bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense peptide nucleic acid‐mediated knockdown of the p75 neurotrophin receptor delays motor neuron disease in mutant SOD1 transgenic mice
Authors: Turner Bradley J. , Cheah Irwin K. , Macfarlane Katherine J. , Lopes Elizabeth C. , Petratos Steven , Langford Steven J. , Cheema Surindar S. 
Published: October 2003

AbstractRe‐expression of the death‐signalling p75 neurotrophin receptor (p75NTR) is associated with injury and neurodegeneration in the adult nervous system. The induction of p75NTR expression in mature degenerating spinal motor neurons of humans and transgenic mice with amyotrophic lateral sclerosis (ALS) suggests a role of p75NTR in the progression of motor neuron disease (MND). In this study, we designed, synthesized and evaluated novel antisense peptide nucleic acid (PNA) constructs targeting p75NTR as a potential gene knockdown therapeutic strategy for ALS. An 11‐mer antisense PNA directed at the initiation codon, but not downstream gene sequences, dose‐dependently inhibited p75NTR expression and death‐signalling by nerve growth factor (NGF) in Schwann cell cultures. Antisense phosphorothioate oligonucleotide (PS‐ODN) sequences used for comparison failed to confer such inhibitory activity. Systemic intraperitoneal administration of this antisense PNA to mutant superoxide dismutase 1 (SOD1G93A) transgenic mice significantly delayed locomotor impairment and mortality compared with mice injected with nonsense or scrambled PNA sequences. Reductions in p75NTR expression and subsequent caspase‐3 activation in spinal cords were consistent with increased survival in antisense PNA‐treated mice. The uptake of fluorescent‐labelled antisense PNA in the nervous system of transgenic mice was also confirmed. This study suggests that p75NTR may be a promising antisense target in the treatment of ALS.
Caspase cleavage of the amyloid precursor protein modulates amyloid β‐protein toxicity
Authors: Lu Daniel C. , Soriano Salvador , Bredesen Dale E. , Koo Edward H. 
Published: October 2003

AbstractThe amyloid β‐protein precursor (APP) is proteolytically cleaved to generate the amyloid β‐protein (Aβ), the principal constituent of senile plaques found in Alzheimer's disease (AD). In addition, Aβ in its oligomeric and fibrillar forms have been hypothesized to induce neuronal toxicity. We and others have previously shown that APP can be cleaved by caspases at the C‐terminus to generate a potentially cytotoxic peptide termed C31. Furthermore, this cleavage event and caspase activation were increased in the brains of AD, but not control, cases. In this study, we show that in cultured cells, Aβ induces caspase cleavage of APP in the C‐terminus and that the subsequent generation of C31 contributes to the apoptotic cell death associated with Aβ. Interestingly, both Aβ toxicity and C31 pathway are dependent on the presence of APP. Both APP‐dependent Aβ toxicity and C31‐induced apoptotic cell death involve apical or initiator caspases‐8 and ‐9. Our results suggest that Aβ‐mediated toxicity initiates a cascade of events that includes caspase activation and APP cleavage. These findings link C31 generation and its potential cell death activity to Aβ cytotoxicity, the leading mechanism proposed for neuronal death in AD.
Intensive In‐Center Hemodialysis for Children: A Case for Longer Dialysis Duration
Authors: Bell Lorraine , Espinosa Pauline 
Published: October 2003

Background:  Children with renal failure need their dialysis time optimized. Although traditional surrogate markers of outcome in pediatric patients have been growth and development, increasing attention is being focused on cardiovascular risk factors, such as hypertension, volume overload, malnutrition, and elevated calcium (Ca) and phosphorus (P) levels. We have previously shown catch‐up growth without growth hormone, in children undergoing long intermittent hemodialysis. Recently we analyzed retrospectively cardiovascular risk factors in patients treated with this regimen. Methods:  Patients starting dialysis between 1997 and 2001 and on dialysis at least 6 months were evaluated. Charts were reviewed for Ca, P, parathyroid hormone (PTH), albumin, hemoglobin and blood pressure levels, Ca intake, blood pressure medications, dialysis time, and clearance and ultrafiltration rates. Means were calculated for 6‐ month intervals, up to 36 months. Results:  Mean equilibrated dialyzer Kt/V

