.143 s), and increased subjective sleepiness. The results indicate severe postnight shift effects on sleepiness and driving performance.
Less effective executive functioning after one night's sleep deprivation
Authors: NILSSON JENS P. , SÖDERSTRÖM MARIE , KARLSSON ANDREAS U. , LEKANDER MATS , ÅKERSTEDT TORBJÖRN , LINDROTH NINA ERIXON , AXELSSON JOHN
Published: March 2005

The prefrontal cortex (PFC) is affected negatively by sleep deprivation (SD) and executive functioning is largely dependent on activity in the PFC. Earlier studies have focused on subsystems of executive functioning, and tests of executive functioning have shown both low reliability and low validity. In the present study, 11 healthy volunteers were sleep deprived and compared with 11 healthy controls in a study on effects of one night's SD on integrative executive functioning. Following SD, the performance of subjects on an ecologically valid test, the modified Six Elements Test, was significantly impaired. There were no group differences on psychomotor vigilance, verbal or visuo‐spatial working memory. This extends previous knowledge of performance effects of SD, and may be of special importance for individuals with cognitive work tasks.
The conserved Xanthomonas campestris pv. vesicatoria effector protein XopX is a virulence factor and suppresses host defense in Nicotiana benthamiana
Authors: Metz Matthew , Dahlbeck Douglas , Morales Christina Q. , Sady Bassem Al , Clark Eszter T. , Staskawicz Brian J.
Published: March 2005

Nicotiana benthamiana leaves display a visible plant cell death response when infiltrated with a high titer inoculum of the non‐host pathogen, Xanthomonas campestris pv. vesicatoria (Xcv). This visual phenotype was used to identify overlapping cosmid clones from a genomic cosmid library constructed from the Xcv strain, GM98‐38. Individual cosmid clones from the Xcv library were conjugated into X. campestris pv. campestris (Xcc) and exconjugants were scored for an altered visual high titer inoculation response in N. benthamiana. The molecular characterization of the cosmid clones revealed that they contained a novel gene, xopX, that encodes a 74‐kDa type III secretion system (TTSS) effector protein. Agrobacterium‐mediated transient expression of XopX in N. benthamiana did not elicit the plant cell death response although detectable XopX protein was produced. Interestingly, the plant cell death response occurred when the xopX Agrobacterium‐mediated transient expression construct was co‐inoculated with strains of either XcvΔxopX or Xcc, both lacking xopX. The co‐inoculation complementation of the plant cell death response also depends on whether the Xanthomonas strains contain an active TTSS. Transgenic 35S‐xopX‐expressing N. benthamiana plants also have the visible plant cell death response when inoculated with the non‐xopX‐expressing strains XcvΔxopX and Xcc. Unexpectedly, transgenic 35S‐xopX N. benthamiana plants displayed enhanced susceptibility to bacterial growth of Xcc as well as other non‐xopX‐expressing Xanthomonas and Pseudomonas strains. This result is also consistent with the increase in bacterial growth on wild type N. benthamiana plants observed for Xcc when XopX is expressed in trans. Furthermore, XopX contributes to the virulence of Xcv on host pepper (Capsicum annuum) and tomato (Lycopersicum esculentum) plants. We propose that the XopX bacterial effector protein targets basic innate immunity in plants, resulting in enhanced plant disease susceptibility.
Stable two‐element control of dTph1 transposition in mutator strains of Petunia by an inactive ACT1 introgression from a wild species
Authors: Stuurman Jeroen , Kuhlemeier Cris
Published: March 2005

The high copy dTph1 transposon system of Petunia (Solanaceae) is one of the most powerful insertion mutagens in plants, but its activity cannot be controlled in the commonly used mutator strains. We analysed the regulation of dTph1 activity by QTL analysis in recombinant inbred lines of the mutator strain W138 and a wild species (P. integrifolia spp. inflata). Two genetic factors were identified that control dTph1 transposition. One corresponded to the ACT1 locus on chromosome I. A second, previously undescribed locus ACT2 mapped on chromosome V. As a 6‐cM introgression in W138, the P. i. inflata act1S6 allele behaved as a single recessive locus that fully eliminated transposition of all dTph1 elements in all stages of plant development and in a heritable fashion. Weak dTph1 activity was restored in act1S6/ACT2S6 double introgression lines, indicating that the P. i. inflata allele at ACT2 conferred a low level of transposition. Thus, the act1S6 allele is useful for simple and predictable control of transposition of the entire dTph1 family when introgressed into an ultra‐high copy W138 mutator strain. We demonstrate the use of the ACT1W138/act1S6 allele pair in a two‐element dTph1 transposition system by producing 10 000 unique and fixed dTph1 insertions in a population of 1250 co‐isogenic lines. This Petunia system produces the highest per plant insertion number of any known two‐element system, providing a powerful and logistically simple tool for transposon mutagenesis of qualitative as well as quantitative traits.
pOp6/LhGR: a stringently regulated and highly responsive dexamethasone‐inducible gene expression system for tobacco
Authors: Samalova Marketa , Brzobohaty Bretislav , Moore Ian
Published: March 2005

