bluuebunny/crossref_metadata_2025 huggingface dataset:
Les pronoms clitiques sujets en picard: une analyse au confluent de la phonologie, de la morphologie et de la syntaxe
Authors: AUGER JULIE
Published: June 2003

Cet article examine les clitiques sujets du picard. Comme le français familier, le picard ‘redouble’ les sujets lexicaux à l'aide d'une copie pronominale, ce qui soulève la possibilité que les pronoms sujets soient devenus des marques affixales d'accord verbal. Les tests morphophonologiques et morphosyntaxiques auxquels nous soumettons les clitiques sujets révèlent que s'ils sont devenus de véritables marques d'accord, leur comportement n'est pas tout à fait celui d'affixes lexicaux. Nous proposons donc qu'ils sont générés sous Agr dans la structure syntaxique et qu'ils se cliticisent au verbe en forme phonologique pour former un Groupe Clitique tel que proposé par Hayes 1989.
Lipids during Bufo arenarum oogenesis
Authors: Bruzzone Ariana , Buschiazzo Jorgelina , Alonso Telma S.
Published: June 2003

The content and composition of phospholipids and triacylglycerols (TAGs) in Bufo arenarum oocytes in stages III and IV of their oogenesis were studied. The total amount of phospholipids in stage IV oocytes is 0.5-fold higher than in stage III oocytes. In both cases, the main phospholipids are phosphatidylcholine (PC) and phosphatidylethanolamine (PE). A striking observation concerns the high level of diphosphatidylglycerol (DPG) in stage III oocytes, which could be indicative of a relatively larger mitochondrial population with respect to other oogenetic stages. A net increase in sphingomyelin content was found during oogenesis. This fact could be related to the role of this phospholipid in the signal transductional pathways. In PC, palmitic (16:0), linoleic (18:2) and oleic (18:1) are the major fatty acids for both types of oocytes, while in PE the main acyl groups are 18:1, 16:0, arachidonic acid (20:4n6) and 18:2. PE is more unsaturated than PC and both phospholipids are more unsaturated in stage III oocytes than in stage IV oocytes. The amount of triacylglycerols is 0.3-fold higher in stage IV oocytes than in stage III oocytes. In both stages, the main fatty acids are 18:2, 18:1 and 16:0. During oogenesis, a significant increase in 18:1 and 18:3n3, and a decrease in 18:2 of TAG were found. The unsaturation index of TAGs from stage IV oocytes is higher than that from stage III oocytes. The TAG increase during oogenesis is consistent with the putative use of these lipids as a source of energy in embryo development.
Effect of prooxidant agents added at the morula/blastocyst stage on bovine embryo development, cell death and glutathione content
Authors: Feugang Jean-Magloire , Van Langendonckt Anne , Sayoud Hichem , Rees Jean-François , Pampfer Serge , Moens André , Dessy Franz , Donnay Isabelle
Published: June 2003

Two prooxidant agents, 2,2′-azobis(2-amidinopropane)dihydrochloride (AAPH), a generator of free radicals in the culture medium, and buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, were used to reinforce from the morula stage (day 5 post-insemination, p.i.) the oxidative stress encountered by bovine embryos in culture. Exposure to increasing concentrations of both prooxidants from the morula stage did not affect blastocyst formation but some blastocysts were found degenerated on day 8 in a dose-dependent manner (0, 0.001, 0.01, 0.1 mM AAPH gave respectively 0, 10%, 32%, 48% degeneration, while 0, 0.1, 0.2, 0.4 mM BSO led respectively to 0, 14%, 30%, 41% degeneration). Hatching rates and cell numbers of surviving blastocysts were not affected. Morulae and early blastocysts exposed from day 5 to day 6 p.i. appeared more resistant than expanded blastocysts (75-80% survival vs 20-65%; p <0.05). Treatment with BSO significantly decreased the level of reduced glutathione in day 7 blastocysts (0.02 vs 0.42 pmol per embryo in the control) while AAPH had no effect (0.38 pmol per embryo). The proportion of cells showing membrane lesions was increased in degenerated blastocysts from day 7.5 p.i. In AAPH-treated, but not in BSO-treated embryos, cell membrane permeabilisation seems to occur before blastocyst degeneration. DNA fragmentation evaluated by the TUNEL technique was increased in day 7 blastocysts by both prooxidants (2.8 ± 0.4 in the control group vs 4.5 ± 0.4 and 6.0 ± 0.4 respectively in the AAPH- and BSO-treated groups). Addition of an inhibitor of caspase-3, DEVD-CHO, partially prevented DNA fragmentation, indicating that prooxidant treatment induced a caspase-dependent pathway of apoptosis.
Reversible changes in protein phosphorylation during germinal vesicle breakdown and pronuclear formation in bovine oocytes in vitro
Authors: Chian R.C. , Chung J.T. , Niwa K. , Sirard M.A. , Downey B.R. , Tan S.L.
Published: June 2003

This study examined the event of protein phosphorylation in bovine oocytes during germinal vesicle breakdown (GVBD) and formation of pronuclei following fertilisation in vitro. Immature oocytes were obtained from abattoir materials and cultured in vitro. The oocytes were labelled with [32P]orthophosphate at 3 h intervals from 0 to 12 h following maturation in culture or from 3 to 18 h following insemination. One-dimensional gel electrophoresis indicated that levels of protein phosphorylation are low prior to GVBD. However, the levels of protein phosphorylation at approximately 40 kDa, 27 kDa, 23 kDa and 18 kDa increased substantially following GVBD and then decreased gradually as maturation in culture progressed. In contrast, the levels of protein phosphorylation increased gradually in the oocytes following pronucleus formation. Further, two-dimensional gel electrophoresis indicated that the protein at approximately 18 kDa reversibly changed in the oocytes during maturation and fertilisation. These results indicate that the reversible changes of this phosphoprotein may be related to either cell cycle transition or pronucleus formation during maturation and fertilisation in bovine oocytes.
Oocyte age and nuclear donor cell type affect the technical efficiency of somatic cloning in rabbits
Authors: Cervera Rita P. , García-Ximénez Fernando
Published: June 2003

