bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two non-bronchoscopic methods for evaluating inflammation in patients with acute hypoxaemic respiratory failure
Authors: Colucci Giuseppe , Domenighetti Guido , Della Bruna Roberto , Bonilla Josè , Limoni Costanzo , Matthay Michael A , Martin Thomas R
Published: August 2009

Introduction

The simple bedside method for sampling undiluted distal pulmonary edema fluid through a normal suction catheter (s-Cath) has been experimentally and clinically validated. However, there are no data comparing non-bronchoscopic bronchoalveolar lavage (mini-BAL) and s-Cath for assessing lung inflammation in acute hypoxaemic respiratory failure. We designed a prospective study in two groups of patients, those with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and those with acute cardiogenic lung edema (ACLE), designed to investigate the clinical feasibility of these techniques and to evaluate inflammation in both groups using undiluted sampling obtained by s-Cath. To test the interchangeability of the two methods in the same patient for studying the inflammation response, we further compared mini-BAL and s-Cath for agreement of protein concentration and percentage of polymorphonuclear cells (PMNs).

Methods

Mini-BAL and s-Cath sampling was assessed in 30 mechanically ventilated patients, 21 with ALI/ARDS and 9 with ACLE. To analyse agreement between the two sampling techniques, we considered only simultaneously collected mini-BAL and s-Cath paired samples. The protein concentration and polymorphonuclear cell (PMN) count comparisons were performed using undiluted sampling. Bland-Altman plots were used for assessing the mean bias and the limits of agreement between the two sampling techniques; comparison between groups was performed by using the non-parametric Mann-Whitney-U test; continuous variables were compared by using the Student t-test, Wilcoxon signed rank test, analysis of variance or Student-Newman-Keuls test; and categorical variables were compared by using chi-square analysis or Fisher exact test.

Results

Using protein content and PMN percentage as parameters, we identified substantial variations between the two sampling techniques. When the protein concentration in the lung was high, the s-Cath was a more sensitive method; by contrast, as inflammation increased, both methods provided similar estimates of neutrophil percentages in the lung. The patients with ACLE showed an increased PMN count, suggesting that hydrostatic lung edema can be associated with a concomitant inflammatory process.

Conclusions

There are significant differences between the s-Cath and mini-BAL sampling techniques, indicating that these procedures cannot be used interchangeably for studying the lung inflammatory response in patients with acute hypoxaemic lung injury.
Prognostic Significance of New Immunohistochemistry Scoring of p53 Protein Expression in Cutaneous Squamous Cell Carcinoma of Mice
Authors: Bukhari Mulazim Hussain , Niazi Shahida , Anwar Muhammad , Chaudhry Naseer Ahmed , Naeem Samina
Published: August 2009

This study was conducted to investigate the prognostic value and therapeutic response of treatment modalities on p53 protein expression and AgNOR index in squamous cell carcinoma (SCC). Furthermore, based on data, we proposed a new p53 immunohistochemistry (IHC) scoring system. Sixty albino mice were given 7,12‐dimethylbenz[a]anthracine (DMBA) and 12‐O‐tetradecanoly Phorbol‐13‐acetate (TPA) to produce skin tumors. The retinoids were given after the development of tumors. p53 immunohistochemical and AgNOR staining was performed on the sections taken before and after the retinoid administration. p53 protein was expressed in 31 of the lesions (60.8%). AgNOR index was high in all 51 (100%) of the pretreated lesions. There was a marked decrease in the expression of p53 protein in 16/51 (31.4%) and AgNOR index in 36/51 (70.6%) in post‐treated mice. There was no decrease in the expression of both markers in mice harboring malignant neoplasms. p53 IHC scores were 0, I, and II in epidermal hyperplasia, papilloma, and dysplasia, respectively, while they were II, III, IV, and V in SCC in situ, well‐differentiated, moderately differentiated, and poorly differentiated SCCs, respectively. Alteration of p53 and AgNOR index occured during the development of SCC. The p53 IHC scores are directly related to the grades of malignancy. Both markers might be used as a supportive tool with routinely performed Hematoxylin and Eosin staining and may help in the diagnosis of SCC. The newly proposed p53 IHC scoring system will help histopathologists in making their differential diagnosis among benign, premalignant, and malignant lesions. It will also help the oncologists to assess the prognosis and effectiveness of their chemotherapy.
Intra‐operative Echographic Localization for Radioactive Ophthalmic Plaques in Choroidal Melanoma
Authors: Al Mahmoud Tahra , Mansour Magdi , Deschênes Jean , Edelstein Chaim , Burnier Miguel , Marcil Michel , Shenouda George , Corriveau Christine , Evans Michael
Published: August 2009