urea

ranged from 1.9 to 2.1, and mean weekly dialysis time for oliguric patients varied from 14.8 to 16.3 hr, with average hourly ultrafiltration rates from 0.3 to 0.4 L. Mean values for P and Ca × P were below 1.8 mM and 4.4 mmol 2/L2, respectively. Mean hemoglobin levels were 115 to 126 g/L, albumin 39 to 41 g/L, and PTH 156 to 231 pg/mL. Most patients had normal predialysis blood pressures.Conclusions:  In this pediatric cohort, intensive center hemodialysis was associated with excellent growth, nutrition, Ca, P, and anemia control and reasonable blood pressure values. Large multicenter studies are needed to better determine optimal dialysis therapy for children.
Hepatitis B Virus Vaccine Response in Hemodialysis: Baseline Patient Characteristics
Authors: Chin Andrew I. 
Published: October 2003

Background:  Hepatitis B virus (HBV) vaccination is recommended for all individuals with renal failure. Nevertheless, the response rate for this vaccine in hemodialysis (HD) patients is low, ranging from 50% to 80%. The goal of this study was to determine patient characteristics at the initiation of HD that influence HBV vaccine response. Methods:  Patients new to HD in an urban population in the United States were retrospectively examined. Analyzed patients were HBV antibody and antigen negative and hepatitis C virus antibody negative at the start of HD, who received HBV recombinant vaccine. Nonresponse was defined as failure to seroconvert (>10 UI/L) after six deltoid intramuscular injections of vaccine. Response was defined as a lasting seroconversion (at least two consecutive positive titers) with ≤6 injections. Demographic, laboratory, and kinetic modeling data were examined. Results:  A total of 33 nonresponders and 64 responders were identified. Univariate analysis demonstrated that nonresponders were older (59 vs. 51 years), had a higher prevalence of diabetes mellitus (DM) (70 vs. 39%), had lower serum albumin levels (3.2 vs. 3.3 g/dL), and had higher dry weights (84 vs. 71 kg) than responders at HD start. In addition, nonresponders had lower normalized protein catabolic rates (0.74 vs. 0.85 g/kg/day) and lower (single‐pool) spKt/V

urea

values (0.95 vs. 1.19). Nonresponders had lower serum creatinine levels than responders, despite the greater dry weights. In a multiple logistic analysis model, the presence of DM, age ≥ 55 years, body weight ≥80 kg, and normalized protein catabolic rate ≤0.75 g/kg/day were associated with HBV vaccination nonresponse. At the end of the vaccination period, nonresponders versus responders continued to have lower serum albumin (3.5 vs. 3.8 g/dL) and creatinine levels (7.8 vs. 10.0 mg/dL) and spKt/V

urea

(1.27 vs. 1.39). Conclusion:  Hepatitis B vaccine nonresponders on HD are older, are more likely to have DM, are more malnourished, and have lower spKt/Vurea than responders. Nonresponders may also have a different body composition with a lower ratio of lean to total body mass.
Relation between Access‐Related Infection and Preinfection Serum Albumin Concentration in Patients on Chronic Hemodialysis
Authors: Adeniyi Oladipo A. , Tzamaloukas Antonios H. 
Published: October 2003

