bluuebunny/crossref_metadata_2025 huggingface dataset:
Paravertebral Block Anesthesia for Inguinal Hernia Repair
Authors: Weltz Christina R. , Klein Stephen M. , Arbo John E. , Greengrass Roy A.
Published: March 2003

Abstract

Choice of anesthesia for inguinal hernia repair remains a controversial topic. Local anesthesia has been described in the literature as the optimal technique, however general and spinal anesthesia are commonly used in practice despite well‐known complications and side effects. The regional technique of paravertebral block has been successfully used at our institution for the operative treatment of breast cancer. Its attributes are prolonged sensory block with minimization of postoperative pain, reduction of nausea and vomiting, shortened hospital stay, patient satisfaction, and rapid return to normal activities. These features are desirable in the practice of ambulatory hernia surgery; hence we initiated the use of thoracic/lumbar paravertebral block for that surgical procedure. Paravertebral block anesthesia was performed on 30 consecutive patients. Block placement took an average of 12.3 minutes, in six cases repeat injection at one or two spinal levels was required due to incomplete blockade. Paravertebral block achieved effective anesthesia in 28 of 30 cases; conversion to general anesthesia was performed for two failed blocks. We are reporting postoperative data on the 28 completed blocks. Supplementation of intravenous sedation or injection of local anesthesia successfully treated transient intraoperative pain in 10 cases. Epidural extension of anesthesia resulting in lower limb numbness and motor weakness delayed the discharge of two patients. There were no other complications of anesthesia and no cases of urinary retention. Time to onset of pain averaged 15 hours, while duration of sensory block was 13 hours. Patients were prescribed a standing order of naproxen 500 mg b.i.d. for 4 days regardless of pain; supplemental oral narcotic use during the 48 hours following surgery averaged 3.5 tablets, with 6 patients not requiring any narcotic. Ninety‐six percent of patients scheduled for ambulatory surgery were discharged from the postanesthesia care unit, with an average stay of 2.5 hours. Employed patients returned to work on day 5.5 (range 3–10 days); patients who were not employed returned to regular activities in 5.8 days (range 1–14 days). Eighty‐two percent of patients reported being “very satisfied” with the anesthetic technique.
Intraoperative Imprint Cytologic Assessment of the Sentinel Node for Early Breast Cancer
Authors: Bochner Melissa A. , Farshid Gelareh , Dodd Thomas J. , Kollias James , Gill P. Grantley
Published: March 2003

Abstract

An increasing number of patients are undergoing sentinel node biopsy alone for axillary staging of early breast cancer. A reliable method for evaluating the status of the sentinel node intraoperatively would allow patients with sentinel node metastases to undergo immediate rather than delayed axillary clearance. Sentinel nodes in 53 consecutive patients were examined by intraoperative imprint cytology. When compared with subsequent analysis by hematoxylin‐eosin staining and immunohistochemistry, the accuracy of imprint cytology for the detecting nodal metastases was 81.1%; the false negative rate was 47.0%, and there were no false positives. Results were made available to the operating surgeon within a mean time of 25 minutes. All but one of the false negatives involved micrometastatic deposits of less than 0.1 mm. Intraoperative imprint cytologic examination of the sentinel node is a useful technique that can be performed efficiently and without loss of nodal tissue for subsequent analysis. With the use of this technique, more than 50% of lymph node‐positive patients would potentially be spared a second operation.
Parathyroid Adenomas versus Four‐gland Hyperplasia as the Cause of Primary Hyperparathyroidism in Patients with Prolonged Lithium Therapy
Authors: Awad Samir S. , Miskulin Judiann , Thompson Norman
Published: March 2003

Abstract

Chronic lithium therapy in patients with affective psychiatric disorders has been implicated as the cause of hypercalcemia and primary hyperparathyroidism. Our objective was to evaluate whether primary hyperparathyroidism was caused by an adenoma or four‐gland hyperplasia. The medical records of 15 patients with affective psychiatric disorders who were treated with chronic lithium therapy from 1982 to 1997, all of whom were operated on for primary hyperparathyroidism, were reviewed. Data on age, symptoms, duration of lithium therapy, pre‐ and postoperative calcium levels, and parathyroid hormone levels were collected. Parathyroid histology for each patient was independently and blindly reviewed. The mean age was 58 ± 10 years, the mean duration of lithium therapy 10.7 ± 6 years, and the mean preoperative calcium level 11.7 ± 0.5 mg/dl. All patients underwent bilateral neck exploration with selective resection of enlarged glands. Of the 15 patients, 14 (92%) had adenomas (11 single, 3 double), and 1 (8%) had four‐gland hyperplasia. All patients were rendered eucalcemic, with a postoperative calcium level of 9.2 ± 0.5 mg/dl (p < 0.005). All patients resumed their lithium therapy, with 1 of 15 patients developing recurrent hyperparathyroidism 2 years following the first operation; this patient required reexploration, at which time an adenoma was resected. In our experience hyperparathyroidism in patients who have undergone prolonged therapy with lithium is associated with a high incidence of parathyroid adenomas versus four‐gland hyperplasia. This suggests that lithium selectively stimulates growth of parathyroid adenomas in susceptible patients, who are best treated with adenoma excision rather than subtotal parathyroidectomy.
Promoter analysis of a medaka fish intestinal guanylyl cyclase gene
Authors: Nakauchi Mina , Suzuki Norio
Published: March 2003