The present study in rabbits compared, in the first experiment, the effect of two commonly used oocyte ages, 13 h and 17 h after ovulation induction treatment, on the technical efficiency of somatic nuclear transfer steps, using fresh cumulus cells as nuclear donors. Recently ovulated metaphase II oocytes (13 h) showed higher fusion (13 h: 83% vs 17 h: 67%, p < 0.05) and in vitro development rates than in vivo slightly aged metaphase II oocytes (morula, 13 h: 74% vs 17 h: 25%, p < 0.05; blastocyst, 13 h: 16% vs 17 h: 8%; p < 0.05). In contrast, activation rate was higher in the 17 h group (13 h: 45% vs 17 h: 67%; p < 0.05). In a second experiment, using recently ovulated oocytes (13 h) as recipients, two donor cell types (from primary cultures of either cumulus cells or fetal fibroblasts) were tested to evaluate their effects on the efficiencies of the different technical steps of somatic nuclear transfer procedure. A better fusion rate was obtained when fetal fibroblasts were used as nuclear donors (cumulus cells: 45% vs fetal fibroblasts: 67%, p < 0.05). No statistically significant differences were detected in cleavage rate regardless of the cell type used (cumulus cells: 44% vs fetal fibroblasts: 60%, p > 0.05). However, in vitro development to morula (cumulus cells: 41% vs fetal fibroblasts: 14%, p < 0.05) and to blastocyst stage (cumulus cells: 27% vs fetal fibroblasts: 3%, p < 0.05) were different between cell types.
Application of finite-state transducers to the acquisition of verb subcategorization information
Authors: ALDEZABAL I. , ARANZABE M. , GOJENOLA K. , ORONOZ M. , SARASOLA K. , ATUTXA A.
Published: June 2003

This paper presents the design and implementation of a finite-state syntactic grammar of Basque that has been used with the objective of extracting information about verb subcategorization instances from newspaper texts. After a partial parser has built basic syntactic units such as noun phrases, prepositional phrases, and sentential complements, a finite-state parser performs syntactic disambiguation, determination of clause boundaries and filtering of the results, in order to obtain a verb occurrence together with its associated syntactic components, either complements or adjuncts. The set of occurrences for each verb is then filtered by statistical measures that distinguish arguments from adjuncts.
Finite state methods in natural language processing
Authors: KARTTUNEN LAURI , KOSKENNIEMI KIMMO , VAN NOORD GERTJAN
Published: June 2003

Finite state methods have been in common use in various areas of natural language processing (NLP) for many years. A series of specialized workshops in this area illustrates this. In 1996, András Kornai organized a very successful workshop entitled Extended Finite State Models of Language. One of the results of that workshop was a special issue of Natural Language Engineering (Volume 2, Number 4). In 1998, Kemal Oflazer organized a workshop called Finite State Methods in Natural Language Processing. A selection of submissions for this workshop were later included in a special issue of Computational Linguistics (Volume 26, Number 1). Inspired by these events, Lauri Karttunen, Kimmo Koskenniemi and Gertjan van Noord took the initiative for a workshop on finite state methods in NLP in Helsinki, as part of the European Summer School in Language, Logic and Information. As a related special event, the 20th anniversary of two-level morphology was celebrated. The appreciation of these events led us to believe that once again it should be possible, with some additional submissions, to compose an interesting special issue of this journal.
Review Essay: Recent Trends in Comparative Political Economy and their Implications for Japan
Authors: NOBLE GREGORY W.
Published: June 2003

Books reviewed

Peter A. Hall and David Soskice (eds.), Varieties of Capitalism: The Institutional Foundations of Comparative Advantage, New York: Oxford University Press, 2001.

J. Rogers Hollingsworth and Robert Boyer (eds.), Contemporary Capitalism: The Embeddedness of Institutions, Cambridge: Cambridge University Press, 1997.

Torben Iversen, Contested Economic Institutions: The Politics of Macroeconomics and Wage Bargaining in Advanced Democracies, Cambridge: Cambridge University Press, 1999.

Torben Iversen, Jonas Pontusson and David Soskice (eds.), Unions, Employers, and Central Banks: Macroeconomic Coordination and Institutional Change in Social Market Economies, Cambridge: Cambridge University Press, 2000.
Gender and Voting Preferences in Japanese Lower House Elections
Authors: STEEL GILL
Published: June 2003

This paper analyzes voter choice in selected House of Representatives elections during the past 30 years. I estimate multinomial probit models using data from the Akarui Senkyo Suishin Kyokai (Society for the Promotion of Clean Elections) surveys and use qualitative data gathered in focus groups. I argue that no gender gap exists in the votes garnered by the main parties because, first, influential people are not simply able to ‘deliver’ votes from their networks — most accounts of voter choice fail to discuss gender, an oversight considering that most networks are gender-based — and, second, ‘women's issues’ have no special relevance to women in their vote choice. Instead, women and men vote for the Liberal Democratic Party because they associate the Party with stability and increased standards of living, including substantial social provisions.
Exploring the North–South Gap Longitudinally
Authors: REUVENY RAFAEL , THOMPSON WILLIAM R.
Published: June 2003

