bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of N19S‐SOD1, an SOD1 mutant found in sporadic amyotrophic lateral sclerosis patients, induceslow‐grade motoneuronal toxicity
Authors: Obata Yuji , Niikura Takako , Kanekura Kohsuke , Hashimoto Yuichi , Kawasumi Masaoki , Kita Yoshiko , Aiso Sadakazu , Matsuoka Masaaki , Nishimoto Ikuo
Published: July 2005

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease. It has been generally accepted that the proapoptotic property of the familial ALS (FALS)‐linked mutant SOD1 genes plays an important role in the pathogenesis of some FALS cases. We found here that expression of N19S‐SOD1, a novel SOD1 mutant originally found in a sporadic ALS patient, induces lower grade death in NSC34 cells than FALS‐linked mutant SOD1. In agreement, intracytoplasmic aggregate formation and SOD1 polymerization are less prominently induced by ectopic expression of N19S‐SOD1 than FALS‐linked mutant SOD1. We further found that additional cell stresses, such as inhibition of proteasomal activity or up‐regulation of intracellular oxidative stress, enhance N19S‐SOD1‐induced aggregate formation and polymerization of N19S‐SOD1. Such analysis of the intracellular polymerization and the ubiquitination of N19S‐SOD1 have further suggested that it is recognized as a misfolded protein, like FALS‐linked mutant SOD1, whereas wild‐type SOD1 is not. Altogether, it is speculated that the N19S mutation of SOD1 in cooperation with associated cell stresses contributes to the onset of ALS as a risk factor. © 2005 Wiley‐Liss, Inc.
Expression of the transcription factor Pax6 in the adult rat dentate gyrus
Authors: Nacher Juan , Varea Emilio , Blasco‐Ibañez Jose M. , Castillo‐Gomez Esther , Crespo Carlos , Martinez‐Guijarro Francisco J. , McEwen Bruce S.
Published: July 2005

The transcription factor Pax6 is expressed in precursor cells during embryonic CNS development, and it plays an important role in the regulation of cell proliferation and neuronal fate determination. Pax6‐expressing cells are also present in the adult hippocampal dentate gyrus and subventricular zone/rostral migratory stream, regions in which neuronal precursors exist during adult life. In the adult dentate gyrus, precursor cells are located in the innermost portion of the granule cell layer, and Pax6‐expressing nuclei are most abundant in this region. To examine the putative role of Pax6 in adult hippocampal neurogenesis, we have studied the proliferative activity, distribution, and phenotype of Pax6‐expressing cells by using immunohistochemistry. Our results indicate that Pax6 is intensely expressed in proliferating precursors of the adult dentate gyrus. Pax6 is also expressed in nonproliferating cells, which may correspond to resting progenitor cells and to granule neurons in their very early developmental stages, because this transcription factor is strongly down‐regulated during granule neuron differentiation. However, a small subpopulation of hilar mature neurons and certain astrocytes of the adult hippocampus also express Pax6. Although the precise roles of this transcription factor in the adult brain remain to be determined, our findings support the idea that its function in the control of cell proliferation and neuronal fate determination during embryogenesis is also operative in the adult hippocampus. However, the expression of Pax6 in astrocytes and certain mature neurons may indicate the existence of other roles for this transcription factor in this telencephalic region. © 2005 Wiley‐Liss, Inc.
A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients
Authors: Davis Gary L. , Nelson David R. , Terrault Norah , Pruett Timothy L. , Schiano Thomas D. , Fletcher Courtney V. , Sapan Christine V. , Riser Laura N. , Li Yufeng , Whitley Richard J. , Gnann John W.
Published: July 2005

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients. (Liver Transpl 2005;11:941–949.)
Rapid, large-scale formation of porcine hepatocyte spheroids in a novel spheroid reservoir bioartificial liver
Authors: Nyberg Scott L. , Hardin Joseph , Amiot Bruce , Argikar Upendra A. , Remmel Rory P. , Rinaldo Piero
Published: July 2005

We have developed a novel bioreactor based on the observation that isolated porcine hepatocytes rapidly and spontaneously aggregate into spheroids under oscillation conditions. The purpose of this study was to characterize the influence of oscillation frequency (0.125 Hz, 0.25 Hz), cell density (1-10 × 106 cells/mL), and storage condition (fresh, cryopreserved) of porcine hepatocytes on the kinetics of spheroid formation. The viability and metabolic performance of spheroid hepatocytes was also compared to monolayer culture. We observed that both fresh and cryopreserved porcine hepatocytes began formation of spheroids spontaneously at the onset of oscillation culture. Spheroid size was directly related to cell density and time in culture, though inversely related to oscillatory frequency. Spheroid formation by fresh porcine hepatocytes was associated with decreased cell death (lactate dehydrogenase release, 1.3 ± 1.0 vs. 3.1 ± 0.7 U/mL,

P

< 0.05) and increased metabolic performance (albumin production, 14.7 ± 3.3 vs. 4.6 ± 1.4 fg/c/h,