We characterized the promoter activity of a medaka fish intestinal guanylyl cyclase gene, OlGC6, by assay of enzyme activity in response to various promoter–luciferase fusion gene constructs introduced into CACO‐2 cells and medaka fish embryos. A transient transfection assay of the various fusion gene constructs showed that the nucleotides between −98 and −89 in the 5′‐flanking region of the OlGC6 gene are essential for transcription of the OlGC6 gene in CACO‐2, and that the OlGC6 gene fragment between −98 and +50 is sufficient to drive gene expression in the medaka fish intestine. An electrophoretic mobility shift assay and ultraviolet (UV) cross‐linking experiments demonstrated that a nuclear protein from CACO‐2 cells and the adult medaka fish intestinal cells binds specifically to the AGACCTTTGC nucleotides in the regulatory element.
Mutational suppression of transferrin receptor shedding can be compensated by distinct metalloproteases acting on alternative sites
Authors: Dassler Katrin , Kaup Matthias , Tauber Rudolf , Fuchs Hendrik
Published: March 2003

The human transferrin receptor (TfR) is proteolytically cleaved at R100 within the juxtamembrane stalk and to a lesser extent at an alternative site. We examined the effect of stalk mutations on human TfR shedding in transfected CHO cells. Point mutations at R100 led to an increase in alternative shedding while the R100 cleavage product was undetectable. Replacing the TfR‐stalk by the corresponding sequences from tumor necrosis factor‐α or interleukin‐6 receptor also led to TfR ectodomain shedding. These results show that cleavage at alternative sites can compensate for suppressed cleavage at the major site and inhibitor studies reveal that at least three metalloproteases are involved in the shedding process.
Effect of classic preconditioning on the gene expression pattern of rat hearts: a DNA microarray study
Authors: Ónody Annamária , Zvara Ágnes , Hackler László , Vı́gh László , Ferdinandy Péter , G. Puskás László
Published: March 2003

To profile gene expression patterns involved in ischemic preconditioning, we monitored global gene expression changes by DNA microarray analysis of 3200 rat‐specific genes and by real‐time quantitative polymerase chain reaction in rat hearts. Forty‐nine genes with altered expression were found after ischemia/reperfusion as compared to control non‐ischemic hearts and 31 genes were characteristic for classic preconditioning followed by ischemia/reperfusion as compared to ischemia/reperfusion without preconditioning. Genes with altered expression due to ischemia and/or preconditioning included those controlling protein degradation, stress responses, apoptosis, metabolic enzymes, regulatory proteins, and several unknown cellular functions. Metallothionein, natriuretic peptides, coagulation factor VII, cysteine proteinase inhibitor, peroxisome proliferator activator receptor γ and myosin light chain kinase genes were previously suspected to be related to several cardiovascular diseases, however, most of these genes have not previously been shown to be related to myocardial ischemia/reperfusion. Some genes were observed to change specifically in response to preconditioning: oligoadenylate synthase, chaperonin subunit ϵ, a cGMP phosphodiesterase (PDE9A1), a secretory carrier membrane protein, an amino acid transporter, and protease 28 subunit. None of these genes has previously been shown to be involved in the mechanism of preconditioning.
Highly efficient transport of carboxyfluorescein diacetate succinimidyl ester into COS7 cells using human papillomavirus‐like particles
Authors: Bergsdorf Christian , Beyer Carsten , Umansky Viktor , Werr Margaret , Sapp Martin
Published: March 2003

Human papillomavirus virus‐like particles (VLPs) have recently been used to deliver genes into mammalian cells in vitro and in vivo. Here, we investigated whether VLPs may serve as an efficient carrier of low molecular weight compounds (e.g. hormones, vitamins, peptides etc.) into cells. COS7 cells were incubated with recombinant HPV‐16L1/L2 VLPs labelled with the fluorescence dye carboxyfluorescein diacetate succinimidyl ester. Using flow cytometry, we demonstrate that labelled VLPs can specifically bind to the cell surface followed by their complete internalisation. Our results indicate that VLPs are promising vehicles for highly efficient delivery of low molecular weight compounds into cells.
A modified sensor chip for surface plasmon resonance enables a rapid determination of sequence specificity of DNA‐binding proteins
Authors: Hao Dongyun , Ohme-Takagi Masaru , Yamasaki Kazuhiko
Published: March 2003

A novel method is described which rapidly determines specificity of DNA‐binding proteins using a surface plasmon resonance (SPR) sensor chip. An oligohistidine‐tagged DNA‐binding domain of a transcription factor, NtERF2, was immobilised via nitrilotriacetic acid ligands to a sensor chip with an attenuated degree of carboxymethylation. DNA molecules were selected from a pool of randomised oligomers through binding to the immobilised protein and amplified by PCR. After several cycles of selection, during which binding was monitored by SPR, DNA sequences containing a consensus sequence were determined. The time necessary for one cycle is ∼50 min, which is shorter than existing methods.
Na+,K+‐ATPase trafficking in skeletal muscle: insulin stimulates translocation of both α1‐ and α2‐subunit isoforms
Authors: Al-Khalili Lubna , Yu Mei , Chibalin Alexander V
Published: March 2003