Previous studies on economic convergence have been handicapped by the lack of sufficient serial data. Real GDP per capita are now available for 56 states. With some interpolation, we create series from 1870 to 1992 for Northern (developed countries) and Southern (lesser developed countries) aggregates. The data are explored by extending the leadership-long cycle perspective to deal with convergence. We find that North–South inequalities, at least those based on GDP per capita data, have been expanding. The corresponding growth rates reveal long waves, providing an important clue related to iterations of radical technological changes and their incomplete diffusion in explaining the North–South gap. We believe that convergence is unlikely any time soon without radical restructuring of global economic growth prospects.
What Mechanism Causes the M + 1 Rule? A Simple Simulation
Authors: REED STEVEN R.
Published: June 2003

The M + 1 Rule, that at equilibrium there should be only one more candidate running than seats available, extended Duverger's Law to the cases of more than one seat per district. Both the M + 1 rule and Duverger's Law have been confirmed repeatedly, albeit always with qualification. Yet we have reached no consensus on the mechanism that produces these two empirical regularities. In this paper I use a simple simulation to test the hypothesis that the mechanism is that candidates retire after some fixed number of consecutive losses. I test the results of the simulation against several different empirical results and find a reasonably good fit. I also add a mechanism for increasing the number of candidates. These results suggest that the M + 1 rule and Duverger's law may be the result not of rational calculation but of some simple set of decision rules. The analysis also illustrates the usefulness of a simulation approach to hypothesis testing.
The Agent-Structure Co-Constitution and the Vietnam Commitment Decisions: A Rejoinder to Yuen Foong Khong
Authors: DUFFY GAVAN
Published: June 2003

This essay responds to Yuen Foong Khong's (2002) spirited defence of his Analogies at War: Korea, Munich, Dien Bien Phu, and the Vietnam Decisions of 1965 (Khong, 1992). The author had earlier criticized Khong's overemphasis of agency over structure in his accounting of the 1965 US troop deployment decisions (Duffy, 2001). This essay points to several deficiencies in Khong's defence. Chief among them are (a) the inconsistency between Khong's conception of structure and his professed constructivism, and (b) the false dualism between agency and structure open which Khong's defence rests.
Psychometric Properties of a Spanish Adaptation of the Matching Familiar Figures Test (MFFT-20)
Authors: Buela-Casal G. , Carretero-Dios H. , De los Santos-Roig M. , Bermúdez M.P.
Published: June 2003

Summary: This study constitutes the first stage of the Spanish adaptation of the Matching Familiar Figures Test 20 (MFFT-20; Cairns & Cammock, 1978 ). The normative data for reflexivity-impulsivity and efficiency-inefficiency were obtained by means of the Salkind and Wright formula (1977) . The study sample was composed of 700 Spanish children, aged 6 to 12. This paper presents the results for reliability and latency-error correlation. The development of errors and latencies at older ages and gender differences were also analyzed. No significant differences between boys and girls were observed with respect to any of the variables. A high reliability was established for errors as well as for latencies. Errors decreased and latency increased with age. It is important to note that the data for both sexes at 8, 9, and 10 years of age reveal a stabilization in the latencies even though the errors continue to decrease. The psychometric properties of the Spanish adaptation of the MFFT-20 are discussed. Results are analyzed by examining the instrument's validation using the normative data presented here. The study concludes that the MFFT-20 is a reliable and valid measure of reflexivity-impulsivity.
Morphological and biochemical effects of immunosuppressive drugs in a capillary tube assay for endothelial dysfunction
Authors: Wilasrusmee Chumpon , Da Silva Monica , Singh Bhupinder , Siddiqui Josephine , Bruch David , Kittur Smita , Wilasrusmee Skuntala , Kittur Dilip S
Published: June 2003

Abstract: Immunosuppressive drugs common in clinical transplantation are known to have untoward effects on the vascular system. The effects of some drugs, notably cyclosporin A (CyA), have been studied on the vascular system, while those of others have not. In the vascular system, endothelial cells are the predominant cell type exposed to intravascular concentrations of immunosuppressive drugs. We therefore studied the effects of drugs common in clinical transplantation on endothelial cells in a capillary tube assay. The endothelial cells in the capillary tubes are morphologically more similar to those in the microvasculature than endothelial cells in monolayers. We studied the kinetics and extent of capillary tube formation and prostacyclin (PGI2) and endothelin‐1 (ET‐1) release from the in vitro capillaries to determine the morphological and biochemical effects of five immunosuppressive agents on endothelial function. We found a significant difference in the morphological and biochemical effects of the two common calcineurin inhibitors, CyA and tacrolimus (FK506) on capillary morphology in vitro. The former had a pronounced injurious effect on the morphology of the in vitro capillaries, while the latter did not. CyA also significantly increased ET‐1 release by the capillaries, but FK506 did not. Mycophenolate mofetil (MMF) was the only other agent that had a moderately injurious effect on the morphology of the in vitro capillaries. Sirolimus (rapamycin) and dexamethasone, similar to FK506, had no effect on the capillary morphology. All these agents, except dexamethasone, increased PGI2 release. Our data suggest that CyA adversely affects the morphology of the microvasculature and that this is mediated, at least partly, by an increased ET‐1 release by endothelial cells exposed to CyA. These findings describe a novel effect of CyA and MMF on endothelial cells that could be relevant to understanding the mechanisms of immunosuppressive drug‐mediated endothelial injury in clinical transplantation.
Histopathological study of renal transplant artery stenosis: role of rejection and cold ischaemia time in the pathogenesis of intimal hyperplasia in an arterial allograft
Authors: Xenos Eleftherios S , Pacanowski John P , Ragsdale John , Kirkpatrick Stacy , Stevens Scott L , Freeman Michael B , Goldman Mitchell H
Published: June 2003

Abstract:  Introduction:  Intimal hyperplasia of renal allograft arteries is a cause of hypertension and graft loss and the predisposing factors are poorly understood. We performed a histopathological study focusing on cold ischaemia time and immunological factors and their effect on the donor artery.