P

< 0.0001; ureagenesis from ammonia, 267 ± 63 vs. 92 ± 13 μmol/L/h,

P

< 0.001) compared with monolayer culture. In conclusion, based on the favorable properties of rapid spheroid formation, increased hepatocellular function, and ease of scale-up, the spheroid reservoir bioreactor warrants further investigation as a bioartificial liver for support of liver failure. (Liver Transpl 2005;11:901–910.)
Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease
Authors: Planinsic Raymond M. , van der Meer Jan , Testa Giuliano , Grande Luis , Candela Angel , Porte Robert J. , Ghobrial Mark R. , Isoniemi Helena , Schelde Peter Billeskov , Erhardtsen Elisabeth , Klintmalm Goran , Emre Sukru
Published: July 2005

Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 μg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required. (Liver Transpl 2005;11:895–900.)
Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: A prospective single-center study
Authors: Millonig Gunda , Graziadei Ivo W. , Eichler Dagmar , Pfeiffer Karl-Peter , Finkenstedt Gerd , Muehllechner Petra , Koenigsrainer Alfred , Margreiter Raimund , Vogel Wolfgang
Published: July 2005

Bone loss is a common complication in patients before and after liver transplantation (LT). The aim of this study was to investigate the efficacy of prophylactic treatment with bisphosphonates after LT in preventing progressive bone loss in LT patients. We included 136 patients with end-stage liver diseases awaiting LT. Bone mineral density (BMD) (by dual X-ray absorptiometry) and markers of bone metabolism were determined before, and 4, 12, 24, 36, and 48 months after LT. All patients received vitamin D and calcium supplementation before and after LT, those with osteopenia or osteoporosis prior to LT were additionally treated with alendronate following LT. Decreased BMD was seen in a high percentage of patients undergoing LT (osteopenia 48.5%, osteoporosis 23.5%). Reduced BMD before LT was not related to gender, underlying liver disease, or Child-Turcotte-Pugh classification. Body mass index (BMI) prior to LT, however, correlated significantly with the fracture risk. Alendronate prevented the ubiquitously observed bone loss after LT in patients with osteoporosis and osteopenia and, in addition, led to an increase in BMD in patients with osteoporosis within 24 months after LT. In conclusion, our study suggests that alendronate is efficacious in preventing the natural course of bone loss associated with LT. (Liver Transpl 2005;11:960–966.)
Transplantation of hepatitis B surface antigen–positive livers into hepatitis B virus–positive recipients and the role of hepatitis delta coinfection
Authors: Franchello Alessandro , Ghisetti Valeria , Marzano Alfredo , Romagnoli Renato , Salizzoni Mauro
Published: July 2005

The scarcity of liver donors requires consideration of grafts from sources not previously used. Allografts from hepatitis B surface antigen (HBsAg)-carriers without a significant liver disease have been proposed for liver transplant recipients with hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Combination prophylaxis schemes against HBV post-liver transplantation (LT) recurrence are currently available; the efficacy of those schemes in HBV-related cirrhosis and HCC must be assessed. This report describes the allocation of HBsAg-positive grafts in three HBsAg-positive recipients, with HBV-related cirrhosis and evolving HCC lesions, two of them with hepatitis Delta virus (HDV) coinfection. Patients were administered anti-hepatitis B immunoglobulins (HBIGs) and lamivudine in order to prevent HBV recurrence. In spite of anti-HBV prophylaxis, HBV infection did persist after LT in all patients (no serum clearance of HBsAg). HBV replication assessed by serum HBV deoxyribonucleic acid (DNA) presence was detected in the first month after LT in the 3 recipients. A prompt HDV reinfection with a clinical and histological pattern of hepatitis was observed in the 2 HBV / HDV coinfected recipients. In 1 of them, an evolving chronic hepatitis required a second LT. The non-HDV–infected patient showed an uneventful follow-up, but the lack of the neutralizing effect of HBIGs and the high risk of escape mutants forced the addition of adefovir-dipivoxil to lamivudine, in order to prevent viral variants and hepatitis recurrence. In conclusion, allografts from HBsAg-positive donors in HBsAg-positive recipients are associated with the persistence of the HBsAg after LT due to the failure of HBIG prophylaxis, even if lamivudine does inhibit virion production. This condition favors HDV replication and HDV hepatitis recurrence in coinfected patients. The allocation of HBsAg-positive grafts in HBsAg-positive recipients could be justified only in recipients without HDV coinfection and a combined prophylaxis with lamivudine and adefovir-dipivoxil is currently the best way to manage escape mutants in these recipients. (Liver Transpl 2005;11:922–928.)
Whole fetal liver transplantation—A new approach to cell therapy
Authors: Oren Ran , Breitman Yigal , Gur Eyal , Traister Alexandra , Zvibel Isabel , Brazovsky Eli , Shafritz David A. , Halpern Zamir
Published: July 2005

We recently developed a novel rat model for liver repopulation, heterografting of microliver slices, aimed at overcoming the limitations inherent in both whole liver and hepatocyte transplantations. The aim of the present study was to evaluate the potential of whole fetal liver transplantations to survive and differentiate within the adult liver, using the adult liver slice transplantation model. Embryonic day 14 whole fetal livers from dipeptidyl peptidase IV+/+ wild-type Fischer 344 rats were transplanted into the livers of dipeptidyl peptidase IV−/− mutant rats. Adult hepatic markers, dipeptidyl peptidase IV, albumin, glycogen, and proliferation cell nuclear antigen- proliferation cell nuclear antigen (PCNA) were assessed in the transplanted liver tissue by immunohistochemistry. Two groups of 9 rats each were transplanted with 3 fetal livers per recipient. Two months later the rats were sacrificed and the markers were detected in the transplanted tissues. In conclusion, the results of this study raise the possibility that fetal liver transplantation could serve as a model for genetic metabolic liver diseases. (Liver Transpl 2005;11:929–933.)
Generalized, pruritic, ulcerating maculopapular rash necessitating cessation of sirolimus in a liver transplantation patient
Authors: Tracey Christopher , Hawley Carmel , Griffin Anthony Donald , Strutton Geoff , Lynch Stephen
Published: July 2005