The objectives were to evaluate the beneficial effect of intra‐operative echographic plaque site localization and to assess the rate of complications of postplaque insertion. This paper is a descriptive study of 48 patients with choroidal melanoma who underwent iodine‐125 (I125) or ruthenium‐106 (Ru106) plaque radiotherapy with intra‐operative echographic confirmation of plaque placement with the aid of a nonradioactive plaque (dummy) at McGill University Health Centre from 1997 to 2003. Patients' mean age was 63.7 years; 52% (25/48) male, 48% (23/48) female. Twenty‐seven percent (13/48) of the tumors were confined to the right eye and 73% (35/48) to the left eye. Forty‐eight percent (23/48) of the tumors were located posterior to the equator, 14.6% (7/48) were anterior to the equator, 18.7% (9/48) in posterior pole, and 18.7% (9/48) at equator. Sixty‐nine percent (33/48) received I125 and 31% (15/48) had Ru106 treatment. Ninety percent of the dummy plaques were initially positioned suboptimally and required repositioning under echographic guidance. At mean follow‐up of 18.8 months, there was no tumor‐related death or metastasis, but one patient required enucleation. The dummy plaque technique under echographic visualization resulted in reduction of radioactive exposure time during surgery of up to 50%. Intra‐operative echographic utilization has the ability to localize precisely the tumor–plaque relationship, thereby optimizing the radiation delivered to the choroidal melanoma, while minimizing the surgeon's exposure time.
Role of Prognostic Factors in the Management of Pediatric Solid Tumors
Authors: Yanagisawa Takaaki , Bartels Ute , Bouffet Eric
Published: August 2009

The importance of prognostic factors in predicting outcome in pediatric oncology is largely recognized, and most current protocols tailor treatment based on risk stratification. Further refinements of classical staging systems are ongoing, and the future of pediatric oncology is in the development of strategies based on individual tumor characteristics. This review details significant advances in our understanding of prognostic factors in the most common pediatric solid tumors and potential applications for clinical management.
Selective Surgical Management of Well‐Differentiated Thyroid Cancer
Authors: Shaha Ashok
Published: August 2009

There has been a rapid rise in the incidence of thyroid cancer in the United States, along with more incidentalomas of the thyroid. Treatment of thyroid cancer revolves around appropriate surgical intervention, minimizing complications, and the use of adjuvant therapy in select circumstances. Prognostic features and risk‐group analysis are crucial in determining the appropriate treatment. Thyroid cancers are divided into low‐, intermediate‐, and high‐risk groups. Surgical treatment should adhere to the risk‐group analysis. The prognostic features in thyroid cancer are age, gender, size and grade of the tumor, extrathyroidal extension, and completeness of resection. The patient presenting with extrathyroidal extension needs extra attention in the operating room to remove all gross tumor during the initial surgical procedure to avoid future recurrences. Nodal metastasis generally has minimal implications; however, in older patients and those with poorly differentiated histology, it has major implications. Grading of the tumor is important, especially for understanding the poorly differentiated varieties of thyroid cancer, such as tall cell and insular. These patients do not respond well to RAI and are best followed with a PET scan. Overall survival in patients with well‐differentiated thyroid cancer exceeds 95%.
Mesothelioma and Environmental Exposure
Authors: Varga Csaba , Szendi Katalin
Published: August 2009