We describe pOp/LhGR, a dexamethasone‐inducible derivative of the pOp/LhG4 transcription activation system, and its use in tobacco to regulate expression of uidA (encoding β‐glucuronidase; GUS) and the cytokinin‐biosnythetic gene ipt. The pOp/LhGR system exhibited stringent regulation and strong induced phenotypes in soil and tissue culture. In conjunction with an improved target promoter, pOp6, that carries six copies of an optimized lac operator sequence the pOp6/LhGR system directed induced GUS activities that exceeded those obtained with pOp/LhG4 or the CaMV 35S promoter but without increased uninduced activity. A single dose of dexamethasone was sufficient to direct cytotoxic levels of ipt expression in soil‐grown plants although uninduced plants grew normally throughout a complete life cycle. In vitro, induced transcripts were detectable within an hour of dexamethasone application and 1 nm dexamethasone was sufficient for half maximal induction of GUS activity. Various methods of dexamethasone application were successfully applied under tissue culture and greenhouse conditions. We observed no inhibitory effects of dexamethasone or LhGR on plant development even with the highest concentrations of inducer, although tobacco seedlings were adversely affected by ethanol used as a solvent for dexamethasone stock solutions. The pOp/LhGR system provides a highly sensitive, efficient, and tightly regulated chemically inducible transgene expression system for tobacco plants.
New pOp/LhG4 vectors for stringent glucocorticoid‐dependent transgene expression in Arabidopsis
Authors: Craft Judith , Samalova Marketa , Baroux Celia , Townley Helen , Martinez Alberto , Jepson Ian , Tsiantis Miltos , Moore Ian
Published: March 2005

To facilitate glucocorticoid‐inducible transgene expression from the pOp promoter in Arabidopsis the ligand‐binding domain of a rat glucocorticoid receptor (GR LBD) was fused to the amino terminus of the synthetic transcription factor LhG4 to generate LhGR‐N. Fusions bearing the GR LBD at other positions in LhG4 exhibited incomplete repression or inefficient induction. LhGR‐N was stringently repressed in the absence of exogenous glucocorticoid but was fully activated by addition of 2 μm dexamethasone which resulted in 1000‐fold increase in GUS reporter activity. Half maximal induction was achieved with 0.2 μm dexamethasone. Reporter transcripts were detectable within 2 h of dexamethasone application and peaked 4–10 h later. Neither LhGR‐N nor dexamethasone affected seedling development although ethanol retarded development when used as a solvent for dexamethasone. The efficiency of the pOp target promoter was improved 10‐ to 20‐fold by incorporating six copies of the ideal lac operator with sufficient inter‐operator spacing to allow simultaneous occupancy. Introduction of the TMV Ω sequence into the 5′UTR resulted in a further 10‐fold increase in dexamethasone‐inducible reporter activity and an increase in the induction factor to 104. Although promoters containing the TMV Ω sequence exhibited slightly increased basal expression levels in the absence of dexamethasone, stringent regulation of the cytokinin biosynthetic gene ipt was achieved with all promoters. Despite the severity of the induced ipt phenotypes, transcripts for the KNOX homoeodomain transcription factors BREVIPEDICELLUS and SHOOTMERISTEMLESS were not significantly increased within 48 h of dexamethasone application to seedlings.
Senescence‐associated vacuoles with intense proteolytic activity develop in leaves of Arabidopsis and soybean
Authors: Otegui Marisa S. , Noh Yoo‐Sun , Martínez Dana E. , Vila Petroff Martin G. , Andrew Staehelin L. , Amasino Richard M. , Guiamet Juan J.
Published: March 2005

Vacuolar compartments associated with leaf senescence and the subcellular localization of the senescence‐specific cysteine‐protease SAG12 (senescence‐associated gene 12) were studied using specific fluorescent markers, the expression of reporter genes, and the analysis of high‐pressure frozen/freeze‐substituted samples. Senescence‐associated vacuoles (SAVs) with intense proteolytic activity develop in the peripheral cytoplasm of mesophyll and guard cells in Arabidopsis and soybean. The vacuolar identity of these compartments was confirmed by immunolabeling with specific antibody markers. SAVs and the central vacuole differ in their acidity and tonoplast composition: SAVs are more acidic than the central vacuole and, whereas the tonoplast of central vacuoles is highly enriched in γ‐TIP (tonoplast intrinsic protein), the tonoplast of SAVs lacks this aquaporin. The expression of a SAG12‐GFP fusion protein in transgenic Arabidopsis plants shows that SAG12 localizes to SAVs. The analysis of ProSAG12:GUS transgenic plants indicates that SAG12 expression in senescing leaves is restricted to SAV‐containing cells, for example, mesophyll and guard cells. A homozygous sag12 Arabidopsis mutant develops SAVs and does not show any visually detectable phenotypical alteration during senescence, indicating that SAG12 is not required either for SAV formation or for progression of visual symptoms of senescence. The presence of two types of vacuoles in senescing leaves could provide different lytic compartments for the dismantling of specific cellular components. The possible origin and functions of SAVs during leaf senescence are discussed.
Large‐scale screening of Arabidopsis enhancer‐trap lines for seed germination‐associated genes
Authors: Liu Po‐Pu , Koizuka Nobuya , Homrichhausen Tanja M. , Hewitt Jessica R. , Martin Ruth C. , Nonogaki Hiroyuki
Published: March 2005