We determined insulin‐stimulated Na+,K+‐ATPase isoform‐specific translocation to the skeletal muscle plasma membrane. When rat muscle plasma membrane fractions were isolated by discontinuous sucrose gradients, insulin‐stimulated translocation of α2‐ but not α1‐subunits was detected. However, using cell surface biotinylation techniques, an insulin‐induced membrane translocation of both α1 and α2‐subunits in rat epitrochlearis muscle and cultured human skeletal muscle cells was noted. Na+,K+‐ATPase α‐subunit translocation was abolished by the phosphatidylinositol (PI) 3‐kinase inhibitor wortmannin, as well as by the protein kinase C inhibitor GF109203X. Thus, insulin mediates Na+,K+‐ATPase α1‐ and α2‐subunit translocation to the skeletal muscle plasma membrane via a PI 3‐kinase‐dependent mechanism.
A morphologic study of filamentous phage infection of Escherichia coli using biotinylated phages
Authors: Nakamura Michihiro , Tsumoto Kouhei , Kumagai Izumi , Ishimura Kazunori
Published: March 2003

Using biotinylated phage (BIO‐phages), we observed the infection of filamentous phages into Escherichia coli JM109 morphologically. BIO‐phages and BIO‐phage‐derived proteins, mainly pVIII, were detected in E. coli by using the avidin–biotin–peroxidase complex method with electron microscopy. Infected cells revealed positive staining on the outer and inner membranes and in the periplasmic space. Some cells showed specific or predominant staining of the outer membrane, whereas others showed predominant staining of the inner membrane or equivalent staining of the outer and inner membranes. The periplasmic spaces in some infected cells were expanded and filled with reaction products. Some cells showed wavy lines of positive staining in the periplasmic space. BIO‐phages were detected as thick filaments or clusters covered with reaction products. The ends of the infecting phages were located on the surface of cells, in the periplasmic space, or on the inner membrane. These findings suggest that phage major coat proteins are integrated into the outer membrane and that phages cause periplasmic expansion during infection.
Activation of NF‐κB transcription factor in human neutrophils by sulphatides and L‐selectin cross‐linking
Authors: Turutin Denis V. , Kubareva Elena A. , Pushkareva Marina A. , Ullrich Volker , Sud'ina Galina F.
Published: March 2003

Sulphated galactocerebroside (sulphatide) has been established as a ligand for L‐selectin and shown to trigger intracellular signals in human neutrophils. We have found that sulphatide activated transcription factor NF‐κB in human neutrophils in a concentration‐dependent manner whereas non‐sulphated galactocerebroside did not demonstrate such an effect. The activation was inhibitable by pretreatment with primary monoclonal anti‐L‐selectin antibody (clone LAM1‐116). Binding of the primary antibody to L‐selectin was insufficient to induce NF‐κB activation but cross‐linking of L‐selectin with a secondary antibody was effective. α‐Chymotrypsin, the agent known to shed L‐selectin, activated NF‐κB by itself. The response to sulphatides was inhibited by jasplakinolide, an actin‐polymerising agent known to downregulate surface expression of L‐selectin, FcγRIIIb, CD43 and CD44. Recently we have reported that sulphatide stimulated the attachment of human neutrophils to collagen via Mac1 (CD11b/CD18) integrin [Sud'ina et al., Biochem. J. 359 (2001) 621–629]. We now show signalling from sulphatide to NF‐κB activation and discuss its involvement in neutrophil adhesion.
Survey research in operations management: historical analyses
Authors: Rungtusanatham M.Johnny , Choi Thomas Y , Hollingworth David G , Wu Zhaohui , Forza Cipriano
Published: March 2003

Our paper provides a comprehensive assessment of 285 survey research articles in operations management (OM), published between 1980 and 2000. Six OM journals are included in this study; they are, in alphabetical order: Decision Sciences (DS), International Journal of Operations & Production Management (IJOPM), International Journal of Production Research (IJPR), Journal of Operations Management (JOM), Management Science (MS), and Production and Operations Management (POM). In this paper, we reflect upon the state and evolution of survey research in the OM discipline across a 21‐year time span and the contribution of OM journals that have published these studies. Major changes have occurred in the last 5 years of our sampling period, and two topics stood out as showing fastest ascendancy to prominence—operations strategy and supply chain management. Furthermore, over the years, the Journal of Operations Management appears to have been publishing more survey research articles and a greater variety of OM topics compared to the other five journals in our study.
Adenovirus‐mediated gene transfer to healing tendon—enhanced efficiency using a gelatin sponge
Authors: Dai Quan , Manfield Laura , Wang Yao , Murrell George A. C.
Published: March 2003

Adenovirus‐mediated gene transfer is a potential method for enhancing tendon healing. We investigated the transfection of Ad5CMVntLacZ, an adenovirus containing the reporter gene LacZ, in primary cultured human rotator cuff tendon cells and in a rat Achilles tendon healing model in vivo. Ad5CMVempty, the adenoviral vector containing no inserted gene, was used as a control for adenoviral transfection alone. Activity of β‐galactosidase, the protein expressed by LacZ gene, was measured using a β‐galactosidase assay and detected visually by X‐gal staining. Cultured cells were successfully transfected without impairing cell viability. Maximal β‐galactosidase activity was detected when cells were transfected at the dose of 1000 PFU/cell. The duration of LacZ expression was six days with a peak value at 24 h post‐transfection. A transfection rate of 100% was obtained at 5000 PFU/cell. Successful in vivo transfection by Ad5CMVntLacZ was obtained in healing rat Achilles tendon as confirmed by X‐gal staining. 0.4% of tendon cells were transfected when Ad5CMVntLacZ was injected into the tendon at a dose of 106 PFU. The rate rose to 2% with 108 PFU and 3% with 109 PFU. The duration of LacZ expression in vivo was 17 days. Transfection efficiency was enhanced threefold and localization improved when a gelatin sponge was used to deliver the adenovirus. The results demonstrate that adenovirus can be used to deliver a gene of interest to cultured human rotator cuff tendon cells and healing tendon, with gelatin sponge implantation enhancing adenoviral transfection efficiency in vivo. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Modulation of adhesion, spreading and cytoskeleton organization of 3T3 fibroblasts by sulfonic groups present on polymer surfaces
Authors: Kowalczyńska Hanna M. , Nowak‐Wyrzykowska Małgorzata
Published: March 2003

