bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of TNF-α gene polymorphisms with systemic lupus erythematosus in Taiwanese patients
Authors: Lin Y-J , Chen R-H , Wan L , Sheu JJ-C , Huang C-M , Lin C-W , Chen S-Y , Lai C-H , Lan Y-C , Hsueh K-C , Tsai C-H , Lin T-H , Huang Y-M , Chao K , Chen D-Y , Tsai F-J 
Published: September 2009

Tumour necrosis factor-α (TNF-α), an important proinflammatory cytokine, exerts a variety of physiological and pathogenic effects that lead to tissue destruction. Studies on the association of TNF-α genetic polymorphisms with systemic lupus erythematosus (SLE) have yielded inconclusive results. We investigated the association of TNF-α genetic polymorphisms (−1031T/C, −863C/A, −857T/C, −308A/G and +489A/G) with SLE in Taiwanese patients and controls. Our results indicate that 1) the frequency of the A-allele at −863 position was significantly higher in SLE patients (odds ratio = 1.46; 95% CI = 1.02–2.08); 2) the frequency of the A-allele at +489 position was significantly higher in SLE patients (odds ratio = 1.79; 95% CI = 1.21–2.65); 3) the AA or GA genotype frequencies at +489 position were significantly increased in SLE patients (AA genotype: odds ratio = 11.20; 95% CI = 1.36–92.55; GA genotype: odds ratio = 1.63; 95% CI = 1.03–2.58); 4) no significant association of TNF-α haplotypic distributions was observed, except for the haplotypes TCCGA, CACGA and CCCGG; and 5) the genotype frequency of the polymorphisms at −1031 was significantly different in patients with antinuclear antibodies ( P = 0.022). The allele and genotype frequencies of the polymorphisms at −863 were not significantly different. The genotype frequency of the polymorphisms at −857 was significantly different in patients with haematological disorder ( P = 0.025). The frequency of A allele of the polymorphisms at −308 was significantly increased in patients with malar rash ( P = 0.033), discoid rash ( P = 0.023), photosensitivity ( P = 0.037), oral ulcers ( P = 0.002) and serositis ( P = 0.029). The genotype frequency of the polymorphisms at +489 was significantly different in patients with discoid rash and photosensitivity (data not shown; discoid rash, P = 0.031; photosensitivity, P = 0.044). These results suggest that TNF-α genetic polymorphisms contribute to SLE susceptibility in the Taiwanese population.
Catastrophic antiphospholipid syndrome in a patient with Down syndrome
Authors: Medina Gabriela , Calleja Consuelo , Morán Massiel , Vera-Lastra Olga , Jara Luis J 
Published: September 2009

We report a patient with Down syndrome, under treatment with carbamazepine, levopromazine and clonazepam. After urinary infection he developed glans necrosis requiring excision of prepuce. Six hours post surgery he presented right-hand ischemia followed by arterial and venous thrombosis of the right thoracic extremity. Later, he progressed to a compartment syndrome and presented ischemia of toes. All the clinical manifestations developed over a week. Anticardiolipin (aCL) antibodies, lupus anticoagulant and perinuclear antineutrophil antibodies were positive. Anticoagulant and immunosuppressive treatment were initiated. Owing to the failure of both treatments, the patient underwent amputation of right hand and a toe. Histopathology revealed recent and old thrombosis of medium- and small-sized vessels without vasculitis. Diagnosis of catastrophic antiphospholipid syndrome (CAPS) was made. At present, the patient continues on oral anticoagulants, IgG aCL remains positive, and no further episodes of thromboses have been observed after 4 years of follow-up. To our knowledge, this is the first case of CAPS in a patient with Down syndrome.
Ultraviolet B exposure of peripheral blood mononuclear cells of patients with systemic lupus erythematosus inhibits DNA methylation
Authors: Wang GS , Zhang M , Li XP , Zhang H , Chen W , Kan M , Wang YM 
Published: September 2009