The use of sirolimus as an alternative to calcineurin antagonists has enabled the continuation of immunosuppression in patients with renal impairment with preservation of kidney function. Sirolimus is generally well tolerated, with the main causes of cessation of therapy related to its effect on blood lipid profile as well as leukopenia and thrombocytopenia. We report a case of a debilitating ulcerating maculopapular rash necessitating cessation of the drug in a liver transplantation patient. A 56-year-old Caucasian liver transplantation patient presented with a diffuse, debilitating rash attributed to sirolimus use. This ultimately necessitated cessation of the immunosuppressant with subsequent resolution of her symptoms. From a review of the current literature, this is a highly unusual adverse reaction to sirolimus. (Liver Transpl 2005;11:987–989.)
Diarrhea in liver transplant recipients: Etiology and management
Authors: Ginsburg Philip M. , Thuluvath Paul J.
Published: July 2005

Diarrhea is common after liver transplantation (LT). The true incidence of diarrhea in liver transplant recipients is unknown but possibly ranges from 10% to 43% based on a few published studies in other solid organ and bone marrow transplantation. Infectious etiologies, including cytomegalovirus (CMV),

Clostridium difficile

, and occasional atypical intestinal infections, are the most common causes. Diarrhea is also a frequent side effect of immunosuppressive medications. To variable extents, mycophenolate mofetil (MMF), cyclosporine A (CSA), tacrolimus, and sirolimus are all known to be associated with diarrhea. Rarely, graft-versus-host disease (GVHD), lymphoproliferative disorder, de novo inflammatory bowel disease (IBD), or colon cancer may present as diarrhea. Flare-up of preexisting IBD is also not uncommon after LT. However, the cause of acute diarrhea remains unidentified in 1 of 3 patients. This review summarizes the literature and provides recommendations on the management of acute diarrhea after LT. Although our focus is on LT, the etiology and management recommendations apply to most transplant recipients. (Liver Transpl 2005;11:881–890.)
Sequential and simultaneous revascularization in adult orthotopic piggyback liver transplantation
Authors: Polak Wojciech G. , Miyamoto Shungo , Nemes Balazs A. , Peeters Paul M.J.G. , de Jong Koert P. , Porte Robert J. , Slooff Maarten J.H.
Published: July 2005

The aim of the study was to assess whether there is a difference in outcome after sequential or simultaneous revascularization during orthotopic liver transplantation (OLT) in terms of patient and graft survival, mortality, morbidity, and liver function. The study population consisted of 102 adult patients with primary full-size piggyback OLT transplanted between January 1998 and December 2001. In 71 patients (70%) the grafts were sequentially reperfused after completion of the portal vein anastomosis and subsequent arterial reconstruction was performed (sequential reperfusion [SeqR] group). In 31 patients (30%) the graft was reperfused simultaneously via the portal vein and hepatic artery (simultaneous reperfusion [SimR] group). Patient and graft survival at 1, 3, and 6 months and at 1 year did not differ between the SeqR group and the SimR group. The red blood cell (RBC) requirements were significantly higher in the SimR group (5.5 units; range 0-20) in comparison to the SeqR group (2 units; range 0-19) (

P

= 0.02). Apart from a higher number of biliary anastomotic complications and abdominal bleeding complications in the SimR group in comparison to the SeqR group (13% vs. 2% and 19% vs. 6%, respectively;

P

= 0.06), morbidity was not different between the groups. No differences between the groups were observed regarding the incidence of primary nonfunction (PNF), intensive care unit stay, and acute rejection. This was also true for the severity of rejections. Postoperative recuperation of liver function was not different between the groups. In conclusion, no advantage of either of the 2 reperfusion protocols could be observed in this analysis, especially with respect to the incidence of ischemic type biliary lesions (ITBL). (Liver Transpl 2005;11:934–940.)
Stress-inducing factors in ICUs: What liver transplant recipients experience and what caregivers perceive
Authors: Biancofiore Gianni , Bindi Maria L. , Romanelli Anna Maria , Urbani Lucio , Mosca Franco , Filipponi Franco
Published: July 2005

The aim of this study was to compare a number of potentially stress-generating factors related to an intensive care unit (ICU) stay from the points of view of patients undergoing liver transplantation or elective major abdominal surgery and their caregivers in order to identify differences and similarities that may help to optimize patient care. The ICU Environmental Stressor Scale questionnaire was administered to 104 liver transplant recipients, 103 major abdominal surgery patients, 35 nurses and 21 physicians. The ICU staff were asked to complete the questionnaire on the basis of their perception of patient stressors. Both patient groups identified