The early phase of 3T3 fibroblast interaction with sulfonated styrene copolymer surfaces, of two sulfonic group densities and thus of differing wettability, was studied. The sulfonic groups present on copolymer surfaces affected the behaviour of cells, i.e. they stimulated cell adhesion, activated cell spreading and influenced cytoskeleton reorganization. The relative number of adhering cells correlated, while the number of spreading cells inversely correlated, with the surface density of sulfonic groups. Cell shape and the pattern of distribution of F‐actin, α‐actinin and vinculin in the interacting cells also depend on the surface density of sulfonic groups. On surfaces of high sulfonic group density, highly polarized cells were observed with F‐actin bundles. On surfaces of low sulfonic group density, the cells spread with a square‐like morphology with F‐actin organized in stress fibres. In contrast, the cells spread poorly on nonsulfonated surfaces and cell adhesion was unaffected by surface wettability. The contribution of α5β1, α4, and β5integrins to the cell interaction with fibronectin (FN) and vitronectin (VN) adsorbed from serum‐containing medium on polymer surfaces was examined. Our results suggest that surface sulfonic groups influence the conformation of FN and VN adsorbed on polymer surfaces and, in turn, determine the integrins that are involved in cell adhesion.
Endothelial dysfunction and infarct‐size relate to impaired EDHF response in rat experimental chronic heart failure
Authors: Gschwend Simone , Buikema Hendrik , Henning Robert H. , Pinto Yigal M. , de Zeeuw Dick , van Gilst Wiek H.
Published: March 2003

Background:

The rat coronary ligation model of chronic heart failure has been extensively used to investigate its pathophysiology including the role of endothelial dysfunction. Inconsistent results have been obtained concerning the role of endothelial dilative mediators nitric oxide (NO) and endothelium‐derived hyperpolarizing factor (EDHF).

Aims:

Our aim was to investigate involvement of NO and EDHF in aortic endothelial dysfunction in this model and the influence of individual infarct sizes. Furthermore, we investigated whether it is justified to regard rats that failed to develop large infarct sizes as SHAM controls.

Methods:

We performed coronary ligations and SHAM operations and studied acetylcholine (ACh)‐induced relaxations and underlying endothelial mediators in isolated aortic rings 12 weeks after infarction. By then, cardiac and hemodynamic parameters were deteriorated in animals with large myocardial infarctions (large‐MI, 35±3%), but not those with small myocardial infarctions (small‐MI, 5±2%).

Results:

Large‐MI showed decreased ACh‐induced relaxation compared to SHAM due to decreased contribution of EDHF which was inversely correlated with individual infarct‐size. Interestingly, small‐MI showed significantly increased ACh‐induced relaxation compared to SHAM due to increased NO contribution.

Conclusions:

Our results suggest that impaired aortic endothelial dilatory function in large‐MI is mainly due to an impaired EDHF response and strongly depends on individual infarct‐size. In addition, endothelium‐dependent relaxation of small‐MI rats differed from SHAM, indicating that both groups may not be pooled to serve as controls. These results emphasize the importance of infarct‐size and choice of the control group, and may explain inconsistencies in previous studies.
Cerebral blood flow and oxygenation in liver transplantation for acute or chronic hepatic disease without venovenous bypass
Authors: Pere Pertti , Höckerstedt Krister , Isoniemi Helena , Lindgren Leena
Published: March 2003

The autoregulation of cerebral blood flow (CBF) is impaired in patients with end-stage liver disease and encephalopathy. These patients are vulnerable to sudden deterioration of cerebral perfusion and oxygenation during liver transplantation. We compared CBF and metabolism during liver transplantation without venovenous bypass and 24 hours postoperatively in 9 patients with acute liver failure (ALF) and 16 patients with chronic liver disease. A fiberoptic catheter was inserted cranially through the left internal jugular vein for determination of jugular venous oxygen saturation, cerebral oxygen extraction ratio (COER), lactate level, and neuron-specific enolase (NSE) level. Arterial concentrations of lactate were also measured. Flow velocity in the middle cerebral arteries was monitored bilaterally using transcranial Doppler sonography. Mean flow velocity and pulsatility index (PI) were regarded as indicators of intracranial pressure. Core body temperatures were recorded. Mild hyperventilation, perioperative hemofiltration, and N-acetylcysteine infusion were used according to our clinical practice. NSE level was greater in acute patients at the end of surgery (P < .05), but not 24 hours later. Lactate concentrations were greater in patients with ALF (P < .001) preoperatively and intraoperatively but were similar in both groups 24 hours postoperatively. There was no difference between arterial and jugular venous concentrations of lactate. Changes in blood flow velocity, PI, and COER were parallel and without statistical significance between the groups. The patients’ core temperature did not correlate with CBF, NSE level, or clinical outcome. Caval clamping was well tolerated in both patient groups.
Combination low-dose hepatitis B immune globulin and lamivudine therapy provides effective prophylaxis against posttransplantation hepatitis B
Authors: Angus Peter W. , McCaughan Geoffrey W. , Gane Edward J. , Crawford Darryl H.G. , Harley Hugh
Published: March 2003