Methods: Primary renal artery branches were obtained from patients undergoing transplant nephrectomy for chronic rejection. Non‐transplant patients undergoing nephrectomy served as controls. Clinical information including immunosuppression and rejection episodes, cold ischaemia time and graft survival were collected from the patients' charts. Collagen, smooth muscle cells, T cells, macrophages, and neutrophils were quantified using immunohistochemistry. The intima to media ratio was also calculated using imaging software. Statistical analysis was performed using linear regression and the Mann–Whitney test with P < 0.05 significant.

Results: Nine transplant patients and five controls were included. All transplant patients received maximum immunosuppression according to clinical standards. The median number of acute rejection episodes was 1 (range 0–5). Cold ischaemia time was 24.3 ± 9.6 h (mean ± SD). Mean allograft longeviy was 87.4 ± 72.9 months (mean ± SD). The intima/media ratio in the transplant group was higher as compared with the control (P = 0.002). The same was true for intima collagen content (P = 0.001) and intima smooth muscle content (P = 0.036). Cold ischaemia time was 19.6 ± 11.1 h (mean ± SD) and did not correlate with intima/media ratio. Also the number of rejection episodes did not correlate with the intima/media ratio.

Conclusion: Intimal hyperplasia in the allograft artery has a multifactorial aetiology. We were not able to establish an association between intimal hyperplasia and acute rejection episodes or length of cold ischaemia time. It appears that immunosuppression does not prevent the development of intimal hyperplasia.
A pilot protocol of a calcineurin‐inhibitor free regimen for kidney transplant recipients of marginal donor kidneys or with delayed graft function
Authors: Shaffer David , Langone Anthony , Nylander William A , Goral Simin , Kizilisik A Tarik , Helderman J Harold
Published: June 2003

Abstract: Background: The worsening shortage of cadaver donor kidneys has prompted use of expanded or marginal donor kidneys (MDK), i.e. older age or donor history of hypertension or diabetes. MDK may be especially susceptible to calcineurin‐inhibitor (CI) mediated vasoconstriction and nephrotoxicity. Similarly, early use of CI in patients with delayed graft function may prolong ischaemic injury. We developed a CI‐free protocol of antibody induction, sirolimus, mycophenolate mofetil, and prednisone in recipients with MDK or DGF.

Methods: Adult renal transplant recipients who received MDK or had DGF were treated with a CI‐free protocol consisting of antibody induction (basiliximab or thymoglobulin), sirolimus, mycophenolate mofetil, and prednisone. Serial biopsies were performed for persistent DGF. Patients were followed prospectively with the primary endpoints being patient and graft survival, biopsy‐proven acute rejection, and sirolimus‐related toxicity.

Results: Nineteen recipients were treated. Mean follow‐up was 294 days. Actuarial 6‐ and 12‐month patient survival was 100% and 100% and graft survival was 93% and 93%, respectively. The only graft loss was due to primary non‐function (PNF). The incidence of AR was 16%. Mean serum creatinine at last follow‐up was 1.6 mg/dL. Sirolimus‐related toxicity included lymphocele (1), wound infection (2), thrombocytopenia (1) and interstitial pneumonitis (1).

Conclusion: A CI‐free protocol with antibody induction and sirolimus results in low rates of AR and PNF and excellent early patient and graft survival in patients with MDK and DGF. CI‐free protocols may allow expansion of the kidney donor pool by encouraging utilization of MDK at high risk for DGF or CI‐mediated nephrotoxicity.
Delayed graft function may not adversely affect short‐term renal allograft outcome
Authors: Browne Barry J , Holt Cynthia Op't , Emovon Osemwegie E
Published: June 2003

Abstract:Introduction:Delayed graft function (DGF) is commonly believed to adversely impact both short‐ and long‐term renal allograft function. Because immunosuppressive therapy is commonly altered after DGF is identified, retrospective analyses are difficult to interpret. We therefore prospectively sought to examine the natural history of DGF in a controlled patient population under identical immunosuppressive protocols.

Methods:Adult patients undergoing cadaveric renal transplantation were treated with sequential triple drug immunotherapy. High‐dose steroids were administered in the operating room and rapidly tapered to 20 mg prednisone by post‐operative day (POD) 6. Cyclosporine (CsA) microemulsion was begun on POD 1, and dosed asymmetrically at 12‐h intervals to reach a daytime Cav of 650 ng/mL (utilizing 2‐h and 6‐h levels), while PM doses were adjusted to an AM trough of 300 ng/mL. Mycophenolate (1000 mg q12 h) was added on POD 3 in most patients and discontinued after 3 months. No induction agents were used. All patients were followed for at least 6 months.

