bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous Dendritic Cells Combined with Cytokine-Induced Killer Cells Synergize Low-Dose Chemotherapy in Elderly Patients with Acute Myeloid Leukaemia
Authors: Dong M , Liang D , Li Y , Kong D , Kang P , Li K , Ping C , Zhang Y , Zhou X , Zhang Y , Hong L
Published: February 2013

OBJECTIVES: To investigate the possibility of culturing dendritic cells (DCs) and cytokine-induced killer (CIK) cells, obtained at initial diagnosis of AML in elderly patients, and to investigate the safety and efficacy of treatment with autologous DCs and CIK cells when administered to these patients in combination with low-dose chemo therapy. METHODS: DCs and CIK cells obtained at initial diagnosis of AML in elderly patients were cultured and used in combination with low-dose chemo therapy to treat these patients (immunotherapy group). Elderly patients with AML treated only with low-dose chemotherapy served as the control. Before treatment and on day 7 after treatment with autologous DCs and CIK cells, T cell subsets and cytokine levels were evaluated in the immunotherapy group. RESULTS: A total of 21 elderly patients with AML were included in the immunotherapy group and 23 in the control group. The clinical efficacy in the immunotherapy group was greater than in the control group. The percentages of T cell subsets and cytokine levels after immunotherapy treatment were significantly higher than before the treatment. CONCLUSION: Immuno therapy with autologous DCs and CIK cells was found to be a promising candidate for treatment of AML in elderly patients.
The Adipose Tissue Endocrine Mechanism of the Prophylactic Protective Effect of Pioglitazone in High-Fat Diet-Induced Insulin Resistance
Authors: Gong Y , Li J , Li C , Mu Y , Xiao Y , Tian H , Pan C , Liu Y
Published: February 2013

OBJECTIVE: To explore the adipose tissue endocrine mechanism of pioglitazone and its possible prophylactic role in insulin resistance. METHODS: Male Wistar rats were randomized to receive a normal diet (N group), a high-fat insulin resistance-inducing diet (IR group), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken. HepG2 cells were cultured with palmitic acid (PA), pioglitazone and PA plus pioglitazone, and RNA interference was used to downregulate adiponectin receptor (AdipoR) 2 in these cells. The mRNA and protein levels of adipokines (resistin and adiponectin), AdipoR1 and 2 and uptake of [3H]-labelled glucose were measured in the HepG2 cells. RESULTS: Resistin and adiponectin in adipose tissue and AdipoR2 in liver tissue were significantly decreased in the IR group compared with the N group. Adiponectin and AdipoR2 were significantly increased and insulin resistance significantly decreased in the P group versus the IR group. In HepG2 cells, AdipoR2 levels and glucose uptake decreased significantly when PA was ≥ 200 μM, but were elevated by pioglitazone. Small interfering RNA-AdipoR2 confirmed glucose uptake in liver was regulated by AdipoR2. CONCLUSIONS: Pioglitazone prevented insulin resistance in rats fed a high-fat diet. Liver AdipoR2-mediated glucose uptake is important in the prophylactic effect of pioglitazone on insulin resistance.
Autologous Platelet-Rich Clot Releasate Stimulates Proliferation and Inhibits Differentiation of Adult Rat Tendon Stem Cells towards Nontenocyte Lineages
Authors: Chen L , Dong S-W , Tao X , Liu J-P , Tang K-L , Xu J-Z
Published: February 2013

OBJECTIVE: To explore the effects of autologous platelet-rich clot releasate (PRCR) on proliferation and differentiation of adult rat tendon stem cells (TSCs) in vitro, following intense mechanical stretching. METHODS: TSCs were subjected to 8% mechanical stretching and subsequently incubated in control medium or medium supplemented with 2% or 10% PRCR. Collagen types I and III, peroxisome proliferator-activated receptor-γ (PPARγ), sex determining region Y-box 9 (SOX-9) and runt-related transcription factor 2 (RUNX2) concentrations were assessed via Western blotting and flow cytometry. Transforming growth factor (TGF)-β1 and vascular endothelial growth factor concentrations were measured using enzyme-linked immunosorbent assay. Treated TSCs were also cultured in adipogenic, chondrogenic or osteogenic culture media. RESULTS: PRCR increased the number of TSCs, and the concentrations of collagen types I and III and TGF-β1. In contrast, PRCR significantly reduced PPARγ, SOX-9 and RUNX2-positive cell numbers, and significantly reduced the numbers of TSC-derived adipocytes, chondrocytes and osteocytes. CONCLUSION: PRCR induced tenocyte differentiation while suppressing the adipocyte, chondrocyte and osteocyte lineages believed to impede tendon healing.
Modification of the Neurotrophin-3 Gene Promotes Cholinergic Neuronal Differentiation and Survival of Neural Stem Cells Derived from Rat Embryonic Spinal Cord In Vitro and In Vivo
Authors: Lin S , Wang Y , Zhang C , Xu J
Published: February 2013