Enhancer trap is a powerful approach for identifying tissue‐ and stage‐specific gene expression in plants and animals. For Arabidopsis research, β‐glucuronidase (GUS) enhancer‐trap lines have been created and successfully used to identify tissue‐specific gene expression in many plant organs. However, limited applications of these lines for seed germination research have been reported. This is probably due to the impermeability of the testa to the GUS substrate. By focusing on the stages between testa and endosperm rupture, we were able to circumvent the testa barrier to the GUS substrate and observe diverse tissue‐specific gene expression during germination sensu stricto. One hundred and twenty‐one positive subpools of 10 lines out of 1130 were isolated. Approximately 4500 plants from these subpools were grown in a greenhouse and one to seven individual plants exhibiting GUS expression in seeds were isolated for each subpool. This library of the Arabidopsis seed enhancer‐trap lines is an efficient tool for identifying seed germination‐associated genes. The individual lines from this library will be provided to the international seed biology research community. International collaboration to identify the trapped genes using genome‐walking PCR and to characterize the gene functions using knockout plants will significantly enhance our understanding of the molecular mechanisms of seed germination.
Endosomal proteases facilitate the fusion of endosomes with vacuoles at the final step of the endocytotic pathway
Authors: Yamada Kenji , Fuji Kentaro , Shimada Tomoo , Nishimura Mikio , Hara‐Nishimura Ikuko
Published: March 2005

The mechanism by which plasma membrane proteins are transported to vacuoles for degradation has not been well characterized in plants. To clarify how plasma membrane proteins are degraded, we monitored the endocytotic pathway in tobacco suspension‐cultured BY‐2 cells with a fluorescent endocytosis marker, FM4‐64. Because of the efficient and rapid delivery of endosomes to the vacuoles, endosomes were scarcely detectable. Interestingly, we found that E‐64d, an inhibitor of papain family proteases, caused the accumulation of a large number of endosomes in the cells under the sucrose‐starved condition. This result indicates that E‐64d attenuates the fusion of endosomes with vacuoles. We identified two papain homologues, which are localized in the endosomes, with a biotinylated inhibitor. We designated them as endosome‐localized papains (ENPs). Immunofluorescent analysis revealed that vacuolar sorting receptor, a marker of prevacuolar compartment (PVC), was localized in the endosomes. This result and their acidic nature show that the endosomes correspond to PVC. These results suggest that ENPs facilitate the final step in the vacuolar trafficking pathway under the sucrose‐starved condition. We further examined the effects of E‐64d on two transgenic Arabidopsis plants that constitutively express a fusion protein composed of green fluorescent protein (GFP) and a plasma membrane protein (GFP‐PIP2a or GFP‐LTI6b). GFP fluorescence was observed on the plasma membrane of root cells in these transgenic plants. Treatment with E‐64d induced the accumulation of GFP‐fluorescent endosomes and inhibited the degradation of these fusion proteins. No GFP fluorescence was observed in vacuoles in E‐64d‐treated transgenic plants. Taken together, these results suggest that endosomal proteases are required for the fusion of endosomes with vacuoles at the final step in the endocytotic pathway for degradation of plasma membrane proteins in plants.
The stability of the Arabidopsis transcriptome in transgenic plants expressing the marker genes nptII and uidA
Authors: Ouakfaoui Souad El , Miki Brian
Published: March 2005

The ATH1 Arabidopsis GeneChip from Affymetrix was used to search for transcriptome changes in Arabidopsis associated with the strong expression of transgenes regulated by constitutive promoters. The insertion and expression of the commonly used marker genes, uidA and nptII, did not induce changes to the expression patterns of the approximately 24 000 genes that were screened under optimal growth conditions and under physiological stress imposed by low temperatures. Approximately 8000 genes (35% of the Arabidopsis genome) underwent changes in gene expression in both wild‐type and transgenic plants under abiotic stresses such as salt, dehydration, cold, and heat. This study provides detailed information on the extent of non‐targeted or pleiotropic effects of transgenes on plants and shows that the transgenic and non‐transgenic plants were equivalent in their global patterns of transcription. This information may help to extend our understanding and interpretation of the principle of substantial equivalence which is used as a first step in the biosafety evaluation of transgenic crops.
Moisturizing effects of topical nicotinamide on atopic dry skin
Authors: Soma Yoshinao , Kashima Masato , Imaizumi Akiko , Takahama Hideto , Kawakami Tamihiro , Mizoguchi Masako
Published: March 2005

Background  Certain moisturizers can improve skin barrier function in atopic dermatitis. The effect of topical nicotinamide on atopic dry skin is unknown. We examined the effect of topical nicotinamide on atopic dry skin and compared the results with the effect of white petrolatum in a left–right comparison study.