Results:Sixty consecutive patients received 64 allografts (four double grafts). In all, 17 patients required dialysis and were considered to have DGF. Eight of these patients received marginal organs turned down by at least one other centre. Cold ischaemia time was significantly longer in patients with DGF (24 h vs. 19 h,P < 0.01) All patients were treated as planned and there were no major protocol violations. One patient had primary non‐function and was excluded from analysis. CsA trough and Cav values were similar between groups. Mean serum creatinine levels (mg/mL) fell more slowly in patients with DGF but there was no significant difference by 3 months (1.7 vs. 1.5) and the creatinine clearance was not significantly different between the groups after 1 year (71 cm3/min in DGF vs. 61 cm3/min,P = 0.13). Our data demonstrate that alterations in routine immunosuppressive strategies may not be necessary to achieve equivalent outcomes in patients with DGF.
Laparoscopic procurement model for living donor liver transplantation
Authors: Pinto Peter A , Montgomery Robert A , Ryan Bradley , Roberts William , Hsu Thomas , Kavoussi Parviz , Klein Andrew S , Kavoussi Louis R , Molmenti Ernesto P
Published: June 2003

Abstract:  Background/Aims:  Noting the contribution to renal transplantation by the introduction of the laparoscopic approach to donor nephrectomy, we investigated the possibility of performing a laparoscopic hepatic lobe procurement with the goal of performing a live donor liver transplantation. We describe our technique and determine its feasibility for such a goal.

Methods:  The surgical technique was developed over a series of 12 adult female pigs and adapted in two human cadavers. The technique included pneumoperitoneum with CO2, mobilization of the liver, and transection of the parenchyma into right and left lobes with a laparoscopic cavitron ultrasonic aspirator. The vascular inflow and outflow structures (hepatic artery, portal vein, hepatic veins) of the anatomical specimen being procured were preserved undisturbed during the hepatic transection. No temporary vascular occlusion techniques were utilized. The vascular structures were stapled and sectioned just prior to removal of the specimen.

Results:  Hepatic lobectomies were successfully performed laparoscopically. Vascular and biliary structures were preserved to allow for subsequent transplantation. Operative time from establishment of pneumoperitoneum to lobe procurement was under 4 h.

Conclusions:  This study demonstrates the feasibility of laparoscopic living donor procurement for liver transplantation, from both a technical and a physiological perspective.
Recipient outcome following living donor kidney transplantation using kidneys procured laparoscopically
Authors: Reddy K Sudhakar , Mastrangelo Michael , D Johnston Thomas , Khan Taqi , Waid Thomas , McKeown Wade , Lucas Bruce , Ranjan Dinesh
Published: June 2003

Abstract:  Background:  Laparoscopic live donor nephrectomy is becoming increasingly popular as it has been shown to minimize donor morbidity, length of hospital stay and length of time to return to work. Initial experience suggested that kidneys procured laparoscopically had higher rates of delayed graft function and ureteric complications but with increasing experience, these complications have become less common.

Methods: Retrospective chart review of all patients who underwent living donor kidney transplant using kidneys procured laparoscopically at our centre was performed. From the initiation of the laparoscopic donor nephrectomy programme at our institution in November 1998 until February 2002, we performed 71 living donor kidney transplants (69 kidneys procured laparoscopically and two procured by open donor nephrectomy after failed laparoscopic approach). Donor left kidney was used in all except in one patient. Mean duration of warm ischaemia time was 206 ± 79 s.

Results: The mean age of the recipients was 42 ± 15 years (range 1–68) including five paediatric recipients (age < 18 years). There were 48 males and 23 females. Nine (13%) were retransplants (seven second transplants and one each of third and fourth transplants). Two patients died with functioning grafts and four patients lost the graft (three thrombosis, one anastomotic rupture). No patient developed ureteric complications. The incidence of delayed graft function (need for dialysis in the first week post‐transplant) was 4%. Patient and graft survival rates (actual) were 97% and 91%, respectively. Mean length of hospital stay was 9 ± 7 days (median 7 days).

Conclusions: Recipient outcome is not compromised and excellent results can be achieved with living donor kidney transplantation using laparoscopically procured kidneys.
Point‐of‐care testing in an organ procurement organization donor management setting
Authors: Baier K A , Markham L E , Flaigle S P , Nelson P W , Shield C F , Muruve N A , Aeder M I , Murillo D , Bryan C F
Published: June 2003

Abstract: Purpose:  Our organ procurement organization (OPO) evaluated the clinical and financial efficacy of point‐of‐care testing (POCT) in management of our deceased organ donors.

Methods: Before we implemented point‐of care testing with the i‐STAT into routine clinical donor management, we compared the i‐STAT result with the result from the respective donor hospital lab (DHL) for certain analytes on 15 consecutive donors in our OPO from 26 March to 14 May 2001. The financial impact was studied by reviewing 77 donors from July 2001 to March 2002.

Results: There was a strong correlation for each analyte between the POC and DHL test results with r‐values as follows: pH 0.86; PCO2 = 0.96; PO2 = 0.98; sodium = 0.98; potassium = 0.95; chloride = 0.94; BUN = 0.98; glucose = 0.92; haematocrit = 0.87 and creatinine = 0.95. Since our OPO coordinators began using i‐STAT in their routine clinical management of organ donors, they can now more quickly maximize oxygenation and fluid management of the donor and make extra‐renal placement calls sooner. Finally, since we are no longer being billed for the testing performed on the i‐STAT, average financial savings to our OPO are $733 per case.