Being unable to sleep

,

Being in pain

,

Having tubes in nose/mouth

,

Missing husband/wife

, and

Seeing family and friends only a few minutes a day

as the major stressors; the healthcare providers correctly identified the most stressing factors for the patients, but gave them higher scores. The mean scores were 71.9 ± 18.7 for the transplant recipients, 66.3 ± 20.9 for the patients undergoing elective major abdominal surgery, 99.7 ± 19.2 for the nurses, and 92.7 ± 16.1 for the physicians (

P

< 0.001). The qualitative evaluations of potentially stress-inducing ICU situations were substantially the same in the 2 patient groups, but the transplant recipients seemed to feel them more acutely. Although the caregivers identified the most discomforting situations, they overestimated the degree of stress they cause. The staff of each ICU should therefore seek to understand and reduce (even by means of simple interventions) the particular causes of psychophysical stress felt by their patients. (Liver Transpl 2005;11:967–972.)
Crack Toughness Behaviour of Multiwalled Carbon Nanotube (MWNT)/Polycarbonate Nanocomposites
Authors: Satapathy Bhabani K. , Weidisch Roland , Pötschke Petra , Janke Andreas
Published: July 2005

Summary: The morphology and fracture behaviour of polycarbonate (PC)/multiwalled carbon nanotube (MWNT) composites have been studied by AFM and post‐yield fracture mechanics. The essential work of fracture (EWF) method has been used to distinguish between two terms representing the resistance to crack initiation and crack propagation. A maximum in the non‐essential work of fracture was observed at 2 wt.‐% MWNT, demonstrating enhanced resistance to crack propagation compared to pure PC. At 4 wt.‐% MWNT, a tough‐to‐brittle transition has been observed. The time‐resolved in‐situ strain field analysis revealed that the onset of crack initiation was shifted to a shorter time for nanocomposites with 4 wt.‐% MWNT compared to that with 2 wt.‐%, and thus explained the existence of a tough‐to‐brittle transition in these nanocomposites.

magnified image
Synthesis of Polyaniline‐Vanadium Oxide Nanocomposite Nanosheets
Authors: Pang Shuping , Li Guicun , Zhang Zhikun
Published: July 2005

Summary: Polyaniline‐vanadium oxide nanocomposite nanosheets with thickness between 10 and 20 nm, and lateral dimensions in the range of hundreds of nanometers to several microns have been synthesized by in situ intercalation polymerization of aniline with layered V2O5 under hydrothermal conditions. The product was characterized by field‐emission scanning electron microscopy (FE‐SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT‐IR) spectroscopy, and X‐ray diffractometer (XRD). The effects of the concentration of aniline and reaction temperature on the morphologies of polyaniline‐vanadium oxide nanocomposites have also been investigated.

SEM image of tremella‐like polyaniline‐vanadium oxide nanocomposite nanosheets.

magnified image

SEM image of tremella‐like polyaniline‐vanadium oxide nanocomposite nanosheets.
Ambipolar Field‐Effect Transistor (FET) and Redox Characteristics of a π‐Conjugated Thiophene/1,3,4‐Thiadiazole CT‐Type Copolymer
Authors: Yamamoto Takakazu , Yasuda Takuma , Sakai Yoshimasa , Aramaki Shinji
Published: July 2005

Summary: A π‐conjugated charge transfer‐type copolymer consisting of an electron‐donating thiophene and an electron‐accepting 1,3,4‐thiadiazole, P(ThdzTh), underwent facile electrochemical p‐ and n‐doping, as revealed by cyclic voltammetry. The copolymer gave a new ambipolar field‐effect transistor (FET), which showed typical IDS (source–drain current)–VDS (source–drain voltage) curves in both a p‐type working mode and an n‐type working mode. In the n‐type working mode, the polymer showed a carrier mobility of about 5 × 10−3 cm2 · V−1 · s−1 and an on/off ratio of about 3 × 104.

n‐Channel field‐effect transistor characteristics of P(ThdzTh).

magnified image

n‐Channel field‐effect transistor characteristics of P(ThdzTh).
Intra‐abdominal desmoid tumor after successful treatment for Hodgkin disease
Authors: Rosoff Philip M. , Larrier Nicole , Rice Henry E.
Published: July 2005

The risk of second malignancies after successful treatment for Hodgkin disease can be considerable. The most common malignancies are solid tumors arising in irradiated sites, such as the breast and thyroid gland after mantle field radiation. Sarcomas and other musculoskeletal tumors are also seen. We describe a young woman who developed an intra‐abdominal desmoid tumor more than 4 years after completing therapy for Stage IIB Hodgkin disease, treated with combination chemotherapy (ABVD) and mantle irradiation. The tumor did not occur at either a surgical site or within a radiation field. She did not carry a mutation for familial adenomatosis polypoli. © 2005 Wiley‐Liss, Inc.
Treatment of Wilms tumor according to SIOP 9 protocol in Casablanca, Morocco
Authors: Madani Abdellah , Zafad Saadia , Harif M'hamed , Yaakoubi Mohammed , Zamiati Soumaya , Sahraoui Souha , Benjelloun Amal , Fehri Mohammed , Benchekroun Said
Published: July 2005

Background

Childhood Wilms tumor represents one of the challenge for pediatric oncologists in developing countries. We report the characteristics and treatment results of patients with Wilms tumor according to SIOP 9 protocol in Morocco.