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especially ultraviolet B (UVB) 290–320 nm) is known to induce exacerbation of disease. DNA methylation regulates gene expression, and hypomethylation is associated with abnormal cell function in SLE. The purpose of this study was to investigate the effect of UVB on DNA methylation in SLE and its significance in the pathogenesis of SLE. Forty-five patients with SLE and 20 healthy controls were enrolled in the study, which involved the investigation of DNA methylation and DNA methyltransferase 1 (DNMT1) of peripheral blood mononuclear cells with UVB irradiation. Our results demonstrate the following: The level of DNA methylation in patients with SLE was lower than that in the control group. DNA methylation was decreased after UVB irradiation at different dosages especially in patients with marlar rashes and leucopenia, but no significant difference was observed in the DNMT1 mRNA expression. DNA methylation levels in patients with active SLE were more sensitive to UVB. In conclusion, UVB exposure is able to inhibit DNA methylation, which subsequently takes part in the pathogenesis of SLE.
Prevalence, risk factors and outcome of digital gangrene in 2684 lupus patients
Authors: Liu A , Zhang W , Tian X , Zhang X , Zhang F , Zeng X 
Published: September 2009

The aim of the study is to assess the clinical characteristics, risk factors and outcome of patients with systemic lupus erythematosus (SLE) complicated with digital gangrene. In all, 2684 consecutive SLE inpatients admitted to Peking Union Medical College Hospital from December 1997 to August 2007 were studied. Demographic data, clinical features, laboratory findings as well as therapeutic regimens were systematically reviewed and a database was established. Cases with digital gangrene were identified and followed up. 1) Eighteen patients with SLE were complicated with digital gangrene, the average age at event was 33.1 ± 11.8 years and the average disease duration was 99.1 ± 60.1 months. 2) Patients with SLE, with long disease duration (≥4 years), Raynaud’s phenomenon and elevated serum C-reactive protein (CRP) were more likely to develop digital gangrene, P = 0.006, 0.001, and 0.031, respectively, OR = 1.03 (95% CI 1.01, 1.04), 35.76 (95% CI 4.67, 273.83) and 9.93 (95% CI 1.23, 80.30), respectively. 3) Fifteen gangrene patients started prednisone ≥1 mg/kg/d, and 18 were treated with cyclophosphamide, although 8 cases failed and ultimately received digital amputation. Prompt corticosteroid treatment (prednisone ≥1 mg/kg/d started within 3 weeks) decreased the hazard of amputation, P = 0.073, HR = 0.13 (95% CI 0.01, 1.21). Long disease duration, Raynaud’s phenomenon and elevated serum CRP were independent predictive factors for SLE to develop digital gangrene. Early and aggressive corticosteroid treatment prevented gangrene from progression and improved prognosis.
Busulfan systemic exposure after oral administration of extemporeanously prepared high-dose busulfan capsules
Authors: Kolbe Karin , Karstens Astrid , Krämer Irene 
Published: September 2009

Purpose. The aim of the study was to analyze patients’ busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation. Methods. Patients were treated with 1 mg/kg body weight BU administered orally every 6h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detection. In addition, in two patients concomitant TDM was executed. BU exposure was monitored concurrently and BU doses were targeted to achieve a steady-state plasma concentration (CSS) of 600—900 ng/mL or 900—1100 ng/mL depending on the underlying disease. In these patients blood samples were obtained 0, 60, 120, 180, 240, and 360 min after the 1st, 5th, 9th, and 13th BU dose and analyzed concurrently. Results. For the six patients monitored retrospectively, the time to reach peak plasma BU concentration (Cmax) ranged from 1 to 5 h (mean 2.4 h). BU Cmax — values varied from 728 to 1807 ng/ mL (mean 1174 ng/mL), and BU clearance (CL/F) from 2.32 to 3.75 mL/min/kg (mean 2.97 mL/min/ kg). The mean BU steady state (CSS) concentration calculated was 973 ng/mL (range 754—1226 ng/mL) with a mean AUC of 5818 ng·h/mL (range 4521— 7171 ng·h/mL). One of the two patients receiving targeted BU doses required an upward dose adjustment. None of the eight patients suffered from vomiting during BU therapy. Conclusions. BU active substance encapsulated without further excipients in gelatine capsules is highly suitable for oral BU therapy. However, therapeutic drug monitoring and BU dose adjustment is still advisable to achieve optimal systemic BU exposure in each individual patient.
A comparison of the rates of cisplatin (cDDP) - induced nephrotoxicity associated with sodium loading or sodium loading with forced diuresis as a preventative measure
Authors: Leu Lily , Baribeault David 
Published: September 2009