Methods  Twenty‐eight patients with atopic dermatitis, with symmetrical lesions of dry skin on both forearms, were enrolled, and were instructed to apply nicotinamide cream containing 2% nicotinamide on the left forearm and white petrolatum on the right forearm, twice daily over a 4‐ or 8‐week treatment period. Transepidermal water loss and stratum corneum hydration were measured by instrumental devices. The amount of the stratum corneum exfoliated by tape stripping (desquamation index) was determined by an image analyzer.

Results  Nicotinamide significantly decreased transepidermal water loss, but white petrolatum did not show any significant effect. Both nicotinamide and white petrolatum increased stratum corneum hydration, but nicotinamide was significantly more effective than white petrolatum. The desquamation index was positively correlated with stratum corneum hydration at baseline and gradually increased in the nicotinamide group, but not in the white petrolatum group.

Conclusions  Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis.
Effects of mycophenolate mofetil on donor‐specific antibody formation in renal transplantation
Authors: Lederer Stephan R , Friedrich Nicole , Banas Bernhard , von Welser Georg , Albert Ekkehard D , Sitter Thomas
Published: March 2005

Abstract:  Background:  Mycophenolate mofetil (MMF) is a routinely used immunosuppressive agent that selectively blocks T‐ and B‐lymphocyte proliferation. The present study was designed to investigate the effects of this drug on human leukocyte(HLA) antibody production in general and donor‐specific antibody (DSA) formation in particular in 154 recipients of renal allografts.

Patients and methods:  Renal allograft recipients were subdivided into three groups. Group 1 patients (n = 60) had received MMF since transplantation in combination with either cyclosporin A or tacrolimus and steroids. Group 2 patients (n = 29) had received an MMF‐free immunosuppressive regimen initially followed by addition of MMF some time later. Group 3 patients (n = 65) had received no MMF. Cyclosporin A or tacrolimus in combination with azathioprine and/or steroids were used for immunosuppression. DSA were demonstrated by enzyme‐linked immunosorbent assay (ELISA) for detection of panel‐reactive antibodies of HLA class I and II specificity.

Results:  The HLA antibodies were found in 16.7%, 27.6% and 30.8% of transplant recipients in groups 1, 2 and 3, respectively. DSA were found in 8.3%, 17.2% and 20.0%, and non‐DSA in 10.0%, 20.7% and 24.6%, of patients in groups 1, 2 and 3, respectively.

Conclusion:  The MMF reduces anti‐HLA class I and II antibody production and consequently DSA production in renal allograft recipients. Our data indicate this effect to be more pronounced in patients given MMF immediately after transplantation than in those in whom MMF is introduced some time later. The presence of DSA in the serum of renal allograft recipients is associated with poorer graft function (higher serum creatinine and more rejection episodes).
Rapamycin in patients with chronic renal allograft dysfunction
Authors: Wu Mai‐Szu , Chang Chiz‐Tzung , Hung Cheng‐Chieh
Published: March 2005

Abstract:  Purpose:  Nephrotoxicity of calcineurin inhibitors (CNI) complicates the management of chronic renal allograft dysfunction. Rapamycin is a promising immunosuppressive agent free of nephrotoxicity. The effect of conversion from CNI to rapamycin in recipients with chronic allograft dysfunction is still unclear. We investigated the effect of rapamycin in patients with chronic allograft dysfunction.

Methods:  We conducted a prospective study on kidney transplant recipients with chronic allograft dysfunction. The patients were under classic CNI, mycophenolate mofetil, and prednisolone triple therapy. They had progressive deterioration of the allograft function. They were converted from CNI to rapamycin directly and observed for 6 months. The CNI serum levels before the conversion were within recommended range. Allograft function, clinical features and adverse effects were evaluated before and after the rapamycin conversion.

Results:  A total of 16 patients were enrolled. Six of them (37.5%) failed to have a smooth conversion because of deterioration of allograft function and intractable adverse effects. Ten patients (62.5%) went through the 6‐month observation period with improved graft function. The average reduction of serum creatinine was 27.7% (p < 0.001) in successful conversion. There were no significant differences on age, gender, lipid profile, sugar control, and rapamycin levels between successful and failed conversion. Anemia and diastolic blood pressure were significantly improved after successful conversion. The failed patients had a longer transplantation period (6.1 ± 4.1 vs. 11.2 ± 3.4 yr, p < 0.05). Two of them (12.5%) developed bacteria pneumonia. Self‐limited diarrhea developed in three patients (18.8%).