A novel animal model was developed to study the direct exposure of mesothelial cells to crocidolite and chrysotile asbestos fibers. Chemically pure and pretreated Union Internationale Centre le Cancer (UICC) samples were implanted into a peritoneal envelope (Kertai's fold) of Wistar rats. Following the 12‐month exposure, lack of mesothelioma induction was detected in all groups. Results suggest that the mechanism of mesothelioma formation is not a consequence of peritoneal physical exposure to the fibers.
HER‐2/neu Ile655Val Polymorphism and the Risk of Breast Cancer
Authors: Siddig Awatif , Mohamed Abdelrahim Osman , Kamal Hammed , Awad Salma , Hassan Ahmed H. , Zilahi Erika , Al‐Haj Mohammed , Bernsen Roos , Adem Abdu
Published: August 2009

Genetic alterations of the proto‐oncogene human epidermal growth factor receptor (HER‐2/neu) have been shown to induce malignant transformation and metastasis. Genotyping studies have addressed the association of codon 655 isoleucine to valine polymorphism located in the transmembrane coding region and the risk of breast cancer, but the results are inconsistent. In this study, we investigated the association of HER‐2/neu Ile655Val polymorphism and the risk of breast cancer in a Sudanese population. In addition, the joint effects of HER‐2/neu variants and our previously reported ESR1C325G polymorphism were tested for their association with breast cancer risk. Candidate single nucleotide polymorphism (SNP) in HER‐2/neu Ile655Val [db SNP rs1136200] was genotyped in breast cancer patients and in healthy controls that were randomly selected from the same age group as the patients. Genotyping was performed using a high‐throughput allelic discrimination method using real‐time PCR, and data on clinical features and demographic details were collected. Associations between genotype and breast cancer were assessed by means of logistic regression. The prevalence of Val/Val genotype was similar in patients of breast cancer and control subjects. In comparison with the Ile/Ile genotype, the Ile/Val had a borderline significantly (P= 0.06) higher risk of breast cancer (OR = 2.95, 95% CI: 0.97–8.96). Regarding the genotypic and allelic frequencies stratified by age and menopausal status, there were no significant associations. A significantly higher risk of breast cancer was observed among homozygous carriers of ESR1325 CC genotype and heterozygous carriers of HER‐2/neu655 Ile/Val genotype (P= 0.05; adjusted OR = 4.9, 95% CI: 1.0–24). The association of HER‐2/neu Ile655Val polymorphism and the risk of breast cancer was borderline significant with the heterozygous carrier being at higher risk. However, the frequency of different polymorphic variants varies with ethnicity. The results of this study suggest that a significant gene–gene interaction between ESR1325C (previously reported) and HER‐2/neu Ile655Val variants may jointly contribute to a higher risk of breast cancer.
The Potential of PARP Inhibitors in Genetic Breast and Ovarian Cancers
Authors: Drew Yvette , Calvert Hilary
Published: August 2009

The abundant nuclear enzyme poly(ADP‐ribose) polymerase‐1 (PARP‐1), represents an important novel target in cancer therapy. PARP‐1 is essential to the repair of DNA single‐strand breaks via the base excision repair pathway. Inhibitors of PARP‐1 have been shown to enhance the cytotoxic effects of ionizing radiation and DNA damaging chemotherapy agents, such as the methylating agents and topoisomerase I inhibitors. There are currently at least five PARP inhibitors in clinical trial development. Recent in vitro and in vivo evidence suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers, but as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer associated (BRCA) 1 and 2 genes. This theory of selectively exploiting cells defective in one DNA repair pathway by inhibiting another is a major breakthrough in the treatment of cancer. BRCA1/2 mutations are responsible for the majority of genetic breast/ovarian cancers, known as the hereditary breast ovarian cancer syndrome. This review summarizes the preclinical and clinical evidence for the potential of PARP inhibitors in genetic breast and ovarian cancers.
Laparoscopy in Gastrointestinal Malignancies
Authors: Torab Fawaz Chikh , Bokobza Bernard , Branicki Frank
Published: August 2009

