bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+ T cells contribute to postischemic liver injury in mice by interacting with sinusoidal endothelium and platelets
Authors: Khandoga Andrej , Hanschen Marc , Kessler Julia S. , Krombach Fritz
Published: January 2006

The mechanisms by which T cells contribute to the hepatic inflammation during antigen-independent ischemia/reperfusion (I/R) are not fully understood. We analyzed the recruitment of T cells in the postischemic hepatic microcirculation

in vivo

and tested the hypothesis that T cells interact with platelets and activate sinusoidal endothelial cells, resulting in microvascular dysfunction followed by tissue injury. Using intravital videofluorescence microscopy, we show in mice that warm hepatic I/R (90/30-140 min) induces accumulation and transendothelial migration of CD4+, but not CD8+ T cells in sinusoids during early reperfusion. Simultaneous visualization of fluorescence-labeled CD4+ T cells and platelets showed that approximately 30% of all accumulated CD4+ T cells were colocalized with platelets, suggesting an interaction between both cell types. Although interactions of CD4+/CD40L−/− T cells with CD40L−/− platelets in wild-type mice were slightly reduced, they were almost absent if CD4+ T cells and platelets were from CD62P−/− mice. CD4 deficiency as well as CD40-CD40L and CD28-B7 disruption attenuated postischemic platelet adherence in the same manner as platelet inactivation with a glycoprotein IIb/IIIa antagonist and reduced neutrophil transmigration, sinusoidal perfusion failure, and transaminase activities. Treatment with an MHC class II antibody, however, did not affect I/R injury.

In conclusion,

we describe the type, kinetic, and microvascular localization of T cell recruitment in the postischemic liver. CD4+ T cells interact with platelets in postischemic sinusoids, and this interaction is mediated by platelet CD62P. CD4+ T cells activate endothelium, increase I/R-induced platelet adherence and neutrophil migration via CD40-CD40L and CD28-B7-dependent pathways, and aggravate microvascular/hepatocellular injury. (Hepatology 2006;43:306–315.)
The sources of parenchymal regeneration after chronic hepatocellular liver injury in mice
Authors: Vig Pamela , Russo Francesco P. , Edwards Robert J. , Tadrous Paul J. , Wright Nicholas A. , Thomas Howard C. , Alison Malcolm R. , Forbes Stuart J.
Published: January 2006

After liver injury, parenchymal regeneration occurs through hepatocyte replication. However, during regenerative stress, oval cells (OCs) and small hepatocyte like progenitor cells (SHPCs) contribute to the process. We systematically studied the intra-hepatic and extra-hepatic sources of liver cell replacement in the hepatitis B surface antigen (HBsAg-tg) mouse model of chronic liver injury. Female HBsAg-tg mice received a bone marrow (BM) transplant from male HBsAg-negative mice, and half of these animals received retrorsine to block indigenous hepatocyte proliferation. Livers were examined 3 and 6 months post-BM transplantation for evidence of BM-derived hepatocytes, OCs, and SHPCs. In animals that did not receive retrorsine, parenchymal regeneration occurred through hepatocyte replication, and the BM very rarely contributed to hepatocyte regeneration. In mice receiving retrorsine, 4.8% of hepatocytes were Y chromosome positive at 3 months, but this was frequently attributable to cell fusion between indigenous hepatocytes and donor BM, and their frequency decreased to 1.6% by 6 months, as florid OC reactions and nodules of SHPCs developed. By analyzing serial sections and reconstructing a 3-dimensional map, continuous streams of OCs could be seen that surrounded and entered deep into the nodules of SHPCs, connecting directly with SHPCs, suggesting a conversion of OCs into SHPCs.

In conclusion,

during regenerative stress, the contribution to parenchymal regeneration from the BM is minor and frequently attributable to cell fusion. OCs and SHPCs are of intrinsic hepatic origin, and OCs can form SHPC nodules. (Hepatology 2006;43:316–324.)
Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?
Authors: Zintzaras Elias , Stefanidis Ioannis , Santos Mauro , Vidal Francesc
Published: January 2006

Case–control studies that have investigated the association between alcoholism and alcohol-induced liver damage and the

ADH2

,

ADH3

,

CYP2E1

, and

ADLH2

polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of

ADH2

*

1

,

ADH3

*

2

, and

ALDH2

*

1

alleles and the risk of alcoholism (OR = 1.89 [95% CI 1.56–2.28], 1.32 [95% CI 1.12–1.57], and 4.35 [95% CI 3.04–6.23], respectively). The subsequent subgroup analyses showed association for ADH2*1 and ADH3*2 only in East Asians (OR = 2.23 [95% CI 1.81–2.74] and 1.91 [95% CI 1.45–2.53], respectively) and East Asian males (OR = 2.21 [95% CI 1.57–3.10], 1.69 [95% CI 1.10–2.59], respectively). In East Asian males, the OR for ALDH2*1 was 3.66 (95% CI 1.68–7.96). In Caucasians, sensitivity analysis revealed an association for ADH2*1 in alcoholism (OR = 1.62 [95% CI 1.22–1.89]). When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The

CYP2E1

polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant.

In conclusion

, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results.

Supplementary material for this article can be found on the HEPATOLOGY website (

http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html

).