Background:  Hemodialysis (HD) access‐related infection is a major cause of morbidity and mortality in HD patients. We tested whether hypoalbuminemia is a risk factor for HD access infection and whether mortality of HD catheter infection is affected by removal of the infected catheter. Methods:  We analyzed the records of 87 patients on chronic HD who were hospitalized for HD access‐related infection. We obtained data on age, sex, preinfection serum albumin level, comorbidities, complications, infecting organism, type of infection, mode of management, and mortality. We compared preinfection serum albumin levels in 79 patients with HD access infection with the serum albumin levels of 198 control patients on chronic HD without HD access infection admitted to the hospital during the same time for other reasons. In the HD catheter infection subgroup, we compared mortalities between patients treated with catheter removal plus antibiotics as the primary mode of management and those treated initially with antibiotics alone. Results:  Preadmission serum albumin level was lower in the HD access infection group (2.4 ± 0.6 g/dL) than in the control group (3.2 ± 0.6 g/dL, P < 0.0001). Logistic regression identified preadmission serum albumin level as a strong independent predictor of HD access infection. In a logistic regression model, with age, sex, HIV status, diabetes, and type of HD vascular access (excluding arterovenous fistula) as the covariates, the odds ratio of HD access infection was 9.8 (95% confidence interval [CI] 4.9–19.7) for a serum albumin level ≤ 3.0 g/dL (P < 0.0001), 10.4 (95% CI 4.97–21.6) for a serum albumin level ≤ 2.5 g/dL (P < 0.0001), and 28.0 (95% CI 5.8–135.9) for a serum albumin level ≤ 2.0 g/dL (P < 0.0001). Case mortality was 25.0% (4/16) in patients with tunneled HD catheter infection initially treated with antibiotics alone and 2.8% (2/71) in those treated with catheter removal plus antibiotics at the time of presentation (P = 0.0096). Conclusion:  Hypoalbuminemia is associated with increased risk of HD access infection. Treatment of HD access infection with antibiotics alone is associated with increased risk of death.
Air‐Bubble Method of Locking Central‐Vein Catheters for Prevention of Hub Colonization: A Pilot Study
Authors: Twardowski Zbylut J. , Reams Garry , Prowant Barbara F. , Moore Harold L. , Van Stone John C. 
Published: October 2003

Background:  The major source of catheter‐associated bacteremia is contamination of the catheter hub during connection–disconnection procedures. A new method of catheter locking has been developed wherein anticoagulant is injected first, followed by a 0.1‐mL air bubble and 0.9 mL of bactericidal solution. The anticoagulant is then located at the catheter tip and the bactericidal solution is located at the catheter hub. The air bubble prevents mixing of the two solutions. The bactericidal solution was acidified concentrated saline (ACS). The 27% saline solution has a pH of 2.0. ACS was chosen because it is theoretically harmless if injected in the amount used to lock the catheter lumens. The goals of this pilot study were to determine whether the new method of catheter locking is easy to perform with available syringes and whether eventual injection of the experimental solution is well tolerated. Methods:  Ten patients were randomly assigned, either to heparin lock (5 patients, 62 treatments) or air‐bubble method (5 patients, 56 treatments). In the control group, the catheters were locked with heparin, 5000 U/mL. In the experimental group, the catheters were locked with heparin, air bubble, and ACS. Altogether, the lumens were overfilled by 0.2 mL. Results:  Compared to the routine method, the experimental method required a 1‐ to 2‐min‐longer procedure time. There were no errors in proper sequence of injections into the lumina. There were no episodes of bacteremia related to hub contamination in either group. In the air‐bubble group, there was one case of bacteremia associated with purulent drainage from the exit and the same organism in both cultures. In three instances in each group, the locking solution could not be aspirated and was injected without any subjective symptoms or objective signs. Conclusion:  We conclude that the air‐bubble method of locking central‐vein catheters is easy to perform. In three instances of air‐bubble and ACS injection, there were no adverse effects. A full‐scale prospective randomized study is feasible and warranted.
Lipoprotein (a) in Chronic Renal Failure: Effect of Maintenance Hemodialysis
Authors: Kalra Om Prakash , Khaira Ambar , Gambhir Jasvinder Kaur , Agarwal Sunil , Bhargava Satish Kumar 
Published: October 2003

Background:  Coronary artery disease accounts for significant morbidity and mortality in patients with chronic kidney disease (CKD). Besides the higher prevalence of traditional risk factors, several uremia‐related factors may play a role in accelerated atherosclerosis, such as elevated levels of lipoprotein (a) (Lp(a)). The effect of maintenance hemodialysis (MHD) on Lp(a) levels is not well understood. The present work was carried out to study the Lp(a) levels in Stage 4 and Stage 5 CKD patients as well as the effect of MHD on Lp(a) levels in patients with Stage 5 CKD. Methods:  The study subjects included 15 patients with Stage 4 CKD, 15 patients with Stage 5 CKD, and 15 age‐ and sex‐matched healthy controls. Plasma Lp(a) was measured by ELISA in all the subjects at the time of entry into the study and after 4 weeks of MHD in patients with Stage 5 CKD. Patients on MHD were dialyzed two to three times weekly for 4 hr during each session. Results:  Mean Lp(a) levels were significantly higher in patients with CKD than in control patients. In patients with Stage 4 CKD, the Lp(a) level was 34.0 ± 19.5 mg/dL, whereas in Stage 5 CKD the level was 49.0 ± 30.9 and in healthy controls it was 22.2 ± 16.4. In patients with Stage 5 CKD, 4 weeks of MHD led to a significant fall in Lp(a) levels by 23.6% (P < 0.001). Conclusions:  The results of this study show that increases in Lp(a) levels start early during the course of CKD and become more pronounced with increased severity of disease. Initiation of MHD lowers Lp(a) levels and may have a long‐term beneficial effect on cardiovascular morbidity and mortality.
Impact of Predialysis Care on Clinical Outcomes
Authors: Yeoh Hock H. , Tiquia Herbert S. , Abcar Antoine C. , Rasgon Scott A. , Idroos Mohamed L. , Daneshvari Sam F. 
Published: October 2003