OBJECTIVE: To investigate the effects of the neurotrophin-3 ( NTF3) gene on the survival and differentiation of neural stem cells (NSCs) in vitro and in vivo. METHODS: The NTF3 gene was isolated from rats, amplified by polymerase chain reaction (PCR) and subcloned into the lentiviral vector pWPXL-MOD to construct a lentiviral expression vector pWPXL-MOD— NTF3. Reverse transcription—PCR and Western blotting were used to analyse NTF3 mRNA and protein levels, respectively. Adult rats with sectioned tibial nerves received implants of NSCs transfected with either pWPXL-MOD— NTF3 ( n = 30) or an empty expression vector ( n = 30). In vitro and in vivo cell differentiation and survival were determined by fluorescence immunohistochemistry. RESULTS: Expression of NTF3 significantly increased the differentiation of NSCs into cholinergic neurons both in vitro and in vivo. NTF3-expressing NSCs implanted into the tibial nerve also survived longer than cells without NTF3 gene modification. CONCLUSIONS: The NTF3 gene promoted differentiation of NSCs into cholinergic neurons and enhanced neuronal cell survival. These findings may have clinical implications for cell transplantation therapy in patients with nerve injury.
Target-Controlled Infusion of Remifentanil for Laryngeal Mask Airway Insertion during Sevoflurane Induction in Adults
Authors: Kwak Hj , Chae Yj , Lee Kc , Kim Jy
Published: February 2013

OBJECTIVE: This randomized, double-blind study investigated the suitable target effect-site concentration of remifentanil for laryngeal mask airway (LMA) insertion during inhalation induction with sevoflurane. METHODS: Patients aged 18 – 60 years were randomly assigned to one of three groups receiving infusions of normal saline (control group), or infusions with target effect-site remifentanil concentrations of either 1 ng/ml (R1 group) or 2 ng/ml (R2 group), 1 min after the induction of anaesthesia with sevoflurane. LMA insertion was attempted 2 min after induction. Insertion conditions were graded using a six-variable, three-point scale (excellent, intermediate or poor). RESULTS: A total of 102 patients were included. The proportion of patients ranked as excellent for the LMA insertion was significantly higher in groups R1 and R2 compared with the control group. The incidence of apnoea was significantly more frequent in the R2 group than in the control or R1 groups. CONCLUSIONS: Compared with 1 ng/ml remifentanil or normal saline, target-controlled infusion of 2 ng/ml remifentanil significantly improved the LMA insertion conditions during sevoflurane inhalational induction, although apnoeic episodes were more frequently observed.
Comparison of Desflurane and Sevoflurane Anaesthesia in Relation to the Risk of Vagally Mediated Reflex Bradycardia during Gastrectomy
Authors: Joo Y , Shin B-S , Cho E-A , Kim D-K
Published: February 2013

OBJECTIVE: This study compared the risk of clinically significant reflex bradycardia during anaesthesia with sevoflurane or desflurane in patients undergoing gastrectomy. METHODS: In this randomized prospective study, 100 patients undergoing gastrectomy were assigned to receive sevoflurane ( n = 50) or desflurane ( n = 50) anaesthesia. No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to < 50 beats/min, or a decrease to 50 – 59 beats/min if associated with a systolic arterial pressure of ≤ 70 mmHg in response to surgical manoeuvres. If reflex bradycardia developed, atropine or ephedrine were administered according to a predefined treatment protocol. RESULTS: Data from 85 patients were available for analysis. The proportion of patients with symptomatic reflex bradycardia in the sevoflurane and desflurane groups was similar (69.0% versus 55.8%, respectively) and both groups required a similar amount of atropine and/or ephedrine. CONCLUSIONS: Clinically significant reflex bradycardia occurred with a relatively high frequency during gastrectomy. Although desflurane is associated with sympathetic activation, it did not provide a protective effect against vagally mediated reflex bradycardia during gastrectomy compared with sevoflurane.
Plasma Adrenomedullin and Subclinical Cardiorenal Syndrome in Patients with Type 2 Diabetes Mellitus
Authors: Pecková M , Charvat J , Schuck O , Zamrazil V , Bilek R , Hill M , Svab P , Horackova M
Published: February 2013

OBJECTIVE: To evaluate whether plasma adrenomedullin is involved in the previously reported significant inverse correlation between left ventricular (LV) end-diastolic pressure (peak velocity of early transmitral flow/peak velocity of early diastolic mitral annular motion ratio [E/E′]) and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus, mild-to-moderate renal function impairment and LV relaxation impairment (E′ ≤ 7.1 cm/s). METHODS: Plasma adrenomedullin concentration, E/E′ and eGFR were assessed in 82 patients with type 2 diabetes. RESULTS: Plasma adrenomedullin concentration was positively correlated with eGFR in patients with or without LV relaxation impairment, and inversely correlated with E/E′ in patients with LV relaxation impairment. Multivariate linear regression analysis supported a role for plasma adrenomedullin in the association between E/E′ and eGFR. CONCLUSION: These results support the hypothesis that adrenomedullin modulates the interaction between the heart and kidneys in early subclinical cardiorenal syndrome in patients with type 2 diabetes mellitus.
A Morphological Study of the Left Atrial Appendage in Chinese Patients with Atrial Fibrillation
Authors: Shi A-W , Chen M-L , Yang B , Cao K-J , Kong X-Q
Published: February 2013