(Hepatology 2006;43:352–361.)
Deaths on the liver transplant waiting list: An analysis of competing risks
Authors: Kim Ray W. , Therneau Terry M. , Benson Joanne T. , Kremers Walter K. , Rosen Charles B. , Gores Gregory J. , Dickson Rolland E.
Published: January 2006

The usual method of estimating survival probabilities, namely the Kaplan-Meier method, is suboptimal in the analysis of deaths on the transplant waiting list. Death, transplantation, and withdrawal from list must all be considered. In this analysis, we applied the competing risk analysis method, which allows evaluating these end points individually and simultaneously, to compare the risk of waiting list death across era, blood types, liver disease diagnosis, and severity (Model for End-stage Liver Disease; MELD). Of 861 patients registered on the waiting list at Mayo Clinic Rochester between 1990 and 1999, 657 (76%) patients underwent transplantation, 82 (10%) died while waiting, 41 (5%) withdrew from the list, and 81 (9%) patients were still waiting as of February 2002. The risk of death at 3 years was 10% by the competing risk analysis. During the study period, the median time to transplantation increased from 45 to 517 days. In univariate analyses, there was no significant difference in the risk of death by era of listing (

P

= .25) or blood type (

P

= .31), whereas the risk of death was significantly higher in patients with alcohol-induced liver disease and those with higher MELD score (

P

< .01). A multivariable analysis showed that after adjusting for MELD, blood type, and diagnosis, patients listed in the latter era had higher mortality.

In conclusion,

the competing risk analysis method is useful in estimating the risk of death among patients awaiting liver transplantation. (Hepatology 2006;43:345–351.)
Difference in cytotoxicity against hepatocellular carcinoma between liver and periphery natural killer cells in humans
Authors: Ishiyama Kohei , Ohdan Hideki , Ohira Masahiro , Mitsuta Hiroshi , Arihiro Koji , Asahara Toshimasa
Published: January 2006

In rodents, liver natural killer (NK) cells have been shown to mediate higher cytotoxic activity against tumor cells than do peripheral blood (PB) NK cells. However, such differences between liver and PB NK cells have not been extensively investigated in humans. The phenotypical and functional properties of NK cells extracted from liver perfusates at the time of living donor liver transplantation were investigated. The tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a critical molecule for NK cell–mediated anti-tumor cell killing, was not expressed by freshly isolated PB NK cells or by liver NK cells. Stimulation with interleukin (IL)-2, significantly up-regulated the expression of TRAIL on liver NK cells, but this effect was barely observed on PB NK cells. Donor liver NK cells showed the most vigorous cytotoxicity against HepG2, a hepatocellular carcinoma (HCC) cell line, after IL-2 stimulation (90.5% ± 2.2% at E: T = 10:1), compared with donor and recipient PB NK cells and recipient liver NK cells (64.8% ± 8.2%, 56.1% ± 8.9%, and 34.6% ± 7.5%, respectively). IL-2 stimulation resulted in an increased expression of killing inhibitory receptors on liver NK cells in parallel with TRAIL expression. Consistently, the cytotoxicities of IL-2–stimulated donor liver NK cells against self and recipient lymphoblasts were negligible.

In conclusion,

adoptive transfer of IL-2–stimulated NK cells extracted from donor liver graft perfusate could mount an anti-tumor response without causing toxicity against 1-haplotype identical recipient intact tissues. These findings present a concept to prevent recurrence of HCC after liver transplantation. (Hepatology 2006;43:362–372.)
Proteasome inhibition induces hepatic stellate cell apoptosis
Authors: Anan Akira , Baskin-Bey Edwina S. , Bronk Steven F. , Werneburg Nathan W. , Shah Vijay H. , Gores Gregory J.
Published: January 2006

Induction of hepatic stellate cell (HSC) apoptosis attenuates hepatic fibrosis, and, therefore, mechanisms to induce HSC cell death are of therapeutic interest. Proteasome inhibitors induce apoptosis in transformed cells, especially those cells dependent upon nuclear factor kappa B (NF-κB) activation. Because stimulated HSCs also trigger NF-κB activation, the aim of this study was to determine if proteasome inhibitors induce HSC apoptosis. The immortalized human HSC line, LX-2, and primary rat HSCs were treated with the proteasome inhibitors bortezomib and MG132. Both proteasome inhibitors induced HSC apoptosis. Proteasome inhibition blocked NF-κB activation and, more importantly, NF-κB inhibition by Bay11-7082–triggered HSC apoptosis. Activated HSC survival is dependent upon the NF-κB target gene A1, an anti-apoptotic Bcl-2 family member, as siRNA targeted knockdown of A1-induced HSC apoptosis. In contrast, proteasome inhibition–induced alterations in TRAIL, death receptor 5, and Bim could not be implicated in the apoptotic response. The relevance of these findings was confirmed in the bile-duct–ligated mouse where bortezomib reduced hepatic markers of stellate cell activation and fibrosis.