Introduction:  A structured predialysis multidisciplinary team program is beneficial in improving quality of life in patients with end‐stage renal disease (ESRD). Educating pre‐ESRD patients about their disease is vital in their care. Patients who can identify signs and symptoms of impending problems can seek help and avoid complications that may lead to hospital admissions. Our dialysis center offers two predialysis classes in a structured format. The first class is for those patients with mild to moderate renal disease, whereas the second class is for those with advanced renal disease who are expected to need dialysis in 3 to 6 months. The patients are followed by a multidisciplinary team once they are enrolled in our chronic kidney disease program. Methods:  We retrospectively reviewed all the charts of patients who started dialysis at our center between 1997 and 2000. We identified 68 patients who participated in the predialysis education program and 35 patients who did not because of late referral or refusal to participate. We compared these two groups over a 100‐day period (10 days before initial dialysis and 90 days after), for hospitalizations, emergency room (ER) visits, and dialysis access placement. Patients' comorbid conditions, complications, and length of hospitalizations were extracted from the medical records. Results:  The 68 patients who completed the predialysis program had an average age of 60.3 years, a total of 96 hospital days, and 39 ER visits. Average length of hospital stay for these patients was 1.4 days. Three patients (4.4%) required placement of temporary catheters for the initial dialysis. Fifty‐one percent of these patients had diabetes mellitus. The 35 patients of average age of 54.9 years who did not go through the program had 347 total hospital days and 39 ER visits. Average length of hospitalization was 9.9 days. Thirteen patients (37%) required temporary catheters for initial dialysis. This group included 16 patients (45.7%) with diabetes. Conclusion:  Patients who participated in a multidisciplinary predialysis education program had fewer complications, ER visits, and hospitalizations. They also had fewer temporary catheter placements, shorter hospital stays, and reduced costs associated with initial dialysis.
Helicobacter‐induced Gastritis in Mice Not Expressing Metallothionein‐I and II*
Authors: Tran Cuong D. , Huynh Hien , Van Den Berg Maartje , Van Der Pas Mechtelt , Campbell M. A. Fiona , Philcox Jeffrey C. , Coyle Peter , Rofe Allau M. , Butler Ross N. 
Published: October 2003

ABSTRACTBackground.  Helicobacter pylori a primary cause of gastritis and peptic ulcer disease, is associated with increased production of reactive oxygen species within the gastric mucosa. Metallothionein (MT), a low‐molecular‐weight, cysteine‐rich, metal‐binding ligand, has been shown to sequester reactive oxygen species and reduce tissue damage. This study investigates the role of MT in H. pylori‐induced gastritis in mice.Materials and Methods.  Control (MT+/+) and MT‐null (MT–/–) mice were inoculated with either 1 × 108H. pylori or H. felis, and were infected for 4, 8 and 16 weeks or 8 weeks, respectively. H. pylori load was determined by culture. Myloperoxidase activity and MT levels were also determined.Results.  The stomachs of H. felis‐infected mice were more severely inflamed than those of H. pylori‐infected mice. H. felis‐induced gastritis was more severe (p = .003) in MT–/– than in MT+/+ mice. MT–/– mice also had higher (60%; p < .05) H. pylori loads than MT+/+ mice 4 weeks after infection but not 8 or 16 weeks after infection. Myloperoxidase activity with H. pylori was similar between MT+/+ and MT–/– mice. Thirty‐three per cent greater (p < .05) myloperoxidase activity was observed in MT–/– than in MT+/+ mice infected with H. felis. In MT+/+ mice infected with H. pylori, liver MT was increased by 33 and 39% (p < .05) at 8 and 16 weeks, respectively, whereas gastric MT increased by 46% (p < .05) at 4 weeks and declined to baseline levels at 8 and 16 weeks.Conclusions.  Mice lacking MT are more susceptible to H. pylori colonization and gastric inflammation, indicating that MT may be protective against H. pylori‐induced gastritis.
Inhibition of Helicobacter pylori‐induced Nuclear Factor‐kappa B Activation and Interleukin‐8 Gene Expression by Ecabet Sodium in Gastric Epithelial Cells
Authors: Kim Jung Mogg , Kim Joo Sung , Jung Hyun Chae , Oh Yu‐Kyoung , Kim Nayoung , Song In Sung 
Published: October 2003