Conclusion:  We suggested that conversion from CNI to rapamycin was beneficial in some kidney transplant recipients with chronic allograft dysfunction.
Gastrointestinal hemorrhage due to complicated gastroduodenal ulcer disease in liver transplant patients taking sirolimus
Authors: Smith Alastair D , Bai Diane , Marroquin Carlos E , Tuttle‐Newhall Janet E , Desai Dev M , Collins Bradley H , Muir Andrew , Kuo Paul C , McHutchison John , Rockey Don C
Published: March 2005

Abstract:  Sirolimus is emerging as a popular immunosuppressive agent for patients undergoing solid organ and pancreatic cell transplantation. Here, we report the clinical courses of three patients receiving sirolimus who developed aggressive gastroduodenal ulcer disease. One patient died from massive gastrointestinal bleeding, and ulcers in the other two patients healed only after discontinuation of sirolimus. We propose that the mechanism underlying this severe ulcer diathesis, and poor ulcer healing, was linked to the well‐known inhibitory effects of sirolimus on wound healing. We propose that sirolimus should be used carefully (or even withheld) in patients with known or previous ulcer disease, and further that it should be used prudently and/or in conjunction with aggressive prophylaxis therapy in those at risk for ulcer disease.
Limitations of glomerular filtration rate equations in the renal transplant patient
Authors: Raju Dharmapaul L , Grover Vaneeta K , Shoker Ahmed
Published: March 2005

Abstract: This study aims to compare the performance of endogenous creatinine clearance (CLcr) and a number of published mathematical equations to calculate glomerular filtration rate (GFR) in renal transplant patients considering99mTc DTPA isotope scan as the reference method. A total of 152 GFR were performed on 81 renal transplant patients. Accuracy of each method was measured at different percentiles. The bias and precision of all the methods were then compared. A pairedt‐test was used to compare the performance of each calculation to the respective GFR measured by isotope study performed on the same day. In the total population, all calculated methods correlated significantly with the isotope results. Accuracies within specific ranges of the isotope GFR were limited in all equations (agreement with isotope result ≤72% at 30% accuracy range in the total group). Within the limited accuracy, Edwards’ equation (K.D. Edwards and H.M. Whyte,Australas Ann Med1959; vol. 8: p. 218) had the least bias in the total population. Bjornsson (T.D. Bjornsson,Clin Pharmacokinet1979; vol. 4: p. 200) had the least bias in patients with GFR ≥ 50 mL/min and Gates in patients with GFR < 50 mL/min. Salazar (D.E. Salazar and G.B. Corcoran,Am J Med1988; vol. 84: p. 1053) had the least bias in patients with BMI above 30 kg/m2and the Davis equation (G.A. Davis and M.H. Chandler,Am J Health Syst Pharm1996; vol. 53: p. 1028) in patients with BMI <25 kg/m2. In all analyses, Nankivell (B.J. Nankivell, S.M. Gruenwald, R.D.M. Allen and J.R. Chapman,Transplantation1995; vol. 59: p. 1683) overestimated GFR by more than 80% and MDRD 1 and 2 in <10% of the time. The results demonstrate the inherited limitation in the currently available equations to calculate GFR in renal transplant patients.
Cytomegalovirus prophylaxis with valganciclovir in African–American renal allograft recipients based on donor/recipient serostatus
Authors: Gruber Scott A , Garnick James , Morawski Katherina , Sillix Dale H , West Miguel S , Granger Darla K , El‐Amm Jose M , Alangaden George J , Chandrasekar Pranatharthi , Haririan Abdolreza
Published: March 2005

Abstract:  There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk‐stratified dosing regimen. Eighty adult African–American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 ± 8 months received VGC once daily for 90 d post‐transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R−) received 900 mg (n = 12); moderate risk (D+/R+, D−/R+) received 450 mg (n = 60); and low risk (D−/R−) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high‐risk (25%) and three in the moderate‐risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue‐invasive disease, resistance to treatment, or recurrence. D+/R− serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients.
Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre‐transplant diabetes
Authors: David Kristin M , Morris Jonathan A , Steffen Bettina J , Chi‐Burris Kathy S , Gotz Vincent P , Gordon Robert D
Published: March 2005

Abstract:  Outcomes specifically in mycophenolate mofetil (MMF)‐treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post‐transplant malignancies, and graft loss in MMF‐ or azathioprine (AZA)‐treated renal transplant patients with pre‐transplant diabetes. Outcomes were compared between MMF‐ (n = 14 144) and AZA‐ (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan–Meier survival analysis, Cox multivariable regression and chi‐square tests. MMF patients had less AR compared with AZA‐treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any‐cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies.
Arterial reconstruction with donor iliac vessels during pancreas transplantation: an intraoperative approach to arterial injury or inadequate flow
Authors: Moon Jang IL , Ciancio Gaetano , Burke George W
Published: March 2005

Abstract: Background: Outcome of pancreas transplantation (PTX) has improved because of use of novel immunosuppression and advances in surgical technique. It is not uncommon for severe atherosclerosis in patients with type 1 insulin‐dependent diabetes mellitus or the presence of a previously transplanted organ to limit the options for vascular anastomosis. Herein we report the novel application of donor iliac arterial interposition grafts for arterial reconstruction in patients with severe iliac artery arteriosclerosis, and/or previous transplant who develop an arterial injury or stenosis during surgery.