Objective. To determine whether forced diuresis and sodium loading or sodium loading alone is better at preventing cisplatin-induced nephrotoxicity. Methods. Records of 92 patients receiving cisplatin >40 mg/m2 and sodium loading with or without mannitol were reviewed to determine the incidence of nephrotoxicity, average decline in creatinine clearance, degree of nephrotoxicity, time to resolution, rates of hospitalization, and electrolyte abnormalities among patients receiving sodium loading or sodium loading with forced diuresis. Results. The mean cisplatin dose was 64.5 mg/m2 with a majority of the subjects receiving treatment for lung cancer. The patients who received sodium loading experienced an average decline in creatinine clearance of 33.9 mL/min versus a decline of 38.9 mL/min in the group receiving forced diuresis and sodium loading (p = 0.09). Incidence of nephrotoxicity, rate of hospitalization and rates of hypokalemia or hypomagnesemia were similar between the groups. Time to resolution of nephrotoxicity was significantly different between the groups, although there were limitations in evaluating this outcome. Majority of the subjects in the sodium loading group experienced NCIC-TC Grade 0 nephrotoxicity, whereas half of the patients in the forced diuresis group experienced Grade 2 nephrotoxicity. Conclusion. We detected no difference in the prevention of cisplatin-induced nephrotoxicity when patients were treated with sodium loading alone or with sodium loading with mannitol. No differences were detected in average decrease in creatinine clearance, incidence of nephrotoxicity, or rates of hypomagnesemia and hypokalemia. The difference in time to resolution of toxicity appeared to be significant, however there were limitations in evaluating this outcome.
Long-term stability of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bag at 4°C
Authors: Athanasopoulos Alexandre , Hecq Jean-Daniel , Vanbeckbergen Danielle , Jamart Jacques , Galanti Laurence 
Published: September 2009

Objectives. Preparation of intravenous solution in advance could be efficient to improve quality assurance, security, time management, and cost saving of drug delivery. The purpose of this study was to investigate the stability of a mixture of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bags at 4°C. Methods. The stability of five bags of solution containing 100 mg tramadol and 10 mg metoclopramide per 100 mL dextrose 5% and stored at 4°C was studied during 32 days and concentrations measured by high performance liquid chromatography-diode array detection. Results. No degradation interference nor modification in retention times were observed throughout the study period. At day 32, tramadol concentration was 96.9% ± 2.1 and metoclopramide 97.2% ± 1.3 of the initial concentration. Conclusion. Based on a shelf-life of 90% residual potency, tramadol and metoclopramide were compatible and stable for at least 32 days at 4°C and can be prepared in advance in a centralized intravenous additive service facility. J Oncol Pharm Practice (2009) 15: 195—200.
Anti-inflammatory effects of simvastatin on adipokines in type 2 diabetic patients with carotid atherosclerosis
Authors: Hu Yun , Tong Guoyu , Xu Wei , Pan Jiajia , Ryan Kathy , Yang Rongze , Shuldiner Alan R. , Gong Da-Wei , Zhu Dalong 
Published: September 2009