In conclusion

, proteasome inhibition is a potential therapeutic strategy for inducing HSC apoptosis and inhibiting liver fibrogenesis. (Hepatology 2006;43:335–344.)
Isolation and characterization of lipid microdomains from apical and basolateral plasma membranes of rat hepatocytes
Authors: Mazzone Amelia , Tietz Pamela , Jefferson John , Pagano Richard , LaRusso Nicholas F.
Published: January 2006

Canalicular bile is formed by the osmotic filtration of water in response to osmotic gradients generated by active transport at the apical and basolateral plasma membrane domains of hepatocytes. We recently demonstrated that mixed plasma membrane fractions isolated from rat hepatocyte couplets contain lipid microdomains (“rafts”) enriched in cholesterol and sphingolipids and AQP8 and 9. We isolated lipid microdomains from hepatocyte apical and basolateral plasma membrane domains using Triton X-100 as detergent, and characterized their lipid and protein composition. A Triton-insoluble band (“raft fraction”) at the 5%/30% sucrose interface in both apical and basolateral fractions was enriched for alkaline phosphatase (apical) and Na/K ATPase (basolateral) and was negative for amino peptidase-N. This detergent-insoluble band was also positive for caveolin-1 (a “raft” associated protein) and negative for clathrin (a “raft” negative protein). Lipid analysis showed that, the Triton-insoluble fraction was highly enriched in cholesterol and sphingolipids. Immunofluorescence staining on hepatocyte couplets for both caveolin-1 and cholera toxin B showed a punctate distribution on both the apical and basolateral plasma membranes, consistent with localized membrane microdomains. Dot blot analysis showed that the “raft” associated ganglioside GM1 was enriched in the detergent-insoluble fraction both domains. Furthermore, exposure of isolated hepatocytes to glucagon, a choleretic agonist, significantly increased the expression of AQP8 associated with the apical microdomain fractions but had no effect on AQP9 expression in the basolateral microdomain fractions.

In conclusion

, “rafts” represent target microdomains for exocytic insertion and retrieval of “flux proteins”, including AQPs, involved in canalicular bile secretion. (Hepatology 2006;43:287–296.)
Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger
Authors: Banales Jesús M. , Arenas Fabián , Rodríguez-Ortigosa Carlos M. , Sáez Elena , Uriarte Iker , Doctor Brian R. , Prieto Jesús , Medina Juan F.
Published: January 2006

Canalicular bile is modified along bile ducts through reabsorptive and secretory processes regulated by nerves, bile salts, and hormones such as secretin. Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR)–dependent Cl− efflux and subsequent biliary HCO3
− secretion, possibly via Cl−/HCO3
− anion exchange (AE). However, the contribution of secretin to bile regulation in the normal rat, the significance of choleretic bile salts in secretin effects, and the role of Cl−/HCO3
− exchange in secretin-stimulated HCO3
− secretion all remain unclear. Here, secretin was administered to normal rats with maintained bile acid pool via continuous taurocholate infusion. Bile flow and biliary HCO3
− and Cl− excretion were monitored following intrabiliary retrograde fluxes of saline solutions with and without the Cl− channel inhibitor 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) or the Cl−/HCO3
− exchange inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). Secretin increased bile flow and biliary excretion of HCO3
− and Cl−. Interestingly, secretin effects were not observed in the absence of taurocholate. Whereas secretin effects were all blocked by intrabiliary NPPB, DIDS only inhibited secretin-induced increases in bile flow and HCO3
− excretion but not the increased Cl− excretion, revealing a role of biliary Cl−/HCO3
− exchange in secretin-induced, bicarbonate-rich choleresis in normal rats. Finally, small hairpin RNA adenoviral constructs were used to demonstrate the involvement of the Na+-independent anion exchanger 2 (AE2) through gene silencing in normal rat cholangiocytes.

AE2

gene silencing caused a marked inhibition of unstimulated and secretin-stimulated Cl−/HCO3
− exchange.

In conclusion

, maintenance of the bile acid pool is crucial for secretin to induce bicarbonate-rich choleresis in the normal rat and that this occurs via a chloride–bicarbonate exchange process consistent with AE2 function. (Hepatology 2006;43:266–275.)
A digital micro‐mirror device‐based system for the microfabrication of complex, spatially patterned tissue engineering scaffolds
Authors: Lu Yi , Mapili Gazell , Suhali Gerry , Chen Shaochen , Roy Krishnendu
Published: January 2006

Our ability to create precise, pre‐designed, spatially patterned biochemical and physical microenvironments inside polymer scaffolds could provide a powerful tool in studying progenitor cell behavior and differentiation under biomimetic, three‐dimensional (3D) culture conditions. We have developed a simple and fast, layer‐by‐layer microstereolithography system consisting of an ultra‐violet light source, a digital micro‐mirror masking device, and a conventional computer projector, that allows fabrication of complex internal features along with precise spatial distribution of biological factors inside a single scaffold. Photo‐crosslinkable poly(ethylene glycol) diacrylates were used as the scaffold material, and murine bone marrow‐derived cells were successfully encapsulated or seeded on fibronectin‐functionalized scaffolds. Fluorescently‐labeled polystyrene microparticles were used to show the capability of this system to create scaffolds with complex internal architectures and spatial patterns. We demonstrate that precisely controlled pore size and shapes can be easily fabricated using a simple, computer‐aided process. Our results further indicate that multi‐layered scaffolds with spatially distributed factors in the same layer or across different layers can be efficiently manufactured using this technique. These microfabricated scaffolds are conducive for osteogenic differentiation of marrow‐derived stem cells, as indicated by efficient matrix mineralization. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Enterococcus faecalis‐mediated biomineralized biofilm formation on root canal dentine in vitro
Authors: Kishen A. , George S. , Kumar R.
Published: January 2006