OBJECTIVE: Using angiography, this study examined left atrial appendage (LAA) morphology in Chinese patients with atrial fibrillation (AF) or congenital atrial septal defects (ASD), to provide data that might aid the design of new LAA-occluding devices to prevent cardioembolism and stroke in patients with AF. METHODS: Patients with AF or ASD were enrolled. The LAA was visualized angiographically; its dimensions were measured and the emptying fraction was calculated. RESULTS: A total of 45 patients with AF and 30 patients with ASD were included in the study. LAA morphology was classified into eight categories. The majority of patients with AF had tube-shaped LAAs with a single lobe; the most common LAA morphologies in patients with ASD were irregular or sphere-like, with multiple lobes. Patients with AF had significantly larger LAAs with significantly lower emptying fractions compared with LAAs of patients with ASD. CONCLUSIONS: The LAA demonstrated considerable morphological variability in terms of its size, shape and number of lobes. The design of new occluding devices must take into account the size and shape of the LAA in patients with AF.
Clinical Analysis of 50 Chinese Patients with Aqueous Misdirection Syndrome: A Retrospective Hospital-Based Study
Authors: Zhou C , Qian S , Yao J , Tang Y , Qian J , Lu Y , Xu G , Sun X
Published: February 2013

OBJECTIVES: To evaluate the efficacy of treatments for aqueous misdirection syndrome and explore possible risk factors influencing prognosis. METHODS: Data including demographics, initial clinical characteristics and ocular outcomes at follow-up were collected for patients treated for aqueous misdirection syndrome. Main outcome measures were: best-corrected visual acuity (BCVA); intraocular pressure (IOP); number of antiglaucoma medications; recurrence; complications. RESULTS: Data were available for 50 patients (57 eyes). Final mean BCVA improved significantly and correlated with baseline BCVA (mean follow-up, 34.47 ± 28.65 months). Final mean IOP and mean number of antiglaucoma medications were significantly reduced. Treatment failure rates were higher in patients with significantly higher IOP at baseline and/or shorter axial length. Following pars plana vitrectomy (PPV), recurrence occurred in two of 10 pseudophakic and one of 40 phakic eyes; complications were observed in 12/50 eyes (choroidal detachment, corneal decompensation, retinal detachment, vitreous haemorrhage, hyphaema). CONCLUSIONS: PPV and laser treatments, augmented by pharmacotherapy, were effective in treating aqueous misdirection syndrome. Surgical intervention should be undertaken early in eyes with higher baseline IOP and/or shorter axial length. Total vitrectomy— zonulectomy—iridectomy is a potential approach for recalcitrant cases.
The Characterization and Management of Castleman's Disease
Authors: Zhou N , Huang Cw , Huang C , Liao W
Published: February 2013

OBJECTIVE: Castleman's disease (CD) is a rare disorder of unknown aetiology characterized by lymph node enlargement. This study evaluated the clinical features, diagnosis and outcomes of surgical treatment in patients with CD. METHODS: The medical records of 10 patients with histologically confirmed CD who underwent surgery between 2003 and 2008 were retrospectively reviewed. Study endpoints were survival and recurrence. RESULTS: The age of disease onset ranged from 11 to 63 years (median 38 years). Of the 10 patients included in the study, eight were diagnosed with localized (unicentric) CD and two with multicentric CD. All eight patients with localized (unicentric) CD were asymptomatic. Histological evidence indicated the hyaline vascular form of CD in eight patients and the plasmacytic form in the remaining two patients. The primary treatment was complete surgical resection in nine cases, and these patients were alive with no evidence of recurrence or exacerbation at the time of writing (June 2011). CONCLUSIONS: Localized (unicentric) CD is usually of the hyaline vascular form and complete surgical excision of the tumour allows full recovery in most cases.
Laparoscopic versus Open Surgery for Rectal Cancer: A Clinical Comparative Study
Authors: Li Z , Ying X , Shen Y , Ye P , Pan W , Chen H
Published: February 2013

OBJECTIVE: To compare short-term surgical outcomes and long-term survival following laparoscopic or open resection for rectal cancer. METHODS: A total of 381 patients undergoing laparoscopic surgery and 276 undergoing open surgery for curative resection of rectal cancer were included. Long-term survival and peri- and postoperative data were retrospectively reviewed from a prospectively-collected database. RESULTS: Surgical groups were comparable regarding age, gender, tumour stage and preoperative comorbidities. Laparascopic surgery was associated with significantly longer duration of surgery, less intraoperative blood loss and fewer postoperative infections than open surgery. Patients who underwent laparoscopic resection had significantly earlier recovery of gastrointestinal function than those who underwent open surgery. There were no significant between-group differences in number of lymph nodes excised, specimen length or distal margin. The 3- and 5-year survival rates and overall survival were similar in the two groups, and survival was not influenced by tumour location. CONCLUSION: Laparoscopic surgery can achieve the same oncological results as open resection in patients with rectal cancer, supporting its continued use in the management of this disease.
A new approach to interactive viewpoint selection for volume data sets
Authors: Kim Han Suk , Unat Didem , Baden Scott B , Schulze Jürgen P
Published: February 2013