Although antiviral prophylaxis with lamivudine monotherapy appears to reduce post-liver transplantation recurrence of hepatitis B virus (HBV) infection, breakthrough infections occur in at least 20% of the patients because of the development of drug resistance. Combined lamivudine and intravenous hepatitis B immune globulin (HBIG) therapy (10,000-IU doses) may reduce this risk, but its use is limited by cost (˜US $45,000/yr) and availability. We report the experience at liver transplant centers in Australia and New Zealand in which lamivudine has been used in combination with much lower doses of HBIG than used in conventional HBIG prophylaxis. Lamivudine, 100 mg/d, was administered to hepatitis B surface antigen (HBsAg)-positive candidates on listing for transplantation and was continued posttransplantation. HBIG, 400 or 800 IU, was administered intramuscularly (IM) daily for 1 week from transplantation and monthly thereafter. Thirty-seven HBsAg-positive patients underwent transplantation using this protocol. Thirty-six of these patients were HBV DNA positive by polymerase chain reaction (PCR) or hybridization assay. Thirty-four patients had chronic HBV, 2 patients had hepatitis B and C, and 1 patient had hepatitis B, C, and D. Five patients died within 1 month of transplantation and are not included in the analysis. Mean follow-up in the remaining 32 patients was 18.4 months (range, 5 to 45 months). Treatment was well tolerated, with no significant adverse events. Thirty-one of 32 patients were HBsAg negative, and all 32 patients were HBV DNA negative by PCR at latest follow-up. The cost of treatment was US $967 for lamivudine and between $2,290 and $4,480/yr for IM HBIG. Lamivudine and low-dose HBIG treatment prevents posttransplantation recurrence of hepatitis B and is likely to be more cost-effective than high-dose HBIG regimens.
Vaccination against hepatitis B virus in cirrhotic patients on liver transplant waiting list
Authors: Domínguez Mercedes , Bárcena Rafael , García Miguel , López-Sanroman Antonio , Nuño Javier
Published: March 2003

Patients with cirrhosis may fail to respond to anti-hepatitis B vaccine. An adequate response would be especially interesting when patients are on a liver transplant waiting list. Posttransplantation de novo hepatitis B has been well documented. One possible source is the grafting of organs from hepatitis B surface antigen (HBsAg)-negative, antibody to HBsAg (anti-HBs)-positive, antibody to hepatitis B core antigen-positive donors. The achievement of high titers of anti-HBs could be protective in this setting. We studied prospectively the response rate to recombinant hepatitis B vaccine (3 40-μg doses administered at 0, 1, and 2 months) in 62 patients with end-stage liver disease awaiting liver transplantation. Twenty-two patients showed antibody response (44%). A further 3 doses were administered in 15 of 28 nonresponders and were effective in 9 patients. Thus, the response rate reached 62% (31 of 50 patients completing 1 or 2 vaccination schedules before liver transplantation). Classic hepatitis B vaccination studies of patients with cirrhosis yield lower response rates. Vaccination with this double-dose schedule should be considered in such patients before liver transplantation.
Regulation of PRAK Subcellular Location by p38 MAP Kinases
Authors: New Liguo , Jiang Yong , Han Jiahuai
Published: March 2003

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cellular responses to inflammatory stimuli and environmental stress. p38 regulated/activated protein kinase (PRAK, also known as mitogen-activated protein kinase activated protein kinase 5 [MAPKAPK5]) functions downstream of p38α and p38β in mediating the signaling of the p38 pathway. Immunostaining revealed that endogenous PRAK was predominantly localized in the cytoplasm. Interestingly, ectopically expressed PRAK was localized in the nucleus and can be redistributed by coexpression of p38α or p38β to the locations of p38α and p38β. Mutations in the docking groove on p38α/p38β, or the p38-docking site in PRAK, disrupted the PRAK-p38 interaction and impaired the ability of p38α and p38β to redistribute ectopically expressed PRAK, indicating that the location of PRAK could be controlled by its docking interaction with p38α and p38β. Although the majority of PRAK molecules were detected in the cytoplasm, PRAK is consistently shuttling between the cytoplasm and the nucleus. A sequence analysis of PRAK shows that PRAK contains both a putative nuclear export sequence (NES) and a nuclear localization sequence (NLS). The shuttling of PRAK requires NES and NLS motifs in PRAK and can be regulated through cellular activation induced by stress stimuli. The nuclear content of PRAK was reduced after stimulation, which resulted from a decrease in the nuclear import of PRAK and an increase in the nuclear export of PRAK. The nuclear import of PRAK is independent from p38 activation, but the nuclear export requires p38-mediated phosphorylation of PRAK. Thus, the subcellular distribution of PRAK is determined by multiple factors including its own NES and NLS, docking interactions between PRAK and docking proteins, phosphorylation of PRAK, and cellular activation status. The p38 MAPKs not only regulate PRAK activity and PRAK activation-related translocation, but also dock PRAK to selected subcellular locations in resting cells.
Single-crystal X-ray diffraction and electron-microscopy study of multiple-twinned Sr3(Ru0.336,Pt0.664)CuO6
Authors: Friese Karen , Kienle Lorenz , Duppel Viola , Luo Hongmei , Lin Chengtian
Published: March 2003