Enterococcus faecalis is the most predominant bacteria in teeth with failed root canal therapy and is found to survive harsh conditions prevailing in the root canals of endodontically treated teeth. This study aims to investigate the interaction between E. faecalis and root canal dentine substrate. Towards this end, tooth specimens were prepared and divided into two groups. The tooth specimens in group 1 were incubated with E. faecalis for periods of 2‐, 4‐, and 6‐week intervals and the chemical composition of the biofilm was determined using X‐ray diffraction and Fourier transform infrared (FTIR) spectroscopy. The tooth specimens in group 2 were incubated with E. faecalis for a period of 6 weeks and the topography and ultrastructure of the biofilm were examined using scanning electron microscopy (SEM), light microscopy, and laser confocal scanning microscopy. The sediments formed from the bacterial interaction on the dentine (in group 1) were also examined by SEM and FTIR. These experiments highlighted different stages in the interaction of E. faecalis with root canal dentine. Further, a bacterial‐induced apatite reprecipitation on mature biofilm was also observed. This ability of E. faecalis to form such calcified biofilm on root canal dentine may be a factor that contributes to their persistence after endodontic treatment. 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Poly(D,L‐lactic acid) coated 45S5 Bioglass®‐based scaffolds: Processing and characterization
Authors: Chen Q.Z. , Boccaccini A.R.
Published: January 2006

A comparative investigation has been carried out on the mechanical properties and bioactivity of Bioglass®‐based foams, before and after applying a poly(D,L‐lactic acid) (PDLLA) coating layer on the foam struts. It was found that the bioactivity of foams upon immersion in simulated body fluid (SBF) was maintained in the PDLLA‐coated foams; however, the transformation kinetics in SBF of the crystalline phase (Na2Ca2Si3O9) in the foam struts to an amorphous calcium phosphate phase was retarded by PDLLA coating. The compressive and three‐point bending strengths of the Bioglass®‐based foams were slightly improved by the PDLLA‐coating, and the work‐of‐fracture of the foams was considerably enhanced, as indicated by stress–strain curves. Immersion in SBF for 4 weeks led to a large decrease of the mechanical strength of as‐sintered foams decreased (from 0.3 to 0.03 MPa), because of the transformation of the crystalline phase to an amorphous calcium phosphate. On the other hand, the mechanical strength was well‐maintained in PDLLA‐coated foams after immersion in SBF for 8 weeks. This behavior was attributed to the in‐situ formation of a nanocomposite PDLLA/calcium phosphate film on the strut surfaces upon immersion in SBF. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Theoretical study on structures and stabilities of [H,Ge,C,N]
Authors: Wang Qiang , Ding Yi‐Hong , Xie Hong‐Bin , Sun Chia‐Chung
Published: January 2006

Theoretical investigations are performed for the first time on the simplest hydrogenated germanium cyanide [H,Ge,C,N], whose analogs [H,C2,N] and [H,Si,C,N] have been detected in space and laboratory, respectively. The detailed potential energy surfaces in both singlet and triplet states are constructed at the CCSD(T)/6‐311+G(3df,2p)//B3LYP/6‐31G(d)+ZPVE level, including 18 minimum isomers and 26 interconversion transition states. The former three low‐lying and kinetically stabilized isomers are HGeCN 11 (0.0 kcal/mol), HGeNC 12 (5.1 kcal/mol), and cyclic cCHNGe17 (11.1 kcal/mol). In addition, five isomers HCNGe 13 (33.8), HNCGe 15 (29.8), cNHCGe 18 (37.9), HGeCN 31 (30.1), and HNCGe 35 (26.5) each have considerable barriers, despite their high energies. Future laboratory characterization and astrophysical detection of the eight [H,Ge,C,N] isomers, especially the former three low‐lying species 11, 12, and 17, are highly recommended. The accurate spectroscopic data at the QCISD/6‐311G(d,p) level are provided. For some species, the CBS‐QB3 calculations are also performed. Wherever possible, comparisons with the analogous [H,C2,N] and [H,Si,C,N] are made on the structural, energetic, and bonding properties. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 505–514, 2006
Pleistocene fluvial sediments, palaeontology and archaeology of the upper River Thames at Latton, Wiltshire, England
Authors: Lewis S. G. , Maddy D. , Buckingham C. , Coope G. R. , Field M. H. , Keen D. H. , Pike A. W. G. , Roe D. A. , Scaife R. G. , Scott K.
Published: January 2006

Pleistocene fluvial sediments of the Northmoor Member of the Upper Thames Formation exposed at Latton, Wiltshire, record episodic deposition close to the Churn–Thames confluence possibly spanning the interval from Marine Isotope Stages (MIS) 7 to 2. The sequence is dominated by gravel facies, indicating deposition by a high‐energy, gravel‐bed river. A number of fine‐grained organic sediment bodies within the sequence have yielded palaeoenvironmental and biostratigraphical data from Mollusca, Coleoptera, vertebrates, pollen and plant macrofossils. The basal deposit (Facies Association A) contains faunal material indicating temperate conditions. Most of the palaeontological evidence including a distinctive small form of mammoth (Mammuthus cf. trogontherii), together with the U‐series age estimate of >147.4 ± 20 kyr suggest correlation with MIS 7. The overlying deposits (Facies Associations B and C) represent deposition under a range of climatic conditions. Two fine‐grained organic deposits occurred within Association B; one (Association Ba) in the northern part of the pit as a channel fill and the other (Association Bb) in its southern part as a scour‐fill deposit. The coleopteran assemblages from Ba, indicate that it accumulated under temperate oceanic conditions, while Bb, which also yielded a radiocarbon age estimate of 39 560 ± 780 14C yr BP, was formed under much colder and more continental climatic conditions. The sequence is considered to represent deposition within an alluvial fan formed at the Churn–Thames confluence; a depositional scenario which may account for the juxtaposition of sediments and fossils of widely differing age within the same altitudinal range. Copyright © 2006 John Wiley & Sons, Ltd.
Role of bridging diamine linkers on the rate of ligand substitution in a series of dinuclear PtII complexes
Authors: Jaganyi D. , Munisamy V. M. , Reddy D.
Published: January 2006