Automatic viewpoint selection algorithms try to optimize the view of a data set to best show its features. They are often based on information theoretic frameworks. Although many algorithms have shown useful results, they often take several seconds to produce a result because they render the scene from a variety of viewpoints and analyze the result. In this article, we propose a new algorithm for volume data sets that dramatically reduces the running time. Our entire algorithm takes less than a second, which allows it to be integrated into real-time volume-rendering applications. The interactive performance is achieved by solving a maximization problem with a small sample of the data set, instead of rendering it from a variety of directions. We compare performance results of our algorithm to state-of-the-art approaches and show that our algorithm achieves comparable results for the resulting viewpoints. Furthermore, we apply our algorithm to multichannel volume data sets.
The relationship of trigger finger and flexor tendon volar migration after carpal tunnel release
Authors: Lee S. K. , Bae K. W. , Choy W. S.
Published: February 2013

It has been suggested that the increased frequency of trigger finger (TF) after carpal tunnel release (CTR) may be caused by the volar migration of the flexor tendons at the wrist altering the tendon biomechanics at the A1 pulley. This hypothesis has not been validated. We performed pre- and post-operative ultrasonography (USG) on the affected wrists of 92 patients who underwent CTR. Pre-operative USG was performed in neutral with no tendon loading; post-operative USG was performed in neutral unloaded and in various positions of wrist flexion whilst loading the flexor tendons with gripping.

The mean volar migration of the flexor tendons after CTR was 2.2 (SD 0.4) mm in the unloaded neutral position. It was 1.8 (SD 0.4) mm in patients who did not develop TF and 2.5 (SD 0.5) mm in those who did ( p = 0.0067). In loaded wrist flexion, the mean volar migration of flexor tendons after CTR in patients who did not develop TF and those who did was 2.1 and 3.0 mm in 0° flexion; 3.2 and 3.9 mm in 15° flexion; 4.3 and 5.1 mm in 30° flexion; and 4.9 and 5.8 mm in 45° flexion, respectively. There were significant differences between patients with and without TF at each flexion angle.

Our data indicate that patients with greater volar migration of the flexor tendons after CTR are more likely to develop TF. This conclusion supports the hypothesis that the occurrence of TF after CTR may be caused by the bowstringing effects of the flexor tendons.
Lisfranc Injury in a West Point Cadet
Authors: Diebal Angela R. , Westrick Richard B. , Alitz Curtis , Gerber J. Parry
Published: February 2013

Background:

Lisfranc joint injuries are fairly uncommon; however, few injuries hold such an elevated potential for devastating chronic secondary pain and disability. It is imperative when evaluating an injury to the ankle or foot to have a high clinical index of suspicion for Lisfranc injury, as physical examination findings are often subtle.

Case Description:

An 18-year-old military cadet reported to a direct-access sports physical therapy clinic with foot pain. Despite negative radiographic findings, there was a high suspicion for Lisfranc injury based on the injury mechanism and physical examination. A computed tomography scan demonstrated an oblique fracture through the base of the third metatarsal, a small marginal fracture at the plantar base of the second metatarsal, and a subtle diastasis. Two days following his injury, he underwent an open reduction and internal fixation, completed subsequent rehabilitation, and returned to full activity approximately 1 year following injury.

Conclusion:

Early diagnosis of Lisfranc injuries is imperative for proper management and prevention of a poor functional outcome. If a strong clinical suspicion exists, negative radiographic findings are insufficient to rule out a Lisfranc injury, and therefore, advanced imaging is required.
Drug-Induced Lupus Associated with Rifabutin
Authors: Anyimadu Henry , Saadia Naseem , Mannheimer Sharon
Published: February 2013

Drug-induced lupus (DIL) is a rare adverse reaction to medications with features resembling idiopathic systemic lupus erythromatosis. Rifabutin/rifamycins have only rarely been reported as a cause of DIL, and no cases have been reported in blacks. A 55-year-old African American woman with HIV presented with severe generalized arthralgias and recurrent oral ulcers while receiving treatment for tuberculous meningitis. Arthralgias, which began in her knees after 5 weeks of antituberculous therapy, progressed to involve the joints in the ankles, wrists, and hands. She had no associated fever or rash. When she had these symptoms her antinuclear antibody (ANA) was 1:1280 homogenous pattern, antidouble stranded DNA was negative, antihistone antibody was strongly positive, anti-smith and antiribonucleoprotein (anti-RNP) were negative. Her symptoms resolved within 2 months of stopping rifabutin while continuing other antituberculous medications and her ANA titer started to decrease. We review the existing literature on this subject.
Salmonella Spinal Infection
Authors: Berngard Samuel Clark , Miller Marshall
Published: February 2013