Procedure

From January 1989 to December 2000, 86 children with Wilms tumor were admitted. The diagnosis was based on physical exam and abdominal ultrasound. The metastatic work‐up was based on abdominal ultrasound and chest X‐ray.

Results

The mean age was 36 months (3–120 months). The sex‐ratio was 1. Abdominal mass was the main symptom at presentation (84 cases). There were 13 metastatic cases. Treatment applied was according to SIOP 9 Protocol without randomization. Local deases was present in 75 patients with stage I in 38 cases (50%), IIN0 in 4 cases (6%), IIN1 in 9 cases, and III in 24 cases (44%). The distribution of pathologic groups was: favorable in 4 cases, standard in 69 cases, and unfavorable anaplastic type in 2 cases. Sixty‐nine patients were evaluable for therapeutic evaluation. Other patients were lost to follow‐up. Three patients died of treatment related toxicity and 13 patients relapsed. With a median follow‐up of 70 months, the 5‐year EFS and 5 years overall survival for evaluable patients are 77.4% and 79%, respectively while the 5‐year EFS for all patients was 56%.

Conclusion

These results are encouraging for a developing country but special efforts should be done to reduce the rate of abandonment. Pediatr Blood Cancer 2006, 46:472–475. © 2005 Wiley‐Liss, Inc.
Obesity in pediatric oncology
Authors: Rogers Paul C. , Meacham Lillian R. , Oeffinger Kevin C. , Henry David W. , Lange Beverly J.
Published: July 2005

Today's obesity pandemic began in the United States, spread to Western Europe and other developed regions, and is emerging in developing countries. Its influences on outcomes of childhood cancer are unknown. A recent Children's Oncology Group symposium considered epidemiology of obesity, pharmacology of chemotherapy and outcomes in obese adults with cancer, excess mortality in obese pediatric patients with acute myeloid leukemia (AML), and complications in obese survivors. The salient points are summarized herein. Body mass index (BMI) is the accepted index of weight for height and age. In the US, obesity prevalence (BMI > 95th centile) is increasing in all pediatric age groups and accelerating fastest among black and Hispanic adolescents. Pharmacologic investigations are few and limited: half‐life, volume of distribution, and clearance in obese patients vary between drugs. Obese adults with solid tumors generally experience less toxicity, suggesting underdosing. For patients undergoing bone marrow transplantation, obese adults generally experience greater toxicity. In pediatric acute myeloblastic leukemia, obese patients have greater treatment‐related mortality (TRM), similar toxicity and relapse rates, and inferior survival compared with patients who are not obese. An excess of female survivors of childhood leukemia who received cranial irradiation are obese. Ongoing treatment effects of childhood cancer may predispose to a sedentary lifestyle. These findings call for measures to prevent obesity, retrospective and prospective studies of chemotherapy pharmacology of analyzed according to BMI and outcomes, additional studies of the obesity impact on outcomes in pediatric cancer, and promotion of a healthy lifestyle among survivors. © 2005 Wiley‐Liss, Inc.
Osteopenia, physical activity and health‐related quality of life in survivors of brain tumors treated in childhood
Authors: Odame Isaac , Duckworth JoAnn , Talsma Danielle , Beaumont Lesley , Furlong William , Webber Colin , Barr Ronald
Published: July 2005

Background

Osteopenia has been reported in children surviving acute lymphoblastic leukemia and brain tumors, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a role in the development of this complication. In order to explore that possibility, we examined survivors of brain tumors treated with and without radiation in childhood to investigate associations between radiation, osteopenia, physical activity, health status and overall health‐related quality of life (HRQL).

Procedure

Subjects were survivors of posterior fossa tumors (astrocytoma or medulloblastoma) or optic glioma, < 18 years of age at diagnosis and > 1 year off treatment. Measurements of growth velocity, body composition, bone densitometry, physical activity and HRQL were undertaken.

Results

Twenty‐five (62.5%) of the 40 eligible patients participated in the study. Of the 25 patients, 12 (48%) received radiation therapy (R group) while 13 received no radiation (NR group). Growth hormone (GH) deficiency had been detected in three subjects, one had completed GH therapy while two were still on hormone replacement. The prevalence of osteopenia was 44% in the entire group, and 67% versus 27% in the R and NR groups. Florid osteoporosis was present in 20% of the entire group, more than 40% of the R group but none of the NR group. A significant correlation (P < 0.01) was observed between overall HRQL and Z scores of bone mineral density (BMD) of the lumbar spine. Pain and ambulation/mobility utility scores correlated significantly (P < 0.05) with BMD, while levels of physical activity correlated (P < 0.05) with overall HRQL utility scores.