Methods: In five patients undergoing PTX, the external iliac artery was severely atherosclerotic and/or occupied by a previous vascular anastomosis. In four of the five patients, an arterial intimal dissection became apparent. The external iliac artery was excised and reconstructed with donor iliac artery interposition graft (end‐to‐end anastomosis). Pancreas or kidney was engrafted onto this arterial interposition graft (end‐to‐side anastomosis).

Results: There was no operative morbidity related to this surgical approach. All grafts functioned well after transplantation. Distal lower extremities have no evidence of vascular insufficiency with mean follow‐up of 26 months (7–45 months).

Conclusion: This surgical technique is an acceptable option during PTX for the patient with severe iliac artery arteriosclerosis with intraoperative intimal dissection or stenosis, or perhaps those with challenging arterial access.
Clinical utility of the Handicap Assessment and Resource Tool: An investigation of its use with the aged people in hospital
Authors: Barbara Anita , Whiteford Gail
Published: March 2005

Aims:  This article presents the findings of a qualitative study investigating the clinical utility of the Handicap Assessment and Resource Tool (HART). Clinicians’ perceptions of the HART were explored in its use in acute hospital settings in a regional health service in New South Wales, Australia.

Methods and Results:  The study, which used in‐depth, structured interviews with clinicians working in acute aged care, identified key themes, which point to an overall positive perception of the HART's clinical utility. The themes, identified through thematic analysis were: responses to structural features of the HART; processes of administration; perceived benefits for clients; and clinical utility in context. The article concludes with recommendations for the assessment of aged people in acute hospitals and the need for occupational therapists to continue analysing and establishing the clinical utility of the profession's assessment tools.

Conclusion:  The findings of the study support the clinical utility of the HART when used with aged people in acute care settings. Overall, though participants found it time consuming to administer, they judged the HART to be a context sensitive tool that addressed the complex needs of their patients.
Cell cycle regulation and its aberrations in human lung carcinoma
Authors: Dobashi Yoh
Published: March 2005

Cell cycle is strictly regulated by complex and redundant mechanisms. Basically, cell cycle transition is promoted by accelerator molecules termed ‘cyclin’ and ‘cyclin‐dependent kinase’ (cdk), and inhibited by brake molecules termed ‘cdk‐inhibitor’ (CKI). Although based on the results of early experimental studies and of clinicopathological analyses, there was much speculation that gene aberration of those molecules would be common; this has not turned out to be the case. One reason may be that activation or inactivation of a single molecule by itself usually does not lead to cell transformation, but rather to apoptosis. Successful transformation and unchecked cell proliferation appears to require the coordinated up‐regulation of cyclin/cdk and/or suppression of CKI. In this article, I focus on the precise regulation of the cell cycle and describe abnormalities found in these proteins in lung carcinoma. Notable findings in lung carcinoma include: (i) cyclin A/cdk2 plays a key role in cell proliferation, while protein amount of cyclin E does not necessarily reflect cellular proliferative activity, depending on the tumor type; (ii) CKI function not only as suppressors, but also as activators of cdk, depending on expression levels; and (iii) aberrant expression of cyclin/cdk can lead to apoptosis in vivo in humans. Another key point is that as lung carcinoma is composed of a mixture of heterogeneous histological subtypes, the growth control of carcinoma cells is diversely regulated, depending on each histological subtype. This diversity is also described with our experimental results.
Significant correlation of morphological remodeling in ulcerative colitis with disease duration and between elevated p53 and p21WAF1 expression in rectal mucosa and neoplastic development
Authors: Mitsuhashi Jun , Mikami Tetuo , Saigenji Katsunori , Okayasu Isao
Published: March 2005

Although a chronic inflammation‐carcinoma sequence has been proposed in cases of longstanding ulcerative colitis (UC), the relationship of morphological alteration or remodeling of regenerated mucosa to carcinoma development is yet to be clarified. Therefore, mucosae of 49 resected rectae from individuals with UC were histologically and quantitatively analyzed, with regard to thickness and morphological parameters of crypts, in relation to the disease duration, clinical disease activity and neoplastic development. An immunohistochemical examination of Ki‐67, p53, p21WAF1 and ssDNA labeling was also included. Significant correlations of number, height, angle, fusion and Paneth cell metaplasia of crypts, as well as thickness of the muscularis mucosae, were revealed with disease duration, as confirmed by three‐dimensional reconstructed image analysis. p53 and p21WAF1‐positive cells increased with disease duration and were significantly more frequent in cases with neoplasia, suggesting more DNA damage. However, this was not the case for ssDNA labeling, assessed as an indicator of apoptosis. In general, histological changes and p53, p21WAF1 and Ki‐67 labeling were correlated. In conclusion, histological parameters for mucosal remodeling correlate well with UC duration, indicating accumulation of structural alterations. Accumulated damage to DNA, reflected by increased p53 and p21WAF1 labeling indices, might be involved in cancer development, as well as longstanding inflammation.
PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors (GIST), especially useful for identifying KIT‐negative tumors
Authors: Motegi Atsushi , Sakurai Shinji , Nakayama Hiroko , Sano Takaaki , Oyama Tetsunari , Nakajima Takashi
Published: March 2005