Conclusions: Point‐of‐care testing in management of our OPO donors provides a result that is equivalent to that of the donor hospital lab, has quicker turn‐around time than the donor hospital laboratory, allowing more immediate clinical management decisions to be made so that extra‐renal offers may begin sooner.
Maintenance triple immunosuppression with cyclosporin A, mycophenolate sodium and steroids allows prolonged survival of primate recipients of hDAF porcine renal xenografts
Authors: Cozzi Emanuele , Vial Conrad , Ostlie Daniel , Farah Bhatti , Chavez Gilda , Smith Kenneth G. C. , Bradley John R. , Thiru Sathia , . Davies Hugh F. S , Wallwork John , White David J. G. , Goddard Martin , Friend Peter J.
Published: June 2003

Abstract:  To date, the best results in life‐supporting pig‐to‐primate renal xenotransplantation have been obtained in recipients exposed to long‐term immunosuppression with cyclophosphamide. As this agent is frequently associated with side‐effects, we have explored the potential of a mycophenolate sodium‐based maintenance immunosuppression in this model. Human decay‐accelerating factor (hDAF) transgenic kidneys were transplanted into splenectomized and bilaterally nephrectomized cynomolgus monkeys immunosuppressed with mycophenolate sodium, cyclosporin A and steroids, and exposed to a brief induction course with cyclophosphamide (up to four doses). After transplantation, the primates were monitored daily for biochemical and haematological evaluations and for the measurements of haemolytic anti‐pig antibodies (APA). A detailed histological analysis of each explanted graft was also performed. All the animals showed very poor initial graft function but survived for up to 51 days. In contrast to our previous studies in xenograft recipients on long‐term immunosuppression with cyclophosphamide, minimal or no circulating xeno‐directed antibodies, as measured by the evaluation of APA titres, were detected in this series although some degree of acute humoral rejection was observed in all the explanted grafts and was the primary cause of graft failure. Furthermore, in addition to areas of humorally mediated graft damage, we have observed for the first time areas with exclusive and prominent infiltration by CD2+ and CD8+ mononuclear cells presenting patterns compatible with tubulitis, glomerulitis and arteritis, which we have called acute cellular xenograft rejection (ACXR). In addition, CD68+ infiltrating macrophages and CD20+ B‐cells were also present. This study demonstrates that a triple maintenance immunosuppression with mycophenolate sodium, cyclosporin A and steroids is a viable alternative to a cyclophosphamide‐based immunosuppression to obtain prolonged survival of porcine organs transplanted into primates. However, a more stringent control of antibody forming cells remains essential to further extend the survival of xenografts in this model. In addition, the use of the immunosuppressive regimen reported here in the primate is associated with the occurrence of a new category of cell‐mediated xenograft injury (ACXR) whose significance has yet to be clarified.
Ajoene inhibits the activation of human endothelial cells induced by porcine cells: implications for xenotransplantation
Authors: Benatuil Lorenzo , Apitz‐Castro Rafael , Romano Egidio
Published: June 2003

Abstract: Ajoene, is an organosulfur compound derived from garlic that strongly inhibit platelet aggregation, proliferation of human lymphocytes induced by phytohemagglutinin, and in general, blocks membrane‐mediated signaling of cell activation. As a thrombotic microangiopathy frequently complicates procedures designed to induce pig‐to‐baboon chimerism by infusion of large amounts of pig progenitor cells in baboons, it was thought that ajoene might be useful to prevent such complication. For such purpose, we studied the effects of ajoene on the activation of human umbilical vein endothelial cells (HUVEC) induced by pig peripheral blood mononuclear cells (p‐PBMC). Co‐cultures of p‐PBMC with HUVEC results in activation of the HUVEC as shown by over‐expression of E‐selectin and vascular cells adhesion molecule‐1 (VCAM‐1). Ajoene (25 μm) strongly inhibits HUVEC activation induced by tumor necrosis factor‐α (TNF‐α) or p‐PBMC as shown by a down regulation of VCAM‐1 and of E‐selectin expression. After 5 or 8 h of pre‐treatment with Ajoene, HUVEC incubated with TNF and p‐PBMC showed an E‐selectin or VCAM‐1 expression, respectively, at levels similar to the positive control indicating that the inhibitory effect is transient. Ajoene at concentration of 25 μm or lower did not affect HUVEC viability. Based on the finding that Ajoene has a strong, although transient, inhibitory effect on the activation of the endothelium induced by pig cells and its known anti‐platelet activity, it is suggested that this garlic compound could be useful to prevent the development of microangiopathy and thrombotic disorders seen in primates infused with pig cells.
Treatment with a short course of LF 15‐0195 and continuous cyclosporin A attenuates acute xenograft rejection in a rat‐to‐mouse cardiac transplantation model
Authors: Wang Hao , Hosiawa Karoline A. , Garcia Bertha , Shum Jeffrey B. , Dutartre Patrick , Kelvin David J. , Zhong Robert
Published: June 2003

Abstract: Searching for a novel immunosuppressive agent to effectively prevent acute vascular rejection (AVR) is essential for success in clinical xenotransplantation. We previously reported that Lewis rat hearts transplanted into BALB/c mice developed typical AVR in 6 days. The present study was undertaken to determine the efficacy of LF 15‐0195, a new immunosuppressive analog of 15‐deoxyspergualin in the prevention of AVR in a rat‐to‐mouse cardiac xenograft model. We transplanted 2‐week old Lewis rat hearts into BALB/c mice. Four groups were included in this study: untreated recipients and cyclosporin A (CsA) treated recipients were controls; LF 15‐0195 treated recipients or LF 15‐0195 combined with CsA treated recipients were experimental groups. Mouse recipients received either LF 15‐0195 2 mg/kg subcutaneously from day‐1 to post‐operative day 14, or CsA 15 mg/kg subcutaneously daily, from day 0 to endpoint rejection, or the two drugs in combination. We observed that high dose CsA did not inhibit AVR and the graft was rejected in 11.3 ± 1.9 days. Graft histology and immunohistology showed typical AVR, characterized by interstitial hemorrhage, intravascular fibrin deposition, thrombosis, and massive deposition of anti‐rat immunoglobulin G (IgG) and immunoglobulin M (IgM). Serum xenoreactive antibodies (xAbs) were markedly elevated in these animals as well. In contrast, we observed that treatment with LF 15‐0195 alone significantly prolonged graft survival to 19.3 ± 0.7 days. Notably, xAbs were significantly decreased and the rejection pattern of these grafts was cell‐mediated rejection (CMR), instead of AVR. When CsA was combined with LF 15‐0195, the graft mean survival time was further increased to 58.5 ± 17.3 days. Antibody production and T‐cell infiltration were significantly inhibited at the terminal stages of graft survival and pathology showed striking attenuation of both AVR and CMR. Sequential studies on days 6 and 14 demonstrated that LF 15‐0195 either alone or combined with CsA completely inhibited antibody production. However, intragraft infiltration by Mac‐1 positive cells including natural killer cells, macrophages and granulocytes in LF 15‐0195 treated recipients was similar to that of untreated recipients. We conclude that LF 15‐0195 effectively prevented AVR by markedly inhibiting the production of anti‐donor IgG xAbs. Also, treatment with short course LF 15‐0195 and continuous CsA significantly reduced T‐cell infiltration. Studies to test this therapy in inhibiting AVR in a pig‐to‐non‐human primate xenotransplantation model are underway.
Detection of porcine endogenous retrovirus in cultures of freshly isolated porcine bone marrow cells
Authors: McIntyre Matiza C. , Kannan Bhanumathi , Solano‐Aguilar Gloria I. , Wilson Carolyn A. , Bloom Eda T.
Published: June 2003