We present an unusual case of nontyphoidal Salmonella causing an epidural abscess and vertebral osteomyelitis in a severely immunocompromised patient with AIDS as well as a review of the literature. Salmonella vertebral osteomyelitis is exceptionally rare, and this is the first case report in a patient with AIDS.
Foxp3+ T-regulatory cells require DNA methyltransferase 1 expression to prevent development of lethal autoimmunity
Authors: Wang Liqing , Liu Yujie , Beier Ulf H. , Han Rongxiang , Bhatti Tricia R. , Akimova Tatiana , Hancock Wayne W.
Published: February 2013

Key Points

Foxp3 expression is increased by DNMT inhibitors and may have potential utility in efforts to develop Foxp3+ Tregs for cellular therapy. Dnmt1 deletion impairs Treg function and results in lethal autoimmunity, such that use of Dnmt inhibitors may warrant careful consideration.
PDK1 regulates platelet activation and arterial thrombosis
Authors: Chen Xue , Zhang Yue , Wang Yanhua , Li Ding , Zhang Lin , Wang Kemin , Luo Xinping , Yang Zhongzhou , Wu Yi , Liu Junling
Published: February 2013

Key Points

PDK1 is involved in thrombin-induced platelet activation and αIIbβ3-mediated outside-in signaling by regulating the downstream effector Gsk3β.
EB1, p150Glued, and Clasp1 control endothelial tubulogenesis through microtubule assembly, acetylation, and apical polarization
Authors: Kim Dae Joong , Martinez-Lemus Luis A. , Davis George E.
Published: February 2013

Key Points

Microtubule tip complex proteins control EC lumen formation through tubulin acetylation to support the developing apical membrane surface. Microtubule assembly and tubulin modifications interface with proteolytic and kinase cascades to control EC lumen formation in 3D matrices.
Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma
Authors: Ouyang Jing , Plütschow Annette , von Strandmann Elke Pogge , Reiners Katrin S. , Ponader Sabine , Rabinovich Gabriel A. , Neuberg Donna , Engert Andreas , Shipp Margaret A.
Published: February 2013

Key Points

Serum levels of galectin-1 are significantly higher in patients with cHL than in normal controls. Galectin-1 serum levels are associated with clinical parameters of tumor burden in patients with cHL.
Nearly n-homomorphisms and n-derivations in fuzzy ternary Banach algebras
Authors: Hassani Feysal , Ebadian Ali , Eshaghi Gordji Madjid , Azadi Kenary Hassan
Published: February 2013

Let

n
=
3
k
+
2

for some

k
∈
N

. We investigate the generalized Hyers-Ulam stability of n-homomorphisms and n-derivations on fuzzy ternary Banach algebras related to the generalized Cauchy-Jensen additive functional equation.

MSC:39B52, 46S40, 26E50.
Management of stage II colon cancer - the use of molecular biomarkers for adjuvant therapy decision
Authors: Donada Marisa , Bonin Serena , Barbazza Renzo , Pettirosso Daniel , Stanta Giorgio
Published: February 2013

Background

There is uncertainty on the benefit of adjuvant chemotherapy in patients with stage II colorectal cancers. The aim of this study is to investigate the combined role of clinical, pathological and molecular parameters to identify those stage II patients who better benefit from adjuvant therapy.

Methods

We examined 120 stage II colon cancer patients. Of these, 60 patients received adjuvant 5-FU chemotherapy after surgery and the other 60 did not receive therapy. Immunohistochemical (IHC) analyses were performed to evaluate the expressions of Thymidylate synthetase (TYMS), TP53 (p53), β-catenin (CTNNB1) and CD8. For TYMS, its mRNA expression levels were also investigated by real time qRT-PCR. The entire case study was characterized by the presence of a defect in the MMR (mismatch repair) system, the presence of the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRAF gene. At the histo-pathological level, the depth of tumour invasion, lymphovascular invasion, invasion of large veins, host lymphocytic response and tumour border configuration were recorded.

Results

The presence of the V600E mutation in the BRAF gene was a poor prognostic factor for disease free and overall survival (DFS; hazard ratio [HR], 2.57; 95% CI: 1.03 -6.37; p = 0.04 and OS; HR, 3.68; 95% CI: 1.43-9.47; p < 0.01 respectively), independently of 5-FU treatment. Adjuvant therapy significantly improved survival in patients with high TYMS levels (p = 0.04), while patients with low TYMS had a better outcome if treated by surgery alone (DFS; HR, 6.07; 95% CI, 0.82 to 44.89; p = 0.04). In patients with a defect in the MMR system (dMMR), 5-FU therapy was associated to reduced survival (DFS; HR, 37.98; 95% CI, 1.04 to 1381.31; p = 0.04), while it was beneficial for CIMP-High associated tumours (DFS; HR, 0.17; 95% CI, 0.02 to 1.13; p = 0.05).