Objective: Statins are extensively used for lowering LDL-cholesterol and reducing cardiovascular events. Recent studies have shown that statins have beneficial anti-inflammatory effects. We aimed to determine whether and how adipokines are regulated during statin treatment in type 2 diabetic patients. Method: In this study,we investigated the changes of CRP and inflammation-related adipokines (SAA,IL-6,TNFα and adiponectin) in 23 type 2 diabetic patients with atherosclerosis who received statin therapy, and 20 diabetic patients with atherosclerosis and 14 diabetic patients without atherosclerosis who did not receive statin therapy for a period of three months. Results: By the end of the simvastatin treatment (40 mg, daily), LDL-cholesterol was decreased by 16.7% and HDL-cholesterol was increased by 31.9%. SAA, CRP, TNFα and IL-6 levels were decreased by 31.8%, 66.2%, 53.9% and 14%, respectively and adiponectin was increased by 59.6%, compared with the baseline levels. Interestingly, the decrease of SAA was positively correlated with that of LDL-cholesterol but negatively with HDL-cholesterol during statin treatment. Among the adipokines, the decrease of SAA was positively correlated with TNFα ( r = 0.50, p = 0.016). Conclusion: The results suggest that adipokines may be differentially regulated and independent of cholesterol changes and that adipokines may be a mediator, and the adipose tissue may be a target of statins’ anti-inflammatory effect.
The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling
Authors: Szczur Kathleen , Zheng Yi , Filippi Marie-Dominique 
Published: September 2009

AbstractNeutrophil migration to sites of infection is the first line of cellular defense. A key event of migration is the maintenance of a polarized morphology, which is characterized by a single leading edge of filamentous actin and a contractile uropod devoid of filamentous actin protrusions. Using a mouse model of high Cdc42 activity, we previously demonstrated the importance of Cdc42 activity in neutrophil migration. However, the specific functions of Cdc42 in this process remain to be understood. Using neutrophils genetically deficient in Cdc42, we show that Cdc42 regulates directed migration by maintaining neutrophil polarity. Although it is known to be activated at the front, Cdc42 suppresses protrusions at the uropod. Interestingly, Cdc42 makes use of the integrin CD11b during this process. Cdc42 determines the redistribution of CD11b at the uropod. In turn, using CD11b-null cells and CD11b crosslinking experiments, we show that CD11b modulates myosin light chain phosphorylation to suppress lateral protrusions. Our results uncover a new mechanism in which Cdc42 regulates the uropod through CD11b signaling to maintain polarity in migrating neutrophils. It also reveals new functions for CD11b in neutrophil polarity.
The therapeutic effect of bone marrow–derived liver cells in the phenotypic correction of murine hemophilia A
Authors: Yadav Neelam , Kanjirakkuzhiyil Sumod , Kumar Suresh , Jain Manish , Halder Ashutosh , Saxena Renu , Mukhopadhyay Asok 
Published: September 2009

Abstract
The transdifferentiation of bone marrow cells (BMCs) into hepatocytes has created enormous interest in applying this process to the development of cellular medicine for degenerative and genetic diseases. Because the liver is the primary site of factor VIII (FVIII) synthesis, we hypothesized that the partial replacement of mutated liver cells by healthy cells in hemophilia A mice could manage the severity of the bleeding disorder. We perturbed the host liver with acetaminophen to facilitate the engraftment and hepatic differentiation of lineage-depleted enhanced green fluorescent protein-expressing BMCs. Immunohistochemistry experiments with the liver tissue showed that the donor-derived cells expressed the markers of both hepatocytes (albumin and cytokeratin-18) and endothelial cells (von Willebrand factor). The results of fluorescent in situ hybridization and immunocytochemistry experiments suggested that differentiation was direct in this model. The BMC-recipient mice expressed FVIII protein and survived in a tail clip challenge experiment. Furthermore, a coagulation assay confirmed that the plasma FVIII activity was maintained at 20.4% (± 3.6%) of normal pooled plasma activity for more than a year without forming its inhibitor. Overall, this report demonstrated that BMCs rescued the bleeding phenotype in hemophilia A mice, suggesting a potential therapy for this and other related disorders.
2D proteome analysis initiates new Insights on the SalmonellaTyphimurium LuxS protein
Authors: Kint Gwendoline , Sonck Kathleen AJ , Schoofs Geert , De Coster David , Vanderleyden Jos , De Keersmaecker Sigrid CJ 
Published: September 2009

Abstract

Background
Quorum sensing is a term describing a bacterial communication system mediated by the production and recognition of small signaling molecules. The LuxS enzyme, catalyzing the synthesis of AI-2, is conserved in a wide diversity of bacteria. AI-2 has therefore been suggested as an interspecies quorum sensing signal. To investigate the role of endogenous AI-2 in protein expression of the Gram-negative pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), we performed a 2D-DIGE proteomics experiment comparing total protein extract of wildtype S. Typhimurium with that of a luxS mutant, unable to produce AI-2.