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the digestive tract and the majority of GIST has characteristic gain‐of‐function mutations of the c‐kit gene, which encodes the KIT receptor for stem cell factor. The present study aimed to establish the usefulness of protein kinase C theta (PKC θ) as an immunohistochemical marker for GIST in comparison with KIT immunohistochemistry. PKC θ immunohistochemistry was carried out not only on 48 cases of GIST and another 40 cases of gastrointestinal mesenchymal tumors, but also on 24 cases of various tumors known to be immunohistochemically positive for KIT. Immunohistochemically, 41 out of 48 cases (85%) of GIST were positive for PKC θ, and its expression was confirmed by Western blot analysis using six cases of surgically resected GIST. In the present study there were six GIST immunohistochemically negative for KIT, which histologically revealed a myxoid epithelioid appearance characteristic to that of GIST with platelet‐derived growth factor receptor alpha mutation. All six GIST were immunohistochemically positive for PKC θ. No PKC θ immunoreactivity was observed in other gastrointestinal mesenchymal tumors and various KIT‐positive tumors except for three cases (14%) of gastrointestinal schwannomas. The present study revealed that PKC θ is an immunohistochemically novel and useful marker for GIST, especially for GIST negative for KIT.
Immunohistochemical analysis of cleaved caspase‐3 detects high level of apoptosis frequently in diffuse large B‐cell lymphomas of the central nervous system
Authors: Arai Momoko , Sasaki Atsushi , Saito Nobuhito , Nakazato Yoichi
Published: March 2005

The purpose of the present paper was to examine the level of apoptosis and the relationships among apoptosis, apoptosis‐associated proteins, and proliferating potential in lymphoma tissues to clarify the characteristics of apoptosis in diffuse large B‐cell lymphomas (DLBCL) of the central nervous system (CNS). The formalin‐fixed, paraffin‐embedded tissues of CNS and non‐CNS DLBCL (20 cases each) were studied by terminal deoxynucleotidyl transferase‐mediated dUTP‐nick end labeling (TUNEL) and immunohistochemistry, using antibodies against single‐stranded DNA (ssDNA), cleaved caspase‐3, bcl‐2, bax, p53, Fas and Ki‐67. The cleaved caspase‐3 immunohistochemistry detected apoptosis of the lymphoma cells most sensitively compared to TUNEL and ssDNA immunohistochemistry. High expression (grade + + or + + +) of cleaved caspase‐3 was found more frequently in CNS DLBCL (11 cases, 55%)  than non‐CNS DLBCL (three cases, 15%; P = 0.009). Bax‐positivity of lymphoma cells was increased in six cases of CNS DLBCL, which also showed high positivity of cleaved caspase‐3. There was no significant correlation between the cleaved caspase‐3‐positivity and the Ki‐67 positivity. The present study indicates that the number of apoptotic cells and expression level of cleaved caspase‐3 were significantly higher in CNS DLBCL than non‐CNS DLBCL, and that the correlation of bax and cleaved caspase‐3 expression was often present in CNS DLBCL.
Lung pathology of pale ear mouse (model of Hermansky–Pudlak syndrome 1) and beige mouse (model of Chediak–Higashi syndrome): Severity of giant lamellar body degeneration of type II pneumocytes correlates with interstitial inflammation
Authors: Tang Xiaoyan , Yamanaka Shoji , Miyagi Yohei , Nagashima Yoji , Nakatani Yukio
Published: March 2005

The authors have recently reported the presence of characteristic foamy swelling/degeneration (giant lamellar body degeneration, GLBD) of type II pneumocytes in the lungs affected by Hermansky–Pudlak syndrome (HPS)‐associated interstitial pneumonia (HPSIP), and proposed the hypothesis that GLBD may be the triggering factor in the development of HPSIP (Virchows Arch 2000; 437: 304–13). The purpose of the present paper was to investigate the lung pathology of pale ear (ep) mouse, a mouse model of HPS1, and of beige (bg) mouse, a mouse model of Chediak–Higashi syndrome (CHS) with a reference to GLBD and associated pathologic changes. GLBD was found in both ep and bg mice soon after birth, and increased in severity as the mice grew older. Younger mice had only GLBD with no evidence of interstitial change. Aged bg mice showed the most prominent GLBD and patchy areas of alveolar collapse accompanied by lymphocytic infiltration and slight fibrosis. Aged ep mice with less severe GLBD than bg mice of comparable ages also had a slight tendency to develop interstitial inflammation but no fibrosis. The pneumocytes with GLBD were immunoreactive for surfactant protein B and composed of giant lamellar bodies ultrastructurally, findings which were almost identical to those of human GLBD. The results of the present study support the hypothesis that GLBD may play an important role in the development of HPSIP. Ep and bg mice, especially the latter, may be useful mouse models of HPSIP.
Using recombinant human thyroid‐stimulating hormone for the diagnosis of recurrent thyroid cancer
Authors: Blamey Stephen , Barraclough Bruce , Delbridge Leigh , Mernagh Paul , Standfield Lachlan , Weston Adele
Published: March 2005