Conclusions

Patients’ characterization according to MMR status, CIMP phenotype and TYMS mRNA expression may provide a more tailored approach for adjuvant therapy in stage II colon cancer.
Spread of Influenza A(H1N1) oseltamivir-resistant viruses in Africa in 2008 confirmed by multiple introductions in Senegal
Authors: Dia Ndongo , Niang Mbayame N , Diadhiou Saadiya A , Goudiaby Déborah G , Faye Abdourahmane , Kiori Davy , Bâ Mady , Michel Rémy , Diop Ousmane M
Published: February 2013

Background

Among Influenza neuraminidase inhibitors (NAIs), oseltamivir corresponds to the most widely used agent to treat influenza disease. However since 2001, several cases of resistance to NAIs have been reported for circulating seasonal A(H1N1) Influenza viruses. A direct resistance mechanism may be invoked, involving critical mutations in the viral NA gene that prevent the drug binding to its target. Same phenomenon is reported for adamantanes drugs and mutations in the M2 channel protein gene of Influenza viruses.

Methods

Reverse-Transcription/Restriction Fragment Length Polymorphism (RT-PCR/RFLP) method, phenotypic testing for oseltamivir resistance, and sequencing of NA, HA and M2 genes were used in this study. Phylogenetic analyses were performed using BioEdit and Mega 5 softwares for alignment of sequences and phylogenetic trees building respectively.

Results

Using a simple RT-PCR/RFLP method, we found that the 86 seasonal A(H1N1) isolates from 2008 bear the oseltamivir resistance-associated mutation (H274Y) in the NA gene. In contrast all isolates isolated in Senegal in 2007 were sensitive to oseltamivir. These results were first confirmed by finding high IC50 values using a phenotypic testing for oseltamivir resistance, and secondly by sequencing the whole NA gene. Regarding M2 gene, no mutation associated to adamantanes resistance was characterized of the isolates.

Conclusions

The present work provides evidence of circulation of drug-resistant seasonal A(H1N1) viruses during the 2008 influenza season (July to September) in Senegal. The results are in favor of multiple introductions of oseltamivir resistant viruses (ORV) A(H1N1) in Senegal.

Phylogenetic analyses of isolates with complete sequences of N1 and HA1 genes showed that they belong to clade 2B and suggest sequential introductions in Africa.
Sugary food and beverage consumption and epithelial ovarian cancer risk: a population-based case–control study
Authors: King Melony G , Olson Sara H , Paddock Lisa , Chandran Urmila , Demissie Kitaw , Lu Shou-En , Parekh Niyati , Rodriguez-Rodriguez Lorna , Bandera Elisa V
Published: February 2013

Background

Ovarian cancer is the deadliest gynecologic cancer in the US. The consumption of refined sugars has increased dramatically over the past few decades, accounting for almost 15% of total energy intake. Yet, there is limited evidence on how sugar consumption affects ovarian cancer risk.

Methods

We evaluated ovarian cancer risk in relation to sugary foods and beverages, and total and added sugar intakes in a population-based case–control study. Cases were women with newly diagnosed epithelial ovarian cancer, older than 21 years, able to speak English or Spanish, and residents of six counties in New Jersey. Controls met same criteria as cases, but were ineligible if they had both ovaries removed. A total of 205 cases and 390 controls completed a phone interview, food frequency questionnaire, and self-recorded waist and hip measurements. Based on dietary data, we computed the number of servings of dessert foods, non-dessert foods, sugary drinks and total sugary foods and drinks for each participant. Total and added sugar intakes (grams/day) were also calculated. Multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for food and drink groups and total and added sugar intakes, while adjusting for major risk factors.

Results

We did not find evidence of an association between consumption of sugary foods and beverages and risk, although there was a suggestion of increased risk associated with sugary drink intake (servings per 1,000 kcal; OR=1.63, 95% CI: 0.94-2.83).

Conclusions

Overall, we found little indication that sugar intake played a major role on ovarian cancer development.
3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing
Authors: Longati Paola , Jia Xiaohui , Eimer Johannes , Wagman Annika , Witt Michael-Robin , Rehnmark Stefan , Verbeke Caroline , Toftgård Rune , Löhr Matthias , Heuchel Rainer L
Published: February 2013

Background

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance.

Methods

Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine.

Results

Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect.

Conclusions

We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.
Photoprotective and antioxidant effects of Rhubarb: inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes
Authors: Silveira Jéssica PS , Seito Leonardo N , Eberlin Samara , Dieamant Gustavo C , Nogueira Cecília , Pereda Maria CV , Di Stasi Luiz C
Published: February 2013

Background

Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes.

Methods

The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method.

Results

Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation.

Conclusions

These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage.
Predicting out of intensive care unit cardiopulmonary arrest or death using electronic medical record data
Authors: Alvarez Carlos A , Clark Christopher A , Zhang Song , Halm Ethan A , Shannon John J , Girod Carlos E , Cooper Lauren , Amarasingham Ruben
Published: February 2013

Background

Accurate, timely and automated identification of patients at high risk for severe clinical deterioration using readily available clinical information in the electronic medical record (EMR) could inform health systems to target scarce resources and save lives.