Results
Differential proteome analysis of wildtype S. Typhimurium versus a luxS mutant revealed relatively few changes beyond the known effect on phase 2 flagellin. However, two highly differentially expressed protein spots with similar molecular weight but differing isoelectric point, were identified as LuxS whereas the S. Typhimurium genome contains only one luxS gene. This observation was further explored and we show that the S. Typhimurium LuxS protein can undergo posttranslational modification at a catalytic cysteine residue. Additionally, by constructing LuxS-βla and LuxS-PhoA fusion proteins, we demonstrate that S. Typhimurium LuxS can substitute the cognate signal peptide sequences of β-lactamase and alkaline phosphatase for translocation across the cytoplasmic membrane in S. Typhimurium. This was further confirmed by fractionation of S. Typhimurium protein extracts, followed by Western blot analysis.

Conclusion
2D-DIGE analysis of a luxS mutant vs. wildtype Salmonella Typhimurium did not reveal new insights into the role of AI-2/LuxS in Salmonella as only a small amount of proteins were differentially expressed. However, subsequent in depth analysis of the LuxS protein itself revealed two interesting features: posttranslational modification and potential translocation across the cytoplasmic membrane. As the S. Typhimurium LuxS protein does not contain obvious signal motifs, it is speculated that LuxS is a new member of so called moonlighting proteins. These observations might have consequences in future studies on AI-2 quorum signaling in S. Typhimurium.
Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study
Authors: Wolf Christiane , Gramer Eugen , Müller-Myhsok Bertram , Pasutto Francesca , Reinthal Eva , Wissinger Bernd , Weisschuh Nicole 
Published: September 2009

Abstract

Background
Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.

Methods
Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.

Results
Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.

Conclusion
Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.
The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey
Authors: Tan Hern Tze , Rahman Rosliza Abdul , Gan Siew Hua , Halim Ahmad Sukari , Hassan Siti Asma' , Sulaiman Siti Amrah , BS Kirnpal-Kaur 
Published: September 2009

Abstract

Background
Antibiotic resistance of bacteria is on the rise, thus the discovery of alternative therapeutic agents is urgently needed. Honey possesses therapeutic potential, including wound healing properties and antimicrobial activity. Although the antimicrobial activity of honey has been effectively established against an extensive spectrum of microorganisms, it differs depending on the type of honey. To date, no extensive studies of the antibacterial properties of tualang (Koompassia excelsa) honey on wound and enteric microorganisms have been conducted. The objectives of this study were to conduct such studies and to compare the antibacterial activity of tualang honey with that of manuka honey.

Methods
Using a broth dilution method, the antibacterial activity of tualang honey against 13 wound and enteric microorganisms was determined; manuka honey was used as the control. Different concentrations of honey [6.25-25% (w/v)] were tested against each type of microorganism. Briefly, two-fold dilutions of honey solutions were tested to determine the minimum inhibitory concentration (MIC) against each type of microorganism, followed by more assays within a narrower dilution range to obtain more precise MIC values. MICs were determined by both visual inspection and spectrophotometric assay at 620 nm. Minimum bactericidal concentration (MBC) also was determined by culturing on blood agar plates.

Results
By visual inspection, the MICs of tualang honey ranged from 8.75% to 25% compared to manuka honey (8.75-20%). Spectrophotometric readings of at least 95% inhibition yielded MIC values ranging between 10% and 25% for both types of honey. The lowest MBC for tualang honey was 20%, whereas that for manuka honey was 11.25% for the microorganisms tested. The lowest MIC value (8.75%) for both types of honey was against Stenotrophomonas maltophilia. Tualang honey had a lower MIC (11.25%) against Acinetobacter baumannii compared to manuka honey (12.5%).

Conclusion
Tualang honey exhibited variable activities against different microorganisms, but they were within the same range as those for manuka honey. This result suggests that tualang honey could potentially be used as an alternative therapeutic agent against certain microorganisms, particularly A. baumannii and S. maltophilia.