This paper presents an update of the role of minimally invasive surgery (MIS) in gastrointestinal malignancy. A review of indications, surgical technique, and radicality of laparoscopy in the field of gastrointestinal cancer surgery is discussed. The feasibility and safety of laparoscopic procedures are compared with established and implemented standards in the diagnosis and treatment of oncological disorders. It is important to appreciate that only the “access” is different with all its attendant advantages. The use of laparoscopy in tumor staging and palliative and curative resection is evaluated on review of the literature, and special indications for a laparoscopic approach in gastrointestinal malignancy in different organs are discussed. In conclusion, MIS is safe and feasible, with many short‐term advantages; long‐term results should be further assessed in randomized controlled studies. Until the outcomes of such studies are available MIS for malignant disease should be performed by experienced surgeons in specialized centers.
Magnetic Resonance Imaging of Endometrial and Cervical Cancer
Authors: Sahdev Anju , Reznek Rodney H.
Published: August 2009

In this article we review the current and developing roles of magnetic resonance imaging (MRI) in endometrial and cervical cancer. In endometrial cancer, the purpose of MRI is to stage the primary tumor and in particular to identify myometrial and cervical invasion and extra‐uterine disease, thereby informing preoperative surgical planning. MRI is also used to safely select young patients suitable for fertility‐preserving medical management. In cervical cancer, MRI has an established role in local staging and in assessing proximal extension of tumors in young women for feasibility of fertility‐preserving surgery. It is used to plan radiotherapy for primary tumors in cervical cancer and particularly for conformal radiotherapy to deliver optimal doses to the tumor sites, while limiting unwanted exposure of bowel and other pelvic organs. In both cancers, MRI is used for diagnosing nodal disease, surveillance, detection of recurrence, and evaluation of complications secondary to treatment.
Radical Prostatectomy
Authors: Hammad Fayez T.
Published: August 2009

The first radical prostatectomy was performed in 1904. Since then, it has become one of the main treatment options for patients with prostate cancer, especially those with organ‐confined disease. As it is the case in all types of malignancies, the treatment choice for the patient with prostate cancer depends on several considerations, the most important of which is the ability of the treatment modality to control disease. This review provides a brief comparison between radical prostatectomy and other main treatment options of prostate cancer, such as “watchful waiting” and radiation therapy, in terms of cancer control. In addition, an overview is provided of the oncological outcomes following various techniques and approaches of radical prostatectomy including open retropubic, perineal, laparoscopic, and robot‐assisted surgery.
Interventional Pain Treatments for Cancer Pain
Authors: Christo Paul J. , Mazloomdoost Danesh
Published: August 2009

Cancer pain is prevalent and often multifactorial. For a segment of the cancer pain population, pain control remains inadequate despite full compliance with the WHO analgesic guidelines including use of co‐analgesics. The failure to obtain acceptable pain or symptom relief prompted the inclusion of a fourth step to the WHO analgesic ladder, which includes advanced interventional approaches. Interventional pain‐relieving therapies can be indispensable allies in the quest for pain reduction among cancer patients suffering from refractory pain. There are a variety of techniques used by interventional pain physicians, which may be grossly divided into modalities affecting the spinal canal (e.g., intrathecal or epidural space), called neuraxial techniques and those that target individual nerves or nerve bundles, termed neurolytic techniques. An array of intrathecal medications are infused into the cerebrospinal fluid in an attempt to relieve refractory cancer pain, reduce disabling adverse effects of systemic analgesics, and promote a higher quality of life. These intrathecal medications include opioids, local anesthetics, clonidine, and ziconotide. Intrathecal and epidural infusions can serve as useful methods of delivering analgesics quickly and safely. Spinal delivery of drugs for the treatment of chronic pain by means of an implantable drug delivery system (IDDS) began in the 1980s. Both intrathecal and epidural neurolysis can be effective in managing intractable cancer‐related pain. There are several sites for neurolytic blockade of the sympathetic nervous system for the treatment of cancer pain. The more common sites include the celiac plexus, superior hypogastric plexus, and ganglion impar. Today, interventional pain‐relieving approaches should be considered a critical component of a multifaceted therapeutic program of cancer pain relief.
Febrile Neutropenia
Authors: Ellis Michael
Published: August 2009