A series of dinuclear platinumII complexes of the type [{trans‐Pt(H2O)(NH3)2}2‐NH2(CH2)nH2N]4+ (where n = 2, 3, 4, and 6) were synthesized to investigate the influence of the bridging diamine linker on the reactivity of the platinum centers. The pKa values were determined, and the rates of substitution of the aqua moieties by a series of neutral nucleophiles viz. thiourea, 1,3‐dimethyl‐2‐thiourea, and 1,1,3,3‐tetramethyl‐2‐thiourea were studied as a function of concentration and temperature. All reactions studied gave excellent fits to a single exponential and obeyed the simple rate law, kobs=k2[Nu]. Negative activation entropies support an associative mode of substitution. The results obtained suggest that the rate of substitution is definitely influenced by the length of the diamine chain, with the rate of substitution decreasing as the length of the diamine chain increases. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 38: 202–210, 2006
Complications of laser dermatologic surgery
Authors: Willey Andrea , Anderson R. Rox , Azpiazu Jose L. , Bakus Abnoeal D. , Barlow Richard J. , Dover Jeffrey S. , Garden Jerome M. , Kilmer Suzanne L. , Landa Nerea , Manstein Dieter , Ross E. Victor , Sadick Neil , Tanghetti Emil A. , Yaghmai Dina , Zelickson Brian D.
Published: January 2006

Background and Objective

Innovations in lasers, light and radiofrequency devices have allowed for improved therapeutic efficacy and safety and the ability to treat patients with an ever‐increasing number of medical and aesthetic indications. Safety remains a primary concern and the timely communication of complications and their management is vital to insure that treatments be as safe as possible. The purpose of this report on the Proceedings of the First International Laser Surgery Morbidity Meeting is to provide laser experts the opportunity to present and discuss complications that their patients have experienced and how they were successfully managed.

Methods

Laser experts were invited to present complications of laser, light, and radiofrequency treatments that their patients have experienced and to discuss the potential mechanisms leading to the complications their management and final outcomes.

Results

Nineteen unique cases are presented and the clinical management of each case discussed. Eighteen sets of pre‐ and post‐operative photos are presented.

Conclusion

This report shows that even experts, with extensive experience using light‐based therapies, can and do have patients who develop complications. Sound clinical judgment, and knowing how to avoid complications and their timely post‐operative management, is essential to insure optimal therapeutic outcome. Lasers Surg. Med. 38:1–15, 2006. © 2006 Wiley‐Liss, Inc.
Learning microsurgical suturing and knotting techniques: comparative data
Authors: Furka Istvan , Brath Endre , Nemeth Norbert , Miko Iren
Published: January 2006

Correctly performed surgical sutures are the basis of surgical safety. This retrospective survey was conducted among participants (n = 263) taking graduate and postgraduate courses between 2000–2004. Placement of sutures, time to perform knotting, safety of knots, and quality of knot stability were tested. None of the students had been previously instructed in microsurgical techniques. At the beginning of the training program, 90–95% of participants damaged the suturing thread at several places. By the end of the course, knotting times significantly decreased in both groups. Graduates decreased their time from 6.8 ± 2.34 min to 3.28 ± 0.71 min (mean ± standard error of the mean), and postgraduates decreased their time from 5.02 ± 3.25 min to 1.54 ± 0.54 min (mean ± standard error of the mean). In our opinion, “mass training” to teach the basics of microsurgery is not a good approach. Instead, individual training should be provided, as tutors offer invaluable advice, and adjust almost each stitch and knot during teaching sessions. © 2006 Wiley‐Liss, Inc. Microsurgery 26: 4–7, 2006.
Use of nonpenetrating vascular closure staples in feline renal transplantation
Authors: Iwai Satomi , Endo Kaoru , Hakamata Yoji , Gregory Clare R. , Kobayashi Eiji
Published: January 2006

Renal transplantation is a potential treatment for irreversible renal failure in pet cats. Our aim is to reduce warm ischemic time by using nonpenetrating vascular closure staples (VCS), thereby improving graft survival. Experimental cats were divided into the VCS group (n = 4; autotransplantation) or suture group (n = 6; allotransplantation). The renal artery was anastomosed with the external iliac artery in an end‐to‐end fashion, and the renal vein was attached to the external iliac vein in an end‐to‐side fashion. Warm ischemic time as well as arterial and venous anastomotic times were measured. Cats in the suture group were administrated cyclosporine and prednisolone orally after transplantation. Ischemic and anastomotic times in the VCS group were significantly reduced compared with the suture group. Two of 6 allografts had a ureteral anastomotic stricture, and 4 allografts were rejected. Histological findings of autografts showed normal structure. In conclusion, VCS staples were useful in feline renal transplantation. © 2006 Wiley‐Liss, Inc. Microsurgery 26: 13–16, 2006.
Immune regulatory activity of liver‐derived dendritic cells generated in vivo
Authors: Wu Wenhan , Zheng Ning , Wang Yalan , Fung John J. , Lu Lina , Qian Shiguang
Published: January 2006