Sr_3(Ru_{0.336},Pt_{0.664})CuO_6 crystallizes as a monoclinic structure [space group R12/c; lattice parameters a = 9.595 (15), b = 9.595 (15), c = 11.193 (2) Å and \gamma = 120°]. The crystal structure is pseudotrigonal and the crystal investigated here by single-crystal X-ray diffraction was a multiple twin composed of six individuals. The twin laws are a combination of rhombohedral obverse/reverse twinning plus the threefold axis from the trigonal system. The crystal structure is related to the hexagonal perovskites. Each Pt/Ru atom is coordinated pseudo-octahedrally by O atoms, while the overall coordination polyhedra for Cu atoms can be regarded as a strongly distorted trigonal prism, where the Cu atom is clearly shifted from the center. Each [(Ru_{0.336},Pt_{0.664})O_6] octahedron is connected to two Cu—O polyhedra via a common edge, and thus chains are formed parallel to the crystallographic c axis. Sr^{2+} ions are incorporated between the chains and are coordinated by eight O atoms. All bond distances and angles are in good agreement with literature values. Electron-microscopy studies confirm the results from X-ray diffraction and all observed domain structures can be interpreted exactly with the established twin model. No indication of Pt/Ru ordering was found in either the X-ray or the electron-microscopy investigation.
Experimental charge density in the transition metal complex Mn2(CO)10: a comparative study
Authors: Farrugia Louis J. , Mallinson Paul R. , Stewart Brian
Published: March 2003

An accurate experimental charge density study at 100 K of Mn2(CO)10 [bis(pentacarbonylmanganese)(Mn—Mn)] has been undertaken. A comparison with previously reported structural determinations reveals no evidence for significant Mn—Mn bond lengthening between 100 and 296 K. The nature of the metal–metal and metal–ligand atom interactions has been studied by topological analysis using the Atoms in Molecules (AIM) approach of Bader [(1990), Atoms in Molecules: a Quantum Theory.Oxford: Clarendon Press]. An analysis of the density ρ(r), the Laplacian of the density ∇2ρ(r

b
) and the total energy densities H(r

b
) at the bond critical points is used to classify all the chemical bonds as covalent in nature. The results are compared qualitatively and quantitatively with previous charge density studies on this molecule and DFT calculations at the 6-311+G* B3LYP level. The topological properties of the theoretical and experimental densities are in close agreement.
The 1:1 adduct of triphenylsilanol and 4,4′-bipyridyl, and three pairwise-concomitant triclinic polymorphs of the 4:1 adduct having Z′ = 0.5, 1 and 4
Authors: Bowes Katharine F. , Ferguson George , Lough Alan J. , Glidewell Christopher
Published: March 2003

Crystallization from methanol solution of mixtures of triphenylsilanol and 4,4′-bipyridyl has given a 1:1 adduct (I), Ph3SiOH·C10H8N2, and three polymorphic 4:1 adducts (II)–(IV), (Ph3SiOH)4·C10H8N2. In (I), the components are linked by a single O—H...N hydrogen bond and by a number of C—H...π(arene) hydrogen bonds to form a continuous three-dimensional structure. Compounds (II)–(IV) are all triclinic, space group P\bar 1, with Z′ values of 0.5, 1 and 4, respectively. The basic hydrogen-bonded aggregate is the same in each of (II)–(IV), having a pair of silanol molecules linked to the bipyridyl via O—N...N hydrogen bonds and a further pair of silanol molecules linked to the first pair via O—H...O hydrogen bonds. In (II) there is just one such aggregate lying across a centre of inversion (Z′ = 0.5) and in (III) there are two such aggregates, both lying across centres of inversion (Z′ = 2 × 0.5 = 1). In (IV) there are six independent aggregates of this type, four of which lie across centres of inversion and two of which lie in general positions, so that Z′ = (4 × 0.5) + 2 = 4. While the components in (I) are fully ordered, each of (II)–(IV) exhibits extensive disorder involving both the bipyridyl units and the phenyl rings of the silanol components.
Synthesis and Conformational Analysis of Disubstituted Sparteine Derivatives
Authors: Boczoń Władysław , Jasiewicz Beata
Published: March 2003

Synthesis of disubstituted sparteine derivatives and their diperchlorate salts was performed. Their IR and NMR spectra were analysed to determine the structure of these compounds, as well as the substituent and the protonation effects. It was shown that both unsaturated (2,17β-dimethyl-2,3-didehydrosparteine (12), 17β-isopropyl-2-methyl-2,3-didehydrosparteine (13)) and saturated (2,17β-dimethylsparteine (14), 17β-isopropyl-2-methylsparteine (15)) newly obtained sparteine derivatives have the same configurational-conformational system: trans A/B chair/chair, trans C/D boat/chair. The methyl and the isopropyl (both equatorial) groups at C-17 appear the elements stabilizing the boat-chair system of the C/D rings, which does not change either on the introduction of the second substituent to the opposite quinolizidine system (the A/B rings) or on protonation. The protonation of the free bases obtained gives only disalts. The atoms undergoing the protonation are either C-3 and N-16 in 12 and 13 or both nitrogen atoms (N-1 and N-16) in 14 and 15. The methyl group introduced on the carbon atom C-2 takes equatorial position, as in 2-methylsparteine (2).
PION DEUTERON SCATTERING LENGTH IN EFFECTIVE FIELD THEORY
Authors: BORASOY BUGRA , GRIEßHAMMER HARALD W.
Published: March 2003