This review summarizes the current status and diagnostic‐therapeutic challenges in febrile neutropenia. Patients with neutropenia‐associated infections have a poor prognosis. A large meta‐analysis of trials assessing prophylactic antibiotics has shown significant survival benefits; clinical significance of resistance is unclear. Administering broad‐spectrum antibiotics to established febrile neutropenic patients has become selective, vancomycin is withheld unless absolutely necessary, and low‐risk patients are identified with biological markers. Such patients are now managed with oral antibiotics at home or even without antibiotics. Protracted prolonged neutropenia is the setting par excellence for invasive fungal infections. Conventional amphotericin B administered to such risk patients reduces the incidence of fungal infections. New antifungal drugs have heightened efficacy and lowered toxicity. Novel antifungal diagnostic tests include imaging, particularly the CT “halo” sign (aspergillosis), and serology (glucan, galactomannan), and provide earlier diagnosis and treatment and better outcomes. Negative tests may indicate withholding antifungal therapy. High intermittent dosing of liposomal amphotericin B seems as safe and as effective as standard dosing regimens, but at half the drug acquisition cost. The use of nonantibiotic agents has offered alternative management strategies. Recombinant interleukin‐11 reduces bacteremia, through a cytoprotective mechanism on the gut. rhIL‐11 releases C‐reactive protein and causes shedding of soluble TNF receptor‐1, modulating the immunological milieu and the systemic inflammatory response. Other candidate molecules include RANTES and long‐pentraxin 3. Recombinant growth factors reduce febrile episodes, permitting completion of chemotherapy, increase overall survival, and minimize infection mortality.
Attenuated Bacteria as Effectors in Cancer Immunotherapy
Authors: Al‐Ramadi Basel K. , Fernandez‐Cabezudo Maria J. , El‐Hasasna Hussain , Al‐Salam Suhail , Attoub Samir , Xu Damo , Chouaib Salem
Published: August 2009

Despite the great strides made in understanding the basic biology of cancer and the multiple approaches to cancer therapy that have been utilized, cancer remains a major cause of death worldwide. The two properties that define the most successful tumors are low antigenicity, enabling cancer cells to escape immune system recognition, and high tumorigenicity, allowing the cells to proliferate aggressively and metastasize to other tissues. The development of novel anticancer therapies is aimed at enhancing the antigenicity of tumors and/or increasing the functional efficiency of various effector immune system cells. The use of obligate/facultative anaerobic bacteria, which preferentially replicate within tumor tissue, as an oncolytic agent is one of the innovative approaches to cancer therapy. Over the past several years, we have studied the properties of attenuated strains of Salmonella typhimurium, a facultative anaerobe, genetically engineered to express murine cytokines. Previously, we demonstrated that cytokine‐expressing strains have the capacity to modulate immunity to infection. Given the preferential tumor‐homing properties of attenuated Salmonella bacteria, the potential capacity of a cytokine‐encoding Salmonella strain to retard the growth of experimental melanomas was investigated. Mice pre‐implanted with melanoma cells were treated with an attenuated strain of S. typhimurium or with one of its derivatives expressing IL‐2. Our data demonstrate that IL‐2‐encoding Salmonella organisms were superior in suppressing tumor growth as compared to the parental noncytokine‐expressing strain. This supports the notion of using cytokine‐expressing attenuated Salmonella organisms in cancer therapy.
Investigation of Heat Stress Response in the Camel Fibroblast Cell Line Dubca
Authors: Thayyullathil Faisal , Chathoth Shahanas , Hago Abdulkader , Wernery Ulli , Patel Mahendra , Galadari Sehamuddin
Published: August 2009