Hepatic tolerance is demonstrated by spontaneous acceptance of liver allografts in mice. Hepatic dendritic cells (DC) play a crucial role in determining immunity or tolerance. In this study, we adopted an approach to transfect gene(s) into the mouse liver by tail‐vein injection of plasmid‐carrying genes. Transfection with GM‐CSF expanded liver CD11c+ myeloid DC (LMDC), while liver B220+CD11c− lymphoid DC (LLDC) were expanded after transfection of IL‐3 and CD40L. Flow analysis revealed that these liver DC subsets were phenotypically mature following overnight culture. However, in contrast to LMDC, LLDC induced hyporesponsiveness in allogeneic T‐cells, with suppressed secretion of both IL‐2 and IFN‐γ, and prolonged cardiac allograft survival. This immune regulatory DC population in the liver may play a role in modulating T‐cell immunity in the liver. © 2006 Wiley‐Liss, Inc. Microsurgery 26: 17–20, 2006.
Heme oxygenase 1 expression in postischemic reperfusion liver damage: effect of L‐Arginine
Authors: Lanteri Raffaele , Acquaviva Rosaria , Di Giacomo Claudia , Caltabiano Rosario , Li Destri Giovanni , Vanella Luca , Santangelo Marco , Lanzafame Salvatore , Di Cataldo Antonio
Published: January 2006

Ischemia/reperfusion (I/R) injury is a multifactorial process that affects liver function after transplantation and resectional surgery. Alterations in hepatic microcirculation and decreased hepatic flow can cause local hypoxia and consequently liver damage, which is worsened by reperfusion. The aim of this study was to evaluate if treatment with L‐arginine improved hepatic function in rats with I/R injury. Animals were treated with L‐arginine, ischemized for 30 min, and reperfused for 3 h. Plasmatic levels of GOT, GPT, lipid hydroperoxides (LOOH), and total thiol groups (RSH) were evaluated. In addition, we analyzed hepatic LOOH and RSH levels, DNA fragmentation, heme oxygenase 1 (HO‐1) expression, and histological modifications. Our results demonstrate a significant improvement in hepatic function of I/R rats compared to the control group. Treatment with L‐arginine increased the expression of HO‐1. These data suggest that L‐arginine could be useful in preventing oxidative damage during hepatic surgery. © 2006 Wiley‐Liss, Inc. Microsurgery 26: 25–32, 2006.
Microvascular and epithelial permeability measurements in laboratory animals
Authors: Szabo Andrea , Menger Michael D. , Boros Mihaly
Published: January 2006

Disruption of the mucosal permeability barrier is an acute life‐threatening consequence of intestinal transplantation. The major aim of organ preservation techniques is to maintain the mucosal barrier and its function. Thus, assessment of microvascular and epithelial permeability is an important tool to determine the efficacy of therapeutic interventions. The use of murine models is particularly advantageous, as numerous immunological approaches (e.g., monoclonal antibodies) and genetically modified animal strains have been developed. Large animal models are also useful because they allow online detection of mucosal permeability changes. In this review, we summarize the available methodologies for measuring microvascular and epithelial permeability in the intestines of laboratory animals. We describe the advantages of various photometric and intravital microscopic methods for the assessment of microvascular permeability. Techniques that determine the inward and outward direction of mucosal permeability changes (including radioenzymatic, fluorimetric, and intravital microscopy methods) are also discussed. © 2006 Wiley‐Liss, Inc. Microsurgery 26: 50–53, 2006.
Solving parabolic problems using local defect correction in combination with the finite volume method
Authors: Minero R. , Anthonissen M.J.H. , Mattheij R.M.M.
Published: January 2006

We present a method for solving partial differential equations characterized by highly localized properties in which the local defect correction (LDC) algorithm for time‐dependent problems is combined with a finite volume discretization. At each time step, LDC computes a numerical solution on a composite grid, a union of a global uniform coarse grid and a local uniform fine grid. The main feature of the method is that the discrete conservation property, typical of the finite volume approach is preserved on the composite grid. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2006
The method of fundamental solutions with eigenfunction expansion method for nonhomogeneous diffusion equation
Authors: Young D. L. , Chen C. W. , Fan C. M. , Tsai C. C.
Published: January 2006

In this article we describe a numerical method to solve a nonhomogeneous diffusion equation with arbitrary geometry by combining the method of fundamental solutions (MFS), the method of particular solutions (MPS), and the eigenfunction expansion method (EEM). This forms a meshless numerical scheme of the MFS‐MPS‐EEM model to solve nonhomogeneous diffusion equations with time‐independent source terms and boundary conditions for any time and any shape. Nonhomogeneous diffusion equation with complex domain can be separated into a Poisson equation and a homogeneous diffusion equation using this model. The Poisson equation is solved by the MFS‐MPS model, in which the compactly supported radial basis functions are adopted for the MPS. On the other hand, utilizing the EEM the diffusion equation is first translated to a Helmholtz equation, which is then solved by the MFS together with the technique of the singular value decomposition (SVD). Since the present meshless method does not need mesh generation, nodal connectivity, or numerical integration, the computational effort and memory storage required are minimal as compared with other numerical schemes. Test results for two 2D diffusion problems show good comparability with the analytical solutions. The proposed algorithm is then extended to solve a problem with irregular domain and the results compare very well with solutions of a finite element scheme. Therefore, the present scheme has been proved to be very promising as a meshfree numerical method to solve nonhomogeneous diffusion equations with time‐independent source terms of any time frame, and for any arbitrary geometry. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2006
Evaluation of semi‐quantitative scoring system for metaiodobenzylguanidine (mIBG) scans in patients with relapsed neuroblastoma
Authors: Messina Julia A. , Cheng Su‐Chun , Franc Benjamin L. , Charron Martin , Shulkin Barry , To Bao , Maris John M. , Yanik Gregory , Hawkins Randall A. , Matthay Katherine K.
Published: January 2006

Background

The purpose of this study was to determine the accuracy of two semi‐quantitative scoring systems to assess response to 131I‐metaiodobenzylguanidine (mIBG) therapy in recurrent neuroblastoma.