Methods

We identified 7,466 patients admitted to a large, public, urban academic hospital between May 2009 and March 2010. An automated clinical prediction model for out of intensive care unit (ICU) cardiopulmonary arrest and unexpected death was created in the derivation sample (50% randomly selected from total cohort) using multivariable logistic regression. The automated model was then validated in the remaining 50% from the total cohort (validation sample). The primary outcome was a composite of resuscitation events, and death (RED). RED included cardiopulmonary arrest, acute respiratory compromise and unexpected death. Predictors were measured using data from the previous 24 hours. Candidate variables included vital signs, laboratory data, physician orders, medications, floor assignment, and the Modified Early Warning Score (MEWS), among other treatment variables.

Results

RED rates were 1.2% of patient-days for the total cohort. Fourteen variables were independent predictors of RED and included age, oxygenation, diastolic blood pressure, arterial blood gas and laboratory values, emergent orders, and assignment to a high risk floor. The automated model had excellent discrimination (c-statistic=0.85) and calibration and was more sensitive (51.6% and 42.2%) and specific (94.3% and 91.3%) than the MEWS alone. The automated model predicted RED 15.9 hours before they occurred and earlier than Rapid Response Team (RRT) activation (5.7 hours prior to an event, p=0.003)

Conclusion

An automated model harnessing EMR data offers great potential for identifying RED and was superior to both a prior risk model and the human judgment-driven RRT.
Why and how protein aggregation has to be studied in vivo
Authors: Ami Diletta , Natalello Antonino , Lotti Marina , Doglia Silvia Maria
Published: February 2013

The understanding of protein aggregation is a central issue in different fields of protein science, from the heterologous protein production in biotechnology to amyloid aggregation in several neurodegenerative and systemic diseases. To this goal, it became more and more evident the crucial relevance of studying protein aggregation in the complex cellular environment, since it allows to take into account the cellular components affecting protein aggregation, such as chaperones, proteases, and molecular crowding. Here, we discuss the use of several biochemical and biophysical approaches that can be employed to monitor protein aggregation within intact cells, focusing in particular on bacteria that are widely employed as microbial cell factories.
Diversity of the var gene family of Indonesian Plasmodium falciparum isolates
Authors: Sulistyaningsih Erma , Fitri Loeki E , Löscher Thomas , Berens-Riha Nicole
Published: February 2013

Background

The large polymorphic protein PfEMP1 is encoded by the var gene family. PfEMP1 has been shown to play an important role as cytoadherence ligand on the surface of infected erythrocytes and thereby contributes to the distinct pathogenesis of malaria. The study explored the diversity of the DBL1α and DBL2β-C2 domains of the protein from Indonesian Plasmodium falciparum field isolates.

Methods

Samples of patients with severe and uncomplicated malaria from two different malaria-endemic areas in Indonesia were collected and DNA directly extracted. Dried blood on filter paper was prepared for RNA extraction. PCR amplicons were either cloned and subsequently sequenced or directly sequenced for analysis on nucleotide and amino acid level. Recently published as well as self-designed primers were used for amplification.

Results

Blood from eight patients was finally used for analysis. Seventy-one different sequences out of over 500 DBL1α sequenced clones were observed, resulting in an average of 8.9 different DBL1α sequences per isolate. The average DBL1α sequence similarity within isolates was similar to between isolates. Phylogenetic analysis demonstrated no clustering of sequences regarding strain or geographical origin. The DBL1α sequences were analysed by distribution of semi-conserved features (cysteine/PoLV1-4 grouping) and classified into six sequence groups. The DBL1α cys2 type was observed in all expressed sequences in vivo. Expression of certain DBL sequences implied potential involvement in the pathogenesis. As expected, the DBL2β-C2 domains showed high to moderate homology among each other.

Conclusion

The DBL1α domains of PfEMP1 from clinical Indonesian isolates showed high divergence among same isolates and some similarities with other Asia-Pacific strains. Further investigations of important var gene domains with a larger sample size are required to confirm with statistical significance observed associations with severe malaria in Indonesian samples.
Fabrication and characterization of La2Zr2O7 films on different buffer architectures for YBa2Cu3O7−δ coated conductors by RF magnetron sputtering
Authors: Xu Da , Liu Linfei , Xiao Guina , Li Yijie
Published: February 2013