We have used a camel cell line model (Dubca) to investigate the effect of heat stress on cell survival. The mechanism(s) of such survival response are very important not only for normal physiological function, but also, in pathological conditions, such as cancer. Those cells that have escaped the normal response to heat are an important model in helping us better understand the intricate signaling change(s) that might have occurred in changing a cell's phenotype from normal to cancerous. Our findings in this study indicate that unlike comparative fibroblast cells (L929), Dubca cells are quite resistant and survive the 42°C heat stress in a time‐dependent manner; indeed, the cells even show growth on par with those cells that are kept at the control temperature of 37°C. Expression levels of Akt, an important prosurvival kinase, are uniform, and irrespective of the experimental or control temperature, show basal control levels. In other words, there is no loss of Akt protein level following heat stress at 42°C. Similarly, no significant change in HSP70 expression level is observed. In contrast, the stress transcription factor c‐Jun, and the stress activated kinase (Jnk) were induced during this heat‐shock condition. This is in line with the fact that suppression of stress kinase Jnk renders cells thermoresistant. On the other hand, acquired tolerance to severe heat shock is associated with downregulation of Jnk.
Potential Inhibition of PDK1/Akt Signaling by Phenothiazines Suppresses Cancer Cell Proliferation and Survival
Authors: Choi Jang Hyun , Yang Yong Ryoul , Lee Seul Ki , Kim Sun‐Hee , Kim Yun‐Hee , Cha Joo‐Young , Oh Se‐Woong , Ha Jong‐Ryul , Ryu Sung Ho , Suh Pann‐Ghill
Published: August 2009

3′‐Phosphoinositide‐dependent kinase‐1 (PDK1) has been identified for its ability to phosphorylate and activate Akt. Accumulated studies have shown that the activation of the PDK1/Akt pathway plays a pivotal role in cell survival, proliferation, and tumorigenesis. Therefore, the PDK1/Akt pathway is believed to be a critical target for cancer intervention. In this paper, we report the discovery of a new function of phenothiazines, widely known as antipsychotics, inhibiting PDK1/Akt pathway. Upon epidermal growth factor (EGF) stimulation, phenothiazines specifically suppressed the kinase activity of PDK1 and the phosphorylation level of Akt. The inhibition of PDK1/Akt kinase resulted in suppression of EGF‐induced cell growth and induction of apoptosis in human ovary cancer cells. In particular, phenothiazines were highly selective for downstream targets of PDK1/Akt and did not inhibit the activation of phosphatidylinositol 3‐kinase (PI3K), EGFR, or extracellular signal‐regulated kinase 1/2 (ERK1/2). In particular, phenothiazines effectively suppressed tumor growth in nude mice of human cancer cells. Taken together, these findings provide strong evidence for novel function of phenothiazines, pharmacologically targeting PDK1/Akt for anticancer drug discovery.
Cerebellar Volume and Cerebellar Metabolic Characteristics in Adults with Dyslexia
Authors: Laycock Suzanna K. , Wilkinson Iain D. , Wallis Lauren I. , Darwent Gail , Wonders Sarah H. , Fawcett Angela J. , Griffiths Paul D. , Nicolson Roderick I.
Published: August 2009

Developmental dyslexia is associated with problems in a range of linguistic and non‐linguistic skills. Some of those problems have been attributed to dysfunction of the cerebellum and its associated neural systems. Two studies of cerebellar structure were undertaken by our group. In Study 1, white and grey matter volumes in the cerebellum were investigated in 10 dyslexic and 11 control adult male, right‐handed participants using whole‐brain volumetric MRI (3D‐T1‐weighted data sets with a spatial resolution of 0.8 × 0.8 × 0.8 mm3). The key finding was that the dyslexic group had a larger volume of white matter in both cerebellar hemispheres, differences that remained significant even when adjusting for total cerebellar volume. In Study 2, with the same participants, long‐echo‐time proton spectroscopy was used to investigate the ratios of the metabolites choline (Cho), N‐acetylaspartate (NAA), and creatine (Cr) in the cerebellar hemispheres and vermis. Two significant differences were found: The dyslexic group had a lower ratio of NAA/Cho in the right cerebellar hemisphere together with a higher ratio of Cho/Cr in the left cerebellar hemisphere. Although it is difficult to interpret the volumetric and spectroscopic results unambiguously, taken together they suggest two possible interpretations: excessive connectivity or abnormal myelination.
Logographic Kanji versus Phonographic Kana in Literacy Acquisition
Authors: Koyama Maki S. , Hansen Peter C. , Stein John F.
Published: August 2009