Procedures

Diagnostic mIBG scan pairs (n = 57) were collected for patients who underwent 131I‐mIBG therapy for relapsed neuroblastoma. Two scoring systems were designated: Method 1, which divided the body into nine segments to view osteomedullary lesions with an additional tenth segment to assess soft tissue involvement; and Method 2, which divided the body into seven segments without a corresponding compartment for soft tissue involvement. Four nuclear medicine physicians independently assigned extension and intensity scores utilizing both methods, and separately recorded their impression of whether the post‐therapy scan had improved, not changed, or worsened. Inter‐ and intra‐observer concordance and correlation with overall response and progression‐free survival (PFS) were performed.

Results

Method 1 produced the highest inter‐observer concordance and was used to calculate the relative extension scores (post‐therapy score divided by pre‐therapy score), which correlated significantly with overall response. Patients who achieved complete response (CR) or partial response (PR) (n = 21) had lower relative extension scores, compared to those without response (P < 0.001). The readers' overall impression associated highly (P < 0.001) with the relative extension scores though results were less quantitative. Concordance was higher if initial scores were >5. Relative extension score did not predict PFS.

Conclusion

Semi‐quantitative scoring of mIBG scans provides a more reliable method of assessing response in patients with relapsed neuroblastoma than qualitative impression. The reproducibility and high inter‐observer concordance makes mIBG score an important component of overall response criteria in patients with recurrent neuroblastoma. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
Protein chip based miniaturized assay for the simultaneous quantitative monitoring of cancer biomarkers in tissue extracts
Authors: Weissenstein Ulrike , Schneider Michael J. , Pawlak Michael , Cicenas Jonas , Eppenberger‐Castori Serenella , Oroszlan Peter , Ehret Sabine , Geurts‐Moespot Anneke , Sweep Fred C. G. J. , Eppenberger Urs
Published: January 2006

A multiplexed fluorescence immunoassay using a novel planar waveguide technology‐based microarray system, ZeptoMARK (Zeptosens), was developed to detect simultaneously urokinase‐type plasminogen activator (uPA), plasminogen activator inhibitor‐1 (PAI‐1), and vascular endothelial growth factor (VEGF) in extracts of breast cancer tissues. The three analytes assay was cross‐validated with single‐analyte ELISA/chemiluminescence immunosorbent assay tests, revealing good correlations and enhanced assay sensitivities (LODs) of 1 pg/mL for uPA, 33 pg/mL for PAI‐1, and 1 pg/mL for VEGF. Values were well within the 80–120% limits for assay recovery and within the ±20% limits for assay precision. The uPA, PAI‐1, and VEGF results obtained from 50 breast cancer cytosols using the protein array system demonstrated that the microarray‐based multiplexed assay is a sensitive and robust tool to be used for the simultaneous quantification of cancer markers in small breast cancer tissue samples (core biopsies). The miniaturized, multiplexed assay format has a potential to be used for the quantitative analysis of a larger set of validated markers with significance in disease management.
Improvement of α‐tocopherols long‐term efficiency by modeling its heterogeneous natural environment in polyethylene
Authors: Strandberg Clara , Albertsson Ann‐Christine
Published: January 2006

The natural antioxidant vitamin E (α‐tocopherol) is of interest to use in packaging applications to decrease the amount of toxic products migrating into food and drugs. We have earlier shown that the long‐term efficiency of α‐tocopherol in polyethylene (PE) films is poor. α‐Tocopherol is located in the lipid phase of the cell in vivo and it has been revealed that it is more efficient in a polar substrate. PE is more hydrophobic and homogenous than the heterogeneous and hydrophilic lipid phase. Three different additive systems were investigated to model α‐tocopherols heterogeneous natural environment in PE. Two of these had carboxylic acid groups, EAA and polyTRIM/PAA core‐shell particles (Core), and the third, oat starch, had no carboxylic acid groups. The materials were thermally aged and characterized by chemiluminescence (CL), FTIR, chromatography, and thermal analysis. The EAA system as well as the Core system improved the antioxidant properties of α‐tocopherol in PE, and the Core system had the best performance. We know that starch has stabilizing properties in PE, but it had no effect on the efficiency of α‐tocopherol. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1660–1666, 2006
Interaction between mammalian glyceraldehyde‐3‐phosphate dehydrogenase and L‐lactate dehydrogenase from heart and muscle
Authors: Svedružić Željko M. , Spivey H. Olin
Published: January 2006