Background:  Recombinant human thyroid‐stimulating hormone (rhTSH) has been suggested as a diagnostic agent in the diagnosis of recurrent thyroid cancer, instead of the current practice of thyroid hormone (THT) withdrawal.

Methods:  An evidenced‐based literature review was used as the basis for a cost‐utility, decision‐analytic model. Outcome measures were safety, efficacy (diagnostic performance and quality of life) and cost effectiveness of rhTSH.

Results:  The literature search identified six comparative studies of rhTSH versus THT withdrawal. The most common adverse events associated with the use of rhTSH were headache (3.5−11.1%) and nausea (7.7−17%). When used as a diagnostic agent, the unadjusted sensitivity and specificity for rhTSH were 87% and 95%, respectively. Thus the use of rhTSH instead of THT withdrawal would result in a reduction in diagnostic accuracy, with 11% of patients’ disease status being misclassified. Use of rhTSH resulted in a higher quality of life in the period prior to diagnostic testing than THT withdrawal (P < 0.001). When the impact of diagnostic performance, patient compliance to follow‐up and modified quality of life were modelled over a 5 year time‐frame, the incremental cost per QALY of rhTSH relative to THT withdrawal was $51 344.42.

Conclusions:  The use of rhTSH as a diagnostic agent appears to be safe but less diagnostically accurate and less cost‐effective (on whole of healthcare cost basis) when used in the follow‐up of patients with thyroid cancer who have had a previous negative radioiodine scan after thyroid hormone withdrawal.
Cost‐effective method for laparoscopic choledochotomy
Authors: Griniatsos John , Karvounis Evangelos , Arbuckle James , Isla Alberto‐Martinez
Published: March 2005

Background:  Recent reports have noted that postoperative complications following open or laparoscopic choledochotomy for common bile duct (CBD) exploration are mainly related to the T‐tube presence, and that there has been no trend of decrease in the laparoscopic era. Laparoscopic endobiliary stent placement with primary closure of the CBD has been proposed as a safe and effective alternative to T‐tube placement.

Methods:  Between January 1999 and January 2003, 53 consecutive patients suffering from proven choledocholithiasis underwent laparoscopic common bile exploration (LCBDE) via choledochotomy. In the early period, a T‐tube was placed at the end of the procedure (group A, n = 32) while, from June 2001 onwards, laparoscopic biliary stent placement and primary CBD closure were chosen as the drainage method (group B, n = 21).

Results:  Six patients developed T‐tube‐related complications postoperatively. Univariate analysis revealed statistically significant lower morbidity rate and shorter postoperative hospital stay for the stent group. Although not statistically significant, a median saving of £780 per patient was observed in the stent group.

Conclusion:  Biliary endoprosthesis placement following laparoscopic choledochotomy avoids the well‐known complications of a T‐tube, leading to a shorter postoperative hospital stay. The method is safe and effective and it should also be considered as cost‐effective compared to T‐tube placement. Further studies are required in order to document cost‐effectiveness of the method.
Effect of dexamethazone on hepatic vascular response in experimental sepsis
Authors: Tarim Mehmet Akin , Sayek Iskender , Erdemli Inci
Published: March 2005

Background:  The aim of the present study was to evaluate the effect of dexamethasone‐pretreatment on the hepatic artery and portal vein of septic rats, which were generated by lipopolisaccarides (LPS) intraperitoneal injection.

Method:  Thirty‐six albino Wistar rats were used and constructed as LPS (n = 12), control (n = 12), dexamethazone‐pretreatment (n = 6) and dexamethazone‐control (n = 6) groups. Hepatic artery and portal vein rings were excised and placed in Krebs−Henseleit solution. Vessel rings were contracted with phenylephrine adding to the organ chamber in cumulative doses. Then the contraction‐response curves were drawn.

Results:  In the LPS group, phenylephrine evoked contractions were reduced in both hepatic artery and portal vein rings in comparison to the control group. In the dexamethasone‐control group, phenylephrine‐evoked contractions were increased but not significantly. Dexamethasone‐pretreatment increased the phenylephrine‐evoked contractions close to the values of control group for both types of rings.

Conclusions:  Dexamethasone pretreatment corrected the vascular hyporeactivity to phenyleprine in isolated portal vein and hepatic artery rings prepared from the LPS treated rats in experimental sepsis. This might have occurred as a result of inhibition of inducible nitric oxide synthase expression.