It is well‐established that phonological skills are important for literacy acquisition in all scripts. However, the role of visual skills is less well understood. For logographic scripts in which a symbol represents a whole word or a meaningful unit, the importance of visual memory in literacy acquisition might be expected to be high because of the visual complexity of logographic characters, but in fact its role remains poorly understood. The Japanese writing system uses both phonographic “Kana” and logographic “Kanji” scripts concurrently and thus allows for the assessment of the contribution of phonological and visual processing to literacy acquisition in these two different scripts in the same language. We tested 74 Japanese children (39 second graders and 35 fourth graders) on a range of literacy, sensory, and cognitive tasks. We found that Kana literacy performance was significantly predicted by low‐level sensory processing (both auditory frequency modulation sensitivity and visual motion sensitivity) as well as phonological awareness, but not by visual memory. This result is largely consistent with previous studies in other phonographic scripts such as English. In contrast, Kanji literacy performance was strongly predicted by visual memory (particularly visual long‐term memory), but not by either low‐level sensory processing or phonological awareness. Our results show differences in the skills that predict literacy performance in phonographic Kana and logographic Kanji, as well as providing experimental evidence that visual memory is important when learning Kanji. Therefore, children's literacy problems and remediation programs should be considered in the context of the script in which children are learning to read and write.
Neurocognitive Basis of Implicit Learning of Sequential Structure and Its Relation to Language Processing
Authors: Conway Christopher M. , Pisoni David B.
Published: August 2009

The ability to learn and exploit environmental regularities is important for many aspects of skill learning, of which language may be a prime example. Much of such learning proceeds in an implicit fashion, that is, it occurs unintentionally and automatically and results in knowledge that is difficult to verbalize explicitly. An important research goal is to ascertain the underlying neurocognitive mechanisms of implicit learning abilities and understand its contribution to perception, language, and cognition more generally. In this article, we review recent work that investigates the extent to which implicit learning of sequential structure is mediated by stimulus‐specific versus domain‐general learning mechanisms. Although much of previous implicit learning research has emphasized its domain‐general aspect, here we highlight behavioral work suggesting a modality‐specific locus. Even so, our data also reveal that individual variability in implicit sequence learning skill correlates with performance on a task requiring sensitivity to the sequential context of spoken language, suggesting that implicit sequence learning to some extent is domain‐general. Taking into consideration this behavioral work, in conjunction with recent imaging studies, we argue that implicit sequence learning and language processing are both complex, dynamic processes that partially share the same underlying neurocognitive mechanisms, specifically those that rely on the encoding and representation of phonological sequences.
Implicit Learning and Dyslexia
Authors: Folia Vasiliki , Uddén Julia , Forkstam Christian , Ingvar Martin , Hagoort Peter , Petersson Karl Magnus
Published: August 2009

Several studies have reported an association between dyslexia and implicit learning deficits. It has been suggested that the weakness in implicit learning observed in dyslexic individuals may be related to sequential processing and implicit sequence learning. In the present article, we review the current literature on implicit learning and dyslexia. We describe a novel, forced‐choice structural “mere exposure” artificial grammar learning paradigm and characterize this paradigm in normal readers in relation to the standard grammaticality classification paradigm. We argue that preference classification is a more optimal measure of the outcome of implicit acquisition since in the preference version participants are kept completely unaware of the underlying generative mechanism, while in the grammaticality version, the subjects have, at least in principle, been informed about the existence of an underlying complex set of rules at the point of classification (but not during acquisition). On the basis of the “mere exposure effect,” we tested the prediction that the development of preference will correlate with the grammaticality status of the classification items. In addition, we examined the effects of grammaticality (grammatical/nongrammatical) and associative chunk strength (ACS; high/low) on the classification tasks (preference/grammaticality). Using a balanced ACS design in which the factors of grammaticality (grammatical/nongrammatical) and ACS (high/low) were independently controlled in a 2 × 2 factorial design, we confirmed our predictions. We discuss the suitability of this task for further investigation of the implicit learning characteristics in dyslexia.
G Protein–Coupled Receptor Structures, Molecular Associations, and Modes of Regulation
Authors: Miller Laurence J.
Published: August 2009