Conclusions

This pilot study demonstrates that in survivors of brain tumors treated in childhood, radiation therapy is associated with significant loss of bone mineral. Among these survivors, HRQL is less, pain is more severe and ambulation is more restricted in those with low BMD scores. The reduction in HRQL is reflected in diminished physical activity. A larger multi‐center study is needed to confirm these results. © 2005 Wiley‐Liss, Inc.
Synthesis, thermal characterization, and tensile properties of alipharomatic polyesters derived from 1,3‐propanediol and terephthalic, isophthalic, and 2,6‐naphthalenedicarboxylic acid
Authors: Roupakias C. P. , Bikiaris D. N. , Karayannidis G. P.
Published: July 2005

In this work, three alipharomatic polyesters—poly(propylene terephthalate) (PPT), poly(propylene isophthalate) (PPI), and poly(propylene naphthalate) (PPN)—were prepared and studied with the aliphatic diol 1,3‐propanediol and the corresponding aromatic diacids. Their synthesis was performed by the two‐stage melt polycondensation method in a glass batch reactor. The thermal characterization of these polyesters was carried out with different thermal techniques such as simultaneous thermogravimetry/differential thermal analysis, thermomechanical analysis (TMA), and dynamic thermomechanical analysis. From the recorded values for the glass‐transition temperature (Tg) and melting temperature with all the aforementioned techniques, it could be said that they were in good agreement. According to the thermogravimetric results, PPT and PPI showed about the same thermal stability, whereas PPN seemed to be somewhere more thermostable. Remarkably, a transition existed immediately after Tg that was realized by the first derivative of TMA, and it was characterized as a midrange transition. For all polyesters, the average coefficient of linear thermal expansion was calculated with TMA. The secondary relaxations Tβ and Tγ, recorded with dynamic mechanical thermal analysis, were mainly affected by the kinds of monomers. Concerning the mechanical properties, PPN had the highest tensile strength at break, whereas PPT had the highest elongation at break. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3998–4011, 2005
Comparison of the properties of waterborne polyurethane/multiwalled carbon nanotube and acid‐treated multiwalled carbon nanotube composites prepared by in situ polymerization
Authors: Kwon Jiyun , Kim Hando
Published: July 2005

A series of waterborne polyurethane (WBPU)/multiwalled carbon nanotube (CNT) and WBPU/nitric acid treated multiwalled carbon nanotube (A‐CNT) composites were prepared by in situ polymerization in an aqueous medium. The optimum nitric acid treatment time was about 0.5 h. The effects of the CNT and A‐CNT contents on the dynamic mechanical thermal properties, mechanical properties, hardness, electrical conductivity, and antistatic properties of the two kinds of composites were compared. The tensile strength and modulus, the glass‐transition temperatures of the soft and hard segments (Tgs and Tgh, respectively), and ΔTg (Tgh − Tgs) of WBPU for both composites increased with increasing CNT and A‐CNT contents. However, these properties of the WBPU/A‐CNT composites were higher than those of the WBPU/CNT composites with the same CNT content. The electrical conductivities of the WBPU/CNT1.5 and WBPU/A‐CNT1.5 composites containing 1.5 wt % CNTs (8.0 × 10−4 and 1.1 × 10−3 S/cm) were nearly 8 and 9 orders of magnitude higher than that of WBPU (2.5 × 10−12 S/cm), respectively. The half‐life of the electrostatic charge (τ1/2) values of the WBPU/CNT0.1 and WBPU/A‐CNT0.1 composites containing 0.1 wt % CNTs were below 10 s, and the composites had good antistatic properties. From these results, A‐CNT was found to be a better reinforcer than CNT. These results suggest that WBPU/A‐CNT composites prepared by in situ polymerization have high potential as new materials for waterborne coatings with good physical, antistatic, and conductive properties. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3973–3985, 2005
Isobaric cure shrinkage behaviors of epoxy molding compound in isothermal state
Authors: Hwang Sheng‐Jye , Chang Yi‐San
Published: July 2005

The warpage of plastic‐encapsulated IC packages after molding is believed to be induced by thermal and cure shrinkage of epoxy molding compound (EMC). To study the warpage behaviors of EMC, the amount of cure‐induced shrinkage needs to be understood. Volume shrinkage behaviors induced by cure reaction of EMC in isothermal and isobaric states were studied with a differential scanning calorimeter (DSC) and a pressure–temperature‐controlled dilatometer. The results show that higher pressure induce more volume shrinkage under fixed temperature but the difference of volume shrinkage under different pressure levels doesn't obey the principle of linearity. It is observed that the amount of chemical volume shrinkage at 145 °C is higher than those under three other temperatures: 160, 175, and 190 °C. The chemical volume shrinkage of EMC is found to be very process dependent. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2392–2398, 2005
Computing the full nonrigid group of tetra‐tert‐butyltetrahedrane using wreath product
Authors: Darafsheh Mohammad Reza , Ashrafi Ali Reza , Darafsheh Arash
Published: July 2005

The concept of symmetry group of nonrigid molecules as a permutation‐inversion group was formulated first by Longuet‐Higgins, although earlier works suggested the need for such a framework. Then Balasubramanian showed that these groups could be cast into elegant algebraic structures known as the wreath product of groups. In this study, we apply a similar method to that used by Balasubramanian to find the nonrigid group (NRG) of tetra‐tert‐butyltetrahedrane. Using the group theory package GAP, we calculate the conjugacy classes and character table of this molecule. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Quantum wave packet calculation of reaction probabilities, cross sections, and rate constants for the C(1D) + HD reaction
Authors: Gogtas Fahrettin , Bulut Niyazi , Akpinar Sinan
Published: July 2005

The time‐dependent real wave packet method has been used to study the C(1D) + HD reaction. The state‐to‐state and state‐to‐all reactive scattering probabilities for a broad range of energies are calculated at zero total angular momentum. The probabilities for J > 0 are estimated from accurately computed J = 0 probabilities by using the J‐shifting approximation. The integral cross sections for a large energy range, and thermal rate constants are calculated. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Theoretical study of the formation reaction of the methyl vinyl ketone: A conformational approach
Authors: Ramírez‐Ramírez Víctor M. , Nebot‐Gil Ignacio
Published: July 2005