The S wave pion deuteron scattering length is presented in an effective field theory approach of the two-nucleon system. We include pions as dynamical particles which allows us to calculate pion re-scattering contributions inside the deuteron. Two-nucleon two-pion contact interactions with unknown parameters not determined by chiral symmetry need to be introduced in order to renormalise the appearing divergences. By choosing their values accordingly we are able to accommodate the available experimental data.
DIETARY, EVOLUTIONARY, ANDMODERNIZINGINFLUENCES ON THEPREVALENCE OFTYPE2 DIABETES
Authors: Lieberman Leslie Sue
Published: March 2003

▪ Abstract  An evolutionary perspective is used to elucidate the etiology of the current epidemic of type 2 diabetes estimated at 151 million people. Our primate legacy, fossil hominid, and hunting-gathering lifestyles selected for adaptive metabolically thrifty genotypes and phenotypes are rendered deleterious through modern lifestyles that increase energy input and reduce output. The processes of modernization or globalization include the availability and abundance of calorically dense/low-fiber/high-glycemic foods and the adoption of sedentary Western lifestyles, leading to obesity among both children and adults in developed and developing countries. These trends are projected to continue for a number of decades.
NUTRITION IN THEPERIOPERATIVEPATIENT
Authors: Howard Lyn , Ashley Christopher
Published: March 2003

▪ Abstract  The association of malnutrition with surgical morbidity and mortality is well recognized. The question of whether this relationship is causal or simply an association in sick patients has been hotly debated. The field of nutrition support has grown out of the belief that correcting malnutrition will modify associated risks for poor outcome. It has been easier to substantiate this belief in some clinical situations than in others. The evidence for nutrition support during the perioperative period is reviewed and recommendations are made about where nutrition support is most useful and where it may be counterproductive. Some of the important unanswered questions about perioperative nutrition support are raised.
Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum
Authors: Omodeo-Salè Fausta , Motti Anna , Basilico Nicoletta , Parapini Silvia , Olliaro Piero , Taramelli Donatella
Published: March 2003

Red blood cells infected withPlasmodium falciparum(IRBCs) undergo changes primarily in their membrane composition that contribute to malaria pathogenesis. However, all manifestations (eg, anemia) cannot be accounted for by IRBCs alone. Uninfected erythrocytes (URBCs) may play a role, but they have been under-researched. We wanted to document changes in the erythrocyte membrane that could contribute to URBC reduced life span and malaria-associated anemia. Human erythrocytes were cultured withP falciparumand washed at the trophozoite stage. IRBCs and URBCs were separated on Percoll density gradient, thus obtaining erythrocyte fractions of different densities/ages. IRBC- and URBC-purified membranes were analyzed and compared with control normal erythrocytes (NRBCs) of the same age, from the same donor, kept in the same conditions.P falciparumaccelerated aging of both IRBCs and URBCs, causing a significant shift in the cell population toward the denser (old) fraction. Protein, phospholipid, and cholesterol content were reduced in IRBCs and young URBCs. Young and medium uninfected fractions had higher levels of lipid peroxidation and phospholipid saturation (because of the loss of polyunsaturated fatty acids, PUFAs) and lower phosphatidylserine. In IRBCs, thiobarbituric reactive substances (TBARSs) were higher, and PUFAs and phosphatidylserine lower than in NRBCs and URBCs. In comparison, trophozoite membranes had lower phospholipid (particularly sphingomyelin and phosphatidylserine) and cholesterol content and a higher degree of saturation. Parasite-induced peroxidative damage might account for these modifications. In summary, we demonstrated that membrane damage leading to accelerated senescence of both infected and uninfected erythrocytes will likely contribute to malaria anemia.
Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features
Authors: de Jong Daphne , Glas Annuska M. , Boerrigter Lucie , Hermus Marie-Christine , Dalesio Otilia , Willemse Els , Nederlof Petra M. , Kersten Marie José
Published: March 2003

Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic background? In 10 of 13 DLBCL patients with relapse after 4 to 17 years, a clonal relationship was established based on identical IgH-sequences and/or identical bcl2-IgH translocation. Most (77%) showed features of germinal center (GC) cells, as defined by expression of CD10, bcl-2, and bcl-6 protein and ongoing immunoglobulin heavy chain variable region (VH) hypermutation. A GC phenotype was seen in 8 (20%) of 38 control patients matched for age, stage, and (extra)nodal localization with relapse within 2.5 years (P = .005). In conclusion, we have found evidence that late-relapsing DLBCL represents truly clonally related disease episodes in most cases and that this clinical behavior may be related to the biologic features of GC cells. (Blood. 2003;102:324-327)
SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes
Authors: Giles Francis J. , Stopeck Alison T. , Silverman Lewis R. , Lancet Jeffrey E. , Cooper Maureen A. , Hannah Alison L. , Cherrington Julie M. , O'Farrell Anne-Marie , Yuen Helene A. , Louie Sharianne G. , Hong Weiru , Cortes Jorge E. , Verstovsek Srdan , Albitar Maher , O'Brien Susan M. , Kantarjian Hagop M. , Karp Judith E.
Published: March 2003

Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are adverse prognostic features in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDSs). VEGF is a soluble circulating angiogenic molecule that stimulates signaling via receptor tyrosine kinases (RTKs), including VEGF receptor 2 (VEGFR-2). AML blasts may express VEGFR-2, c-kit, and FLT3. SU5416 is a small molecule RTK inhibitor (RTKI) of VEGFR-2, c-kit, and both wild-type and mutant FLT3. A multicenter phase 2 study of SU5416 was conducted in patients with refractory AML or MDS. For a median of 9 weeks (range, 1-55 weeks), 55 patients (33 AML: 10 [30%] primary refractory, 23 [70%] relapsed; 22 MDS: 15 [68%] relapsed) received 145 mg/m2 SU5416 twice weekly intravenously. Grade 3 or 4 drug-related toxicities included headaches (14%), infusion-related reactions (11%), dyspnea (14%), fatigue (7%), thrombotic episodes (7%), bone pain (5%), and gastrointestinal disturbance (4%). There were 11 patients (20%) who did not complete 4 weeks of therapy (10 progressive disease, 1 adverse event); 3 patients (5%) who achieved partial responses; and 1 (2%) who achieved hematologic improvement. Single agent SU5416 had biologic and modest clinical activity in refractory AML/MDS. Overall median survival was 12 weeks in AML patients (range, 4-41 weeks) and not reached in MDS patients. Most observed toxicities were attributable to drug formulation (polyoxyl 35 castor oil or hyperosmolarity of the SU5416 preparation). Studies of other RTKI and/or other antiangiogenic approaches, with correlative studies to examine biologic effects, may be warranted in patients with AML/MDS.
CD8α+ mouse spleen dendritic cells do not originate from the CD8α- dendritic cell subset
Authors: Naik Shalin , Vremec David , Wu Li , O'Keeffe Meredith , Shortman Ken
Published: March 2003

Although previous studies had indicated that the CD8α- and CD8α+ subtypes of murine dendritic cells (DCs) differ in immediate origin, a recent study found that intravenous transfer of CD8α- DCs led to CD8α+ DCs in the spleen several days later, suggesting a direct precursor-product relationship. We have repeated these experiments with a balance sheet approach. We find that though a few CD8α+ DCs can be generated in such experiments, this is a rare event and could be the result of a contaminant precursor. Most of the immediate precursors of CD8α+ DCs are cells that lack the phenotype of a recognizable DC. CD8α- DCs and CD8α+ DCs are not precursor-product related, though these sublineages may be connected further upstream.
Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)–deficient mice
Authors: Dziarski Roman , Platt Kenneth A. , Gelius Eva , Steiner Håkan , Gupta Dipika
Published: March 2003

Insect peptidoglycan recognition protein-S (PGRP-S), a member of a family of innate immunity pattern recognition molecules conserved from insects to mammals, recognizes bacterial cell wall peptidoglycan and activates 2 antimicrobial defense systems, prophenoloxidase cascade and antimicrobial peptides through Toll receptor. We show that mouse PGRP-S is present in neutrophil tertiary granules and that PGRP-S–deficient (PGRP-S-/-) mice have increased susceptibility to intraperitoneal infection with gram-positive bacteria of low pathogenicity but not with more pathogenic gram-positive or gram-negative bacteria. PGRP-S-/- mice have normal inflammatory responses and production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Neutrophils from PGRP-S-/- mice have normal phagocytic uptake of bacteria but are defective in intracellular killing and digestion of relatively nonpathogenic gram-positive bacteria. Therefore, mammalian PGRP-S functions in intracellular killing of bacteria. Thus, only bacterial recognition by PGRP-S, but not its effector function, is conserved from insects to mammals.
PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis
Authors: Gao Cunji , Sun Weiyong , Christofidou-Solomidou Melpo , Sawada Motoshi , Newman Debra K. , Bergom Carmen , Albelda Steven M. , Matsuyama Shigemi , Newman Peter J.
Published: March 2003

Programmed cell death, or apoptosis, is a tightly regulated, naturally occurring process by which damaged or unwanted cells are removed. Dysregulated apoptosis has been implicated in a variety of pathophysiological conditions, including degenerative diseases, tissue remodeling, and tumorogenesis. The decision to live or die results from integration of numerous environmental signals transmitted by specific classes of cell surface receptors that bind hormones, growth factors, or components of the extracellular matrix. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM-1), a homophilic-binding member of the immunoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, functions prominently to inhibit apoptosis in naturally occurring vascular cells subjected to apoptotic stimuli. Murine endothelial cells and human T lymphocytes lacking PECAM-1 were found to be far more sensitive than their PECAM-1—expressing counterparts to multiple death signals that stimulate Bax, a multidomain, proapoptotic member of the Bcl-2 family that plays a central role in mitochondrial dysfunction-dependent apoptosis. In addition, PECAM-1 markedly suppressed Bax overexpression—induced cytochrome c release, caspase activation, and nuclear fragmentation. Amino acid substitutions within PECAM-1's extracellular homophilic binding domain, or within its cytoplasmic ITIM, completely abolished PECAM-1—mediated cytoprotection. Taken together, these data implicate PECAM-1 as a novel and potent suppressor of Bax-mediated apoptosis and suggest that members of the immunoglobulin gene (Ig) superfamily, like cell surface integrins, may also transmit survival signals into blood and vascular cells. (Blood. 2003;102:169-179)
Adaptive control using multiple models, switching and tuning
Authors: Narendra Kumpati S. , Driollet Osvaldo A. , Feiler Matthias , George Koshy
Published: March 2003

The past decade has witnessed a great deal of interest in both the theory and practice of adaptive control using multiple models, switching, and tuning. The general approach was introduced in the early 1990s to cope with large and rapidly varying parameters in control systems. During the following years, detailed mathematical analyses of special classes of systems were carried out. Considerable empirical evidence was also collected to demonstrate the practical viability of the methods proposed. This paper attempts to review critically the stability questions that arise in the study of such systems, describes recent extensions of the approach to non‐linear adaptive control, and discuss briefly promising new areas of research, particularly related to the location of models. Copyright © 2003 John Wiley & Sons, Ltd.