La2Zr2O7 (LZO) films were grown on different buffer architectures by radio frequency magnetron sputtering for the large-scale application of YBa2Cu3O7−x
(YBCO)-coated conductors. The three different buffer architectures were cerium oxide (CeO2), yttria-stabilized zirconia (YSZ)/CeO2, and CeO2/YSZ/CeO2. The microstructure and surface morphology of the LZO film were studied by X-ray diffraction, optical microscopy, field emission scanning electron microscopy, and atomic force microscopy. The LZO films prepared on the CeO2, YSZ/CeO2, and CeO2/YSZ/CeO2 buffer architectures were preferentially c-axis-oriented and highly textured. The in-plane texture of LZO film on CeO2 single-buffer architecture was ∆ φ = 5.5° and the out-of-plane texture was ∆ ω = 3.4°. All the LZO films had very smooth surfaces, but LZO films grown on YSZ/CeO2 and CeO2/YSZ/CeO2 buffer architectures had cracks. The highly textured LZO film grown on CeO2-seed buffered NiW tape was suitable for the epitaxial growth of YBCO film with high currents.
Effects of the electrical conductivity and orientation of silicon substrate on the synthesis of multi-walled carbon nanotubes by thermal chemical vapor deposition
Authors: Choi Hyonkwang , Gong Jaeseok , Lim Yeongjin , Im Ki Hong , Jeon Minhyon
Published: February 2013

We studied the effects of the electrical conductivity and orientation of silicon substrate on both catalytic Fe thin film and the structure and morphology of multi-walled carbon nanotube (MWNT) grown by low-pressure chemical vapor deposition. Both p-type Si(100) and Si(111) substrates with three different doping concentrations (high, low, undoped) were used to evaluate the formation of catalytic nanoparticles and the growth of MWNTs. The morphology of catalytic nanoparticles such as size and density was characterized by field-emission scanning electron microscopy, Cs-corrected energy-filtered transmission electron microscopy, and X-ray photoelectron spectroscopy. Structural characteristics of MWNTs grown on different combinations of silicon substrate orientation and electrical conductivities (σ) were also systematically analyzed. Based on the experimental results, growth modes of MWNTs could be controlled by choosing an appropriate combination of σ and orientation of Si substrates.
Estimating HIV prevalence from surveys with low individual consent rates: annealing individual and pooled samples
Authors: Hund Lauren , Pagano Marcello
Published: February 2013

Many HIV prevalence surveys are plagued by the problem that a sizeable number of surveyed individuals do not consent to contribute blood samples for testing. One can ignore this problem, as is often done, but the resultant bias can be of sufficient magnitude to invalidate the results of the survey, especially if the number of non-responders is high and the reason for refusing to participate is related to the individual’s HIV status. One reason for refusing to participate may be for reasons of privacy. For those individuals, we suggest offering the option of being tested in a pool. This form of testing is less certain than individual testing, but, if it convinces more people to submit to testing, it should reduce the potential for bias and give a cleaner answer to the question of prevalence. This paper explores the logistics of implementing a combined individual and pooled testing approach and evaluates the analytical advantages to such a combined testing strategy. We quantify improvements in a prevalence estimator based on this combined testing strategy, relative to an individual testing only approach and a pooled testing only approach. Minimizing non-response is key for reducing bias, and, if pooled testing assuages privacy concerns, offering a pooled testing strategy has the potential to substantially improve HIV prevalence estimates.
Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman
Authors: Guan Zhi-Wei , Sun Lu , Wang Yan-Qiu , Xu Bai-Xuan
Published: February 2013

Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results. Recurrence or metastasis was not found after 14 months of follow-up.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4264758678755142
Differentiated embryonic chondrocyte-expressed gene 1 is associated with hypoxia-inducible factor 1α and Ki67 in human gastric cancer
Authors: Jia Yan-Fei , Xiao Dong-Jie , Ma Xiao-Li , Song Yan-Yan , Hu Rui , Kong Yi , Zheng Yan , Han Shu-Yi , Hong Ruan-Li , Wang Yun-Shan
Published: February 2013

Background

Gastric cancer is a leading causes of cancer-related deaths ,but the underlying molecular mechanisms of its progression are largely unknown. Differentiated embryonic chondrocyte-expressed gene 1 (DEC1), is an important transcription factor involved in the progression of tumors and has recently been identified to be strongly inducible by hypoxia. Little is known about the contribution of DEC1 to the intracellular hypoxia and proliferation signaling events in gastric cancer.

Methods

Immunohistochemistry was used to detect the expression of DEC1, hypoxia-inducible factor 1(HIF-1α) and Ki67 in 173 human gastric cancer samples and adjacent non-tumor tissues samples. The relationship between DEC1, HIF-1α and Ki67 was evaluated.

Results

DEC1 protein was persistently expressed in the nucleus and cytoplasm of gastric cancer tissue. The protein expression of DEC1 and HIF-1α in tumour tissues was 83.8% and 54.3%, respectively, and was significantly higher than that in adjacent normal tissues (83.8% vs 23.7%, P <0.001; 54.3% vs 12.7%, P< 0.001). The expression of DEC1 and HIF-1α was associated with poor histological differentiation. (P < 0. 01). Furthermore, DEC1 level was positively correlated with HIF-1α (P < 0. 01, r=0.290) and Ki67 expression (P < 0. 01, r=0.249).

Conclusion

The upregulation of DEC1 may play an important role in hypoxia regulation and cell proliferation in gastric cancer. The relevant molecular mechanism requires further investigation.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1794565980889391