Abstract: Pigs are under consideration as possible sources of organs for xenotransplantation in humans. The induction of hematopoietic microchimerism through xenotransplantation of source animal hematopoietic cells has been suggested as a means to induce tolerance in potential recipients. Because all porcine cells contain genetic information for porcine endogenous retrovirus (PERV), coculture techniques, reverse transcriptase (RT) and reverse transcriptase‐polymerase chain reaction assays were used to determine whether infectious PERV is released from fresh porcine bone marrow cells cultured in the presence or absence of porcine cytokines. Human embryonic kidney cell line, HEK‐293 cells cocultured with porcine bone marrow cells were positive for PERV RNA but never became positive for viral RT activity, suggesting the PERV infection was not productive. In contrast, high levels of RT activity was detected in porcine ST‐IOWA cells after coculture, demonstrating that these cells became productively infected. PERV was released from cultured porcine bone marrow cells without stimulation, and combinations of the porcine hematopoietic cytokines, interleukin‐3, granulocyte macrophage‐colony stimulating factor and stem cell factor had no additional effect on the infectivity or in vitro tropism of released PERV virions.
Depletion of anti‐Gal antibodies by the intravenous infusion of Gal type 2 and 6 glycoconjugates in baboons
Authors: Teranishi Katsuhito , Alwayn Ian P.J. , Bühler Leo , Gollackner Bernd , Knosalla Christoph , Huck Jennifer , Duthaler Rudolf , Katopodis Andreas , Sachs David H. , Schuurman Henk‐Jan , Awwad Michel , Cooper David K.C.
Published: June 2003

Abstract: Background:  Natural anti‐Gal antibodies (NAb) to Gal epitopes play a key role in the rejection of pig cells or organs transplanted into primates. We have investigated the effect on NAb return after extracorporeal immunoadsorption (EIA) of the continuous intravenous (i.v.) infusion of (i) bovine serum albumin conjugated to Gal type 6 oligosaccharides (BSA‐Gal) or (ii) a poly l‐lysine backbone conjugated to Gal type 2 or 6 oligosaccharides (PLL‐Gal).

Methods:  Porcine mobilized peripheral blood progenitor cells (PBPC) obtained by leukapheresis from MHC‐inbred miniature swine (n = 9) were infused intravenously (i.v.) into baboons: Group 1 baboons (n = 4) received whole body and thymic irradiation, splenectomy, antithymocyte globulin, cobra venom factor, cyclosporine, mycophenolate mofetil, anti‐CD154mAb, porcine hematopoietic growth factors, and EIA before transplantation of high doses (2 to 4 × 1010 cells/kg) of PBPC; Group 2 baboons (n = 3) received the Group 1 regimen plus a continuous i.v. infusion of BSA‐Gal for up to 30 days; Group 3 baboons (n = 5) received the Group 1 regimen plus a continuous i.v. infusion of PLL‐Gal type 2 (n = 2) or both PLL‐Gal types 2 and 6 (n = 3) for up to 30 days.

Results:  Group 1: NAb returned to pre‐PBPC levels within 20–30 days, but there was no induction of antibody to Gal or non‐Gal determinants; Group 2: NAb was undetectable or at very low level during BSA‐Gal therapy. In one baboon, however, IgG to Gal type 2, but not to type 6, returned during BSA‐Gal therapy; Group 3: NAb was undetectable or at very low level during PLL‐Gal therapy. In two baboons that received PLL‐Gal type 2, NAb to Gal type 6, but not to type 2, returned during PLL‐Gal treatment. Two of five baboons, however, developed systemic infection. Four of five baboons died within 14 days; autopsy revealed focal hemorrhagic injury to their hearts, lungs, and small intestines, with histologic abnormalities that varied between animals from hemorrhage and/or thrombosis in some organs (heart, lungs, or intestine) to signs of infections (bacteria in intestine, cytomegalovirus in liver).

Conclusions:  (i) BSA‐Gal and PLL‐Gal therapy maintained depletion of NAb. (ii) Some heterogeneity in specificity of NAb was identified, indicating that the infusion of a combination of Gal type 2 and 6 glycoconjugates may be required. (iii) The addition of PLL‐Gal to the immunosuppressive regimen was associated with a high incidence of morbidity and mortality without a clear histopathologic entity underlying the cause of death.
Displacement amplitude of ultrasonic scaler inserts
Authors: Lea S.C. , Landini G. , Walmsley A.D.
Published: June 2003

Objectives: Scanning laser vibrometry is a noninvasive method of measuring the velocity, displacement amplitude and oscillation frequency of vibrating objects. The purpose of this study was to assess, using a scanning laser vibrometer (SLV), the performance of different designs of commercially available ultrasonic scaler generators by measuring the oscillatory characteristics of various scaler tips.