The exceptionally high protein concentration in living cells can favor functional protein–protein interactions that can be difficult to detect with purified proteins. In this study we describe specific interactions between mammalian D‐glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) and L‐lactate dehydrogenase (LDH) isozymes from heart and muscle. We use poly(ethylene‐glycol) (PEG)‐induced coprecipitation and native agarose electrophoresis as two independent methods uniquely suited to mimic some of the conditions that can favor protein–protein interaction in living cells. We found that GAPDH interacts with heart or muscle isozymes of LDH with approximately one‐to‐one stoichiometry. The interaction is specific; GAPDH shows interaction with two LDH isozymes that have very different net charge and solubility in PEG solution, while no interaction is observed with GAPDH from other species, other NAD(H) dehydrogenases, or other proteins that have very similar net charge and molecular mass. Analytical ultracentrifugation showed that the LDH and GAPDH complex is insoluble in PEG solution. The interaction is abolished by saturation with NADH, but not by saturation with NAD+ in correlation with GAPDH solubility in PEG solution. The crystal structures show that GAPDH and LDH isozymes share complementary size, shape, and electric potential surrounding the active sites. The presented results suggest that GAPDH and LDH have a functional interaction that can affect NAD+/NADH metabolism and glycolysis in living cells. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Study of large magnetoresistance of thin polycrystalline Bi films annealed at critical temperatures
Authors: Tolutis R. A. , Balevičius S.
Published: January 2006

This paper reports an investigation of the large magnetoresistance (MR) of 0.3–1.5 µm thick polycrystalline Bi films deposited in vacuum on non‐crystalline substrates and annealed at critical temperatures. The occurrence of critical temperatures is associated with intensive growth of crystallites. It is demonstrated that such films consist of large 50–200 µm high‐quality crystallites and exhibit a large transverse MR. At temperatures higher than 77 K the magnitude of the MR can exceed that of epitaxial Bi films. The experimental results are interpreted on the basis of a polycrystalline Bi thin‐film model. The data suggest that in Te‐doped Bi films the MR can be larger than that in pure Bi films. It is found that the grain‐boundary scattering is weak. However, there exist rather isotropic extra carrier scattering channels which reduce the anisotropy of electrical conductivity and MR. The relative importance of this extra scattering changes with temperature. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Highly ordered magnetic multilayer Ni/Cu nanowires
Authors: Liu R. S. , Chang S. C. , Hu S. F. , Huang C. Y.
Published: January 2006

Highly ordered nanowires with multilayer of Ni/Cu, have been successfully prepared by pulsed chemical electrodeposition into nanoporous alumina membrane. The diameter (ranging from 30 to 100 nm) of wires can be easily controlled by pore size of alumina. The applied potential and the duration of each potential square pulse determine the thickness of the metal layers. The nanowires have been characterized by transmission electron microscopy (TEM), magnetic force microscopy (MFM), and vibrating sample magnetometer (VSM) measurements. From the result of MFM analysis, the magnetic multilayer nanowire indicates unique magnetic property. The MFM images indicate that every ferromagnetic layer separated by Cu layer was present as single‐domain magnet. The results are demonstrated that this type of nanowires has a potential to the application of magnetic nanodevices. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Interface thermal resistance of nanostructured FeCoCu film and Si substrate
Authors: Nikolaenko Yuri M. , Medvedev Yuri V. , Genenko Yuri A. , Ghafari Mohammad , Hahn Horst
Published: January 2006

Results of measurement of thermal resistance (RFS ) of film substrate interface of 10 nm (Fe1–x Cox )1–y Cuy film on Si substrate with 50 nm SiO2 sublayer are presented. The estimated magnitude is two orders greater then RFS of epitaxial manganite films on StTiO3 substrate with and without sublayer. The significant increase of RFS is explained by granular structure of film with average size of grain about 10 nm. In this case the additional thermal barier in the film‐substrate interface is appeared. It provides the change of regime of phonons propagation from ballistic to diffusion one. The principle possibility of variation of RFS in wide range as a task of nanotechnology is discussed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Anxiolytic effects of a combination of Melissa ofcinalis and Valeriana ofcinalis during laboratory induced stress
Authors: Kennedy David O. , Little Wendy , Haskell Crystal F , Scholey Andrew B.
Published: January 2006

Objective:

Melissa ofcinalis (lemon balm) and Valeriana ofcinalis (valerian) have been used both traditionally and contemporaneously as mild sedatives, anxiolytics and hypnotics. Recent research has suggested that both may attenuate laboratory induced stress. As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory‐induced stress.

Methods:

In this double‐blind, placebo‐controlled, randomized, balanced cross‐over experiment, 24 healthy volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing M. ofcinalis and V. ofcinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. Modulation of mood and anxiety were assessed during pre‐dose and 1 h, 3 h and 6 h post‐dose completions of a 20 min version of the Dened Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed.

Results:

The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety. However, the highest dose (1800 mg) showed an increase in anxiety that was less marked but which reached signicance during one testing session. In addition, all three doses led to decrements in performance on the Stroop task module within the battery, and the two lower doses led to decrements on the overall score generated on the DISS battery.

Conclusions: These results suggest that a combination of Melissa ofcinalis and Valeriana ofcinalis possesses anxiolytic properties that deserve further investigation. Copyright © 2006 John Wiley & Sons, Ltd.
Botanical therapies in chronic fatigue
Authors: Tharakan Binu , Manyam Bala V.
Published: January 2006

Chronic fatigue often occurs in aging and in various neurological, psychiatric and systemic diseases. The available therapies in modern medicine are limited. The exploration of potential alternative therapies from traditional medicine is reviewed, as there are several botanicals with experimental evidence of efcacy based on animal models and clinical studies. Copyright © 2006 John Wiley & Sons, Ltd.