ABSTRACTBackground.  Helicobacter pylori stimulates nuclear factor‐kappa B (NF‐κB) activation and chemokine interleukin‐8 (IL‐8) expression in gastric epithelial cells. Ecabet sodium (ecabet), a locally acting antiulcer drug, is known to have anti‐H. pylori activity. However, there is little understanding of how ecabet induces anti‐inflammatory activity in gastric epithelial cells infected with H. pylori. The aim of this study was to investigate the effects of ecabet on IL‐8 gene expression and NF‐κB activation in human gastric epithelial cells infected with H. pylori.Materials and Methods.  After Hs746T, MKN‐45, or SNU‐5 gastric epithelial cell lines had been infected with cagA+cytotoxin+H. pylori in the presence of ecabet, IL‐8 mRNA expression was assessed by quantitative reverse transcription–polymerase chain reaction, and IL‐8 secretion was measured by enzyme‐linked immunosorbent assay. NF‐κB and inhibitory kappa B‐alpha (IκBα) signals were assayed by electrophoretic mobility shift assay and Western blot, respectively. The activation of NF‐κB and IL‐8 reporter genes was determined by luciferase assay.Results.  Ecabet showed no antimicrobial activiy against Gram‐positive or ‐negative bacteria. However, ecabet inhibited transcription of the IL‐8 gene and secretion of IL‐8 by gastric epithelial cells infected with H. pylori at a concentration of 5 µg/ml. Moreover, ecabet inhibited the activation of NF‐κB and the degradation of IκBα in gastric epithelial cells in response to H. pylori infection. In addition, the NF‐κB signal inhibited by ecabet was comprised predominantly of heterodimers of p65/p50.Conclusions.  Ecabet inhibited H. pylori‐induced IL‐8 gene transcription and secretion by suppressing the NF‐κB signal. This inhibition might be one pathway by which ecabet exerts its anti‐inflammatory effect on H. pylori‐induced gastric inflammation.
Placental Acquisition of Maternal Specific IgG and Helicobacter pylori Colonization in Infancy
Authors: Bunn James E. G. , Thomas Julian E. , Harding Marilyn , Coward W. Andrew , Weaver Lawrence T. 
Published: October 2003

ABSTRACTBackground.  Colonization with Helicobacter pylori generally occurs in infancy, and the microorganism is often acquired from close family members. Rate of infant colonization may be affected by maternal immune status.Methods.  To investigate the potential protective effect of anti‐H. pylori immunoglobulin G (IgG) acquired via the placenta, 65 mothers and their infants were studied from the infant's birth for 1 year. Circulating IgG antibodies were measured by enzyme‐linked immunosorbent assay (ELISA) in cord blood and every 8 weeks. Immunoblotting was performed on sera from infants with significant increases in IgG levels. Rate of infant H. pylori colonization was measured by 13C urea breath tests every 4 weeks from the age of 12 weeks.Results.  Maternal and infant cord blood specific IgG levels were correlated (R2 = .747, p < .001). Infant H. pylori specific IgG fell 5‐fold compared to maternal levels over the first 6 months of life, and rose subsequently in many cases, with the development of novel immunoblot patterns. There were no significant associations between the age at first positive urea breath test and maternal or infant cord specific H. pylori IgG levels.Conclusions.  Transplacentally acquired specific IgG antibody does not protect infants from colonization by H. pylori.