Methods: Four ultrasonic generators were tested (Cavitron SPS and Cavitron Select (Dentsply, York, PA, USA) and Piezon Master 400 and Mini Piezon (Electro‐Medical Systems, Switzerland)) with various designs of scaler tip. The tips were positioned with their anterior surface perpendicular to the direction of the laser. A graduated scale, placed over the manufacturer's power dial, enabled incremental power setting selection. For each power setting, the laser beam from the SLV was scanned over the surface of the oscillating tip.

Results: The ranges of longitudinal displacement amplitudes (in micrometres) were as follows: Mini Piezon (P‐tip): 12.90±1.44 to 44.03±7.80; Piezon Master 400 (P‐tip): 16.02±2.66 to 35.85±5.29; Cavitron SPS (TFI‐10 tip): 7.81±0.51 to 29.70±1.12; Cavitron Select (TFI‐10 tip): 13.13±1.44 to 33.77±4.27; Cavitron SPS (TFI‐3 tip): 5.50±0.46 to 31.35±3.62.

Conclusions: This study shows that there are differences between commercially available generators and that tip movement varies between tips of the same style as well as between the generator and tip design. Users of ultrasonic scalers should be made aware of this inherent variability that may influence clinical procedures.
Efficacy of subgingival calculus removal with Er:YAG laser compared to mechanical debridement: an in situ study
Authors: Eberhard Jörg , Ehlers Heiko , Falk Wolfgang , Açil Yahya , Albers Hans‐Karl , Jepsen Sören
Published: June 2003

Objectives: The aim of the present study was to compare the effectiveness of subgingival calculus removal from periodontally involved root surfaces with an Er:YAG laser compared to hand instrumentation in situ.

Methods: The mesial and distal surfaces of 30 single‐rooted teeth with untreated periodontitis were treated either by hand instrumentation (scaling and root planing (SRP)) or by Er:YAG laser irradiation with the aim of achieving a calculus‐free root surface. Subgingival plaque samples were obtained before and immediately after treatment for microbiological evaluation by culture and DNA probe analysis. The teeth were extracted and the residual calculus was measured by means of digitized planimetry. The morphology of the root surface was evaluated by scanning electron microscopy, and undecalcified sections were analyzed to determine residual calculus and the extent of cementum removal following both treatments.

Results: Following laser irradiation, 68.4±14.4% of the root surface was calculus free in contrast to 93.9±3.7% after SRP when both treatments were performed for the same time (2:15±1:00 min). If laser irradiation was allowed twice the time used for hand instrumentation, 83.3±5.7% of the root surface was devoid of calculus. The effectiveness of both treatments was not related to initial probing depth. The histologic evaluation showed that after SRP 73.2% of root dentin was completely denuded from cementum, while only a minimal cementum reduction was apparent after laser irradiation. Both treatment modalities resulted in a similar reduction of periodontopathogens.

Discussion: The present investigation could demonstrate the in vivo capability of the Er:YAG laser to remove calculus from periodontally involved root surfaces, although the effectiveness did not reach that achieved by hand instrumentation. The lack of cementum removal in contrast to SRP may qualify the laser as an alternative approach during supportive periodontal therapy.
Tumor necrosis factor‐alpha gene (TNF‐α) −1031/−863, −857 single‐nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese
Authors: Soga Yoshihiko , Nishimura Fusanori , Ohyama Hideki , Maeda Hiroshi , Takashiba Shogo , Murayama Yoji
Published: June 2003

Objectives: Tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) participate in the establishment of inflammatory lesions in periodontitis. High production of these cytokines may relate to the severity of periodontitis. There have already been several studies examining the association between periodontitis and single nucleotide polymorphisms (SNPs) that affect cytokine productivity. Recently, new SNPs of TNF‐α, −1031, −863 and −857, variants of which are observed in a relatively large proportion in Japanese, have been identified. The variant alleles of these SNPs have been suggested to be related to high TNF‐α production. For a better understanding of the genetic factors associated with the severity of periodontitis, further analysis including these newly identified SNPs is essential. In addition, previous reports on TNF‐α or IL‐1β SNPs associated with periodontitis were mainly for Caucasian populations. Therefore, the aim of this study is to examine the association between severe periodontitis in Japanese and the following SNPs: five in the TNF‐α gene promoter (−1031, −863, −857, −308, −238) and three in the IL‐1β gene (−511, −31, +3953).

Material and Methods: A total of 128 Japanese individuals were enrolled in this study. They were 64 patients with severe adult periodontitis and 64 healthy subjects. TNF‐α and IL‐1β SNPs were genotyped by polymerase chain reaction‐restriction fragment length polymorphism for all subjects. TNF‐α and IL‐1β production from LPS‐stimulated monocytes/macrophages was also measured for 15 healthy male subjects.

Results: TNF‐α production in TNF‐α−1031/−863 (linkage disequilibrated) or –857 SNP variant allele carriers tended to be elevated, and the frequency of subjects who carried at least one variant allele in TNF‐α–1031, –863 or –857 SNPs among severe periodontitis patients was significantly higher than in healthy subjects.

Conclusion: Since the frequency of subjects who carried at least one variant allele in TNF‐α–1031, –863 or –857 SNPs was higher in periodontitis patients than in healthy subjects, TNF‐α−1031, −863 and −857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.