The formation reaction of both isomers of the methyl vinyl ketone (MVK) from the corresponding alkoxy radicals was investigated by means of theoretical methods based on quantum chemistry. Perturbative unrestricted Möller–Plesset (UMP2) and density functional methods B3LYP and BH and HLYP were used to obtain the stationary points on the potential energy surface. In addition to this, the interconversion reaction between both isomers of the MVK was studied, characterizing the corresponding transition state. A conformational study was done, and the energy and geometry of the stationary points located were analyzed by means of ab initio calculations. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Quantitative determination of endogenous sorbitol and fructose in human nerve tissues by atmospheric‐pressure chemical ionization liquid chromatography/tandem mass spectrometry
Authors: Liang H. R. , Takagaki T. , Foltz R. L. , Bennett P.
Published: July 2005

Attachment of anions to sorbitol and fructose has been shown to enhance sensitivity in both electrospray ionization (ESI) and atmospheric‐pressure chemical ionization (APCI) mass spectrometry. The post‐column addition of CHCl3 produced Cl‐adducts of sorbitol and fructose but their signals were suppressed due to the elevated background. Different chlorinated compounds and different additive methods were systematically investigated to form more abundant Cl‐adduct precursor ions and deprotonated product ions. The major causes of the high background were explored and effective methods were developed to improve the signal‐to‐noise ratios and reproducibility. The compositions of mobile phase, percentages of organic modifiers (MeCN, MeOH and water), columns, oven temperature, flow rates and different gradients were investigated to separate sorbitol from fructose along with their isomers including glucose, galactose, mannose, sorbose, mannitol, and dulcitol. The optimized separation was achieved on a Luna 5 µ NH2 100A column (150 × 4.6 mm) using a mobile phase containing MeCN with 0.1% of CH2Cl2 and 50% MeOH in water at a flow rate of 800 µL/min and an oven temperature of 40°C using a gradient liquid chromatography (LC) system. Human nerve tissue samples were extracted by protein precipitation followed by mixed‐mode solid‐phase extraction. The LC/ESI‐MS/MS method produced higher peak intensities than LC/APCI‐MS/MS. However, there were matrix effects from extracted tissues in LC/ESI‐MS/MS but not in LC/APCI‐MS/MS. Consequently, APCI proved to be the more effective method of ionization. Then the LC/APCI‐MS/MS method was fully validated and successfully applied to analysis of clinical samples. The concentrations of endogenous sorbitol and fructose were determined using calibration curves employing sorbitol‐13C6 and fructose‐13C6 as surrogate analytes. The method has provided excellent intra‐ and inter‐assay precision and accuracy with linear ranges of 0.2–80 ng/mg for sorbitol and 1–400 ng/mg for fructose in human nerve tissues. Copyright © 2005 John Wiley & Sons, Ltd.
Fragmentation of oligosaccharide ions with 157 nm vacuum ultraviolet light
Authors: Devakumar Arugadoss , Thompson Matthew S. , Reilly James P.
Published: July 2005

The 157 nm photofragmentation of native and derivatized oligosaccharides was studied in a linear ion trap and in a home‐built matrix‐assisted laser desorption/ionization (MALDI) tandem time‐of‐flight (TOF/TOF) mass spectrometer, and the results were compared with collision‐induced dissociation (CID) experiments. Photodissociation produces product ions corresponding to high‐energy fragmentation pathways; for cation‐derivatized oligosaccharides, it yields strong cross‐ring fragment ions and provides better sequence coverage than low‐ and high‐energy CID experiments. On the other hand, for native oligosaccharides, CID yielded somewhat better sequence coverage than photodissociation. The ion trap enables CID hybrid MS3 experiments on the high‐energy fragment ions obtained from photodissociation. Copyright © 2005 John Wiley & Sons, Ltd.
Novel Ultrananocrystalline Diamond Probes for High‐Resolution Low‐Wear Nanolithographic Techniques
Authors: Kim Keun‐Ho , Moldovan Nicolaie , Ke Changhong , Espinosa Horacio D. , Xiao Xingcheng , Carlisle John A. , Auciello Orlando
Published: July 2005

A hard, low‐wear probe for contact‐mode writing techniques, such as dip‐pen nanolithography (DPN), was fabricated using ultrananocrystalline diamond (UNCD). Molding within anisotropically etched and oxidized pyramidal pits in silicon was used to obtain diamond tips with radii down to 30 nm through growth of UNCD films followed by selective etching of the silicon template substrate. The probes were monolithically integrated with diamond cantilevers and subsequently integrated into a chip body obtained by metal electroforming. The probes were characterized in terms of their mechanical properties, wear, and atomic force microscopy imaging capabilities. The developed probes performed exceptionally well in DPN molecular writing/imaging mode. Furthermore, the integration of UNCD films with appropriate substrates and the use of directed microfabrication techniques are particularly suitable for fabrication of one‐ and two‐dimensional arrays of probes that can be used for massive parallel fabrication of nanostructures by the DPN method.
Candida glabrata is unusual with respect to its resistance to cationic antifungal proteins
Authors: Helmerhorst Eva J. , Venuleo Caterina , Beri Anuradha , Oppenheim Frank G.
Published: July 2005

Naturally occurring salivary antifungal proteins have been of major interest, due to their potential to provide the basis for peptide antimycotics effective in combating fungal infections in the oral cavity or elsewhere. We tested the fungistatic activity of a number of cationic antifungal proteins, with major emphasis on histatin 5, a basic protein secreted by the human parotid and submandibular glands. Histatin 5 inhibited the growth of Candida albicans and that of other medically important Candida species, such as C. kefyr, C. krusei, and C. parapsilosis, with IC50 values in the range of 10–20 µg/ml. Two Cryptococcus neoformans strains were also sensitive (IC50 5.2 and 5.6 µg/ml). On the other hand, three C. glabrata strains (ATCC 90030, 2001 and 64677) were entirely insensitive to histatin 5 (IC50>225 µg/ml). Four genetically very similar species to C. glabrata, Candida castelli (CBS 4332), Saccharomyces cerevisiae (S288C, BY4741 and CBS 1171), Kluyveromyces delphensis (CBS 2170) and Kluyveromyces bacillisporus (CBS 7720) were all sensitive to histatin 5 (IC50 2.6–64.6 µg/ml). C. glabrata was also insensitive to other members of the histatin family; histatin 1, 3 and P‐113 (IC50 values in all cases >225 µg/ml). In addition, two entirely different cationic antifungal proteins originating from frog skin, PGLa and magainin 2, also showed a strong reduced activity toward this fungus. Besides the well‐described inherent resistance of C. glabrata to azole‐derived antifungal agents, our studies indicate that this species is also able to withstand the otherwise detrimental activities of cationic antifungal proteins. Copyright © 2005 John Wiley & Sons, Ltd.
The N‐terminal domain of Escherichia coli ClpB enhances chaperone function
Authors: Chow I-Ting , Barnett Micheal E. , Zolkiewski Michal , Baneyx François
Published: July 2005

ClpB/Hsp104 collaborates with the Hsp70 system to promote the solubilization and reactivation of proteins that misfold and aggregate following heat shock. In Escherichia coli and other eubacteria, two ClpB isoforms (ClpB95 and ClpB80) that differ by the presence or absence of a highly mobile 149‐residues long N‐terminus domain are synthesized from the same transcript. Whether and how the N‐domain contributes to ClpB chaperone activity remains controversial. Here, we show that, whereas fusion of a 20‐residues long hexahistidine extension to the N‐terminus of ClpB95 interferes with its in vivo and in vitro activity, the same tag has no detectable effect on ClpB80 function. In addition, ClpB95 is more effective than ClpB80 at restoring the folding of the model protein preS2‐β‐galactosidase as stress severity increases, and is superior to ClpB80 in improving the high temperature growth and low temperature recovery of dnaK756 ΔclpB cells. Our results are consistent with a model in which the N‐domain of ClpB95 maximizes substrate processing under conditions where the cellular supply of free DnaK–DnaJ is limiting.
Selective inhibition of divergent seryl‐tRNA synthetases by serine analogues
Authors: Ahel Dragana , Slade Dea , Mocibob Marko , Söll Dieter , Weygand-Durasevic Ivana
Published: July 2005

Seryl‐tRNA synthetases (SerRSs) fall into two distinct evolutionary groups of enzymes, bacterial and methanogenic. These two types of SerRSs display only minimal sequence similarity, primarily within the class II conserved motifs, and possess distinct modes of tRNASer recognition. In order to determine whether the two types of SerRSs also differ in their recognition of the serine substrate, we compared the sensitivity of the representative methanogenic and bacterial‐type SerRSs to serine hydroxamate and two previously unidentified inhibitors, serinamide and serine methyl ester. Our kinetic data showed selective inhibition of the methanogenic SerRS by serinamide, suggesting a lack of mechanistic uniformity in serine recognition between the evolutionarily distinct SerRSs.
Mapping of C‐termini of V‐ATPase subunits by in vivo‐FRET measurements
Authors: Seidel Thorsten , Golldack Dortje , Dietz Karl-Josef
Published: July 2005

The plant V‐ATPase is a protein complex of 13 different VHA‐subunits and functions as ATP driven motor that electrogenically translocates H+ into endomembrane compartments. The central rotor extends into the hexameric head that is fixed by peripheral stators to an eccentric membrane domain. The localization and orientation of VHA‐subunits of the head and peripheral stalk region were investigated by in vivo fluorescence resonance energy transfer (FRET). To this end, VHA‐E, VHA‐G, VHA‐H of the peripheral stalks as well as subunits VHA‐A and VHA‐B were C‐terminally fused to cyan (CFP) and yellow fluorescent protein (YFP). Protoplasts transfected with FRET‐pairs of CFP‐donor and YFP‐acceptor fluorophores fused to VHA‐subunits were analysed for FRET by laser scanning microscopy. The result of the C‐termini mapping allows to refine the arrangement and interaction of the subunits within the V‐ATPase complex in vivo. Furthermore, expression of fused VHA‐E and VHA‐H stimulated acidification of protoplast vacuoles, while other constructs had no major effect on vacuolar pH tentatively indicating a regulatory role of these subunits in plants.