G protein–coupled receptors are present on every excitable and regulatable cell in the body and represent important potential sites for drug action. This group of molecules already represents the most common target for currently approved drugs. With recent advances in our understanding of detailed molecular structure, mechanisms of activation, unique molecular associations, and cellular and biochemical mechanisms of regulation of these receptors, development and refinement of receptor‐active drugs should benefit substantially. In this report, key past accomplishments and possible future directions for this field of research are reviewed.
Molecular Mechanisms of TRPV4‐Mediated Neural Signaling
Authors: Liedtke Wolfgang
Published: August 2009

In signal transduction of metazoan cells, ion channels of the family of transient receptor potential (TRP) have been identified to respond to diverse external and internal stimuli, among them osmotic stimuli. This review highlights a specific member of the TRPV subfamily, the TRPV4 channel, initially named vanilloid‐receptor related osmotically activated channel (VR‐OAC) or OTRPC4. In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue osmo‐ and mechanosensory deficits of the TRPV mutant strain osm‐9 in Caenorhabditis elegans. This is an astounding finding given the <26% orthology between OSM‐9 and TRPV4 proteins. Here, recent findings pertaining to TRPV4's mechano‐ and osmosensory function in endothelia, in the alveolar unit of the lung, and in intestinal sensory innervation are reviewed, namely, transduction of mechanical shear stress in endothelia, maintenance of alveolar integrity on the endothelial side, and intestinal mechanosensation of noxious stimuli by dorsal root ganglion sensory neurons, which can be potently sensitized to mechanical stimuli by activation of the proteinase‐activated receptor 2 (PAR‐2), in a strictly TRPV4‐dependent manner.
The Vasoactive Intestinal Peptide Gene Is a Key Modulator of Pulmonary Vascular Remodeling and Inflammation
Authors: Said Sami I.
Published: August 2009

Pulmonary vascular remodeling and inflammation often coexist in clinical and experimentally induced pulmonary arterial hypertension (PAH). In some instances, the pulmonary hypertension may be the primary, or at least the initial, problem, while inflammatory or autoimmune responses appear to initiate or dominate the picture in other cases. Based on studies in a model of PAH resulting from targeted deletion of the neuropeptide vasoactive intestinal peptide (VIP) gene, we propose that, at least in this experimental model, but possibly also in other situations, both vascular remodeling and inflammation may be mediated by one and the same mechanism: uncontrolled activation of calcineurin–NFAT (nuclear factor of activated T cells) signaling. If this hypothesis is validated, VIP would emerge as an endogenous modulator of pulmonary vascular remodeling and inflammation, through its suppression of NFAT activation.
Discovery of Pituitary Adenylate Cyclase‐Activating Polypeptide‐Regulated Genes through Microarray Analyses in Cell Culture and In Vivo
Authors: Eiden Lee E. , Samal Babru , Gerdin Matthew J. , Mustafa Tomris , Vaudry David , Stroth Nikolas
Published: August 2009

Pituitary adenylate cyclase‐activating polypeptide (PACAP) is an evolutionarily well conserved neuropeptide with multiple functions in the nervous, endocrine, and immune systems. PACAP provides neuroprotection from ischemia and toxin exposure, is anti‐inflammatory in gastric inflammatory disease and sepsis, controls proliferative signaling pathways involved in neural cell transformation, and modulates glucohomeostasis. PACAP‐based, disease‐targeted therapeutics might thus be both effective and benign, enhancing homeostatic responses to behavioral, metabolic, oncogenic, and inflammatory stressors. PACAP signal transduction employs synergistic regulation of calcium and cyclic adenosine monophosphate (cAMP), and noncanonical activation of both calcium‐ and cAMP‐dependent processes. Pharmacological activation of PACAP signaling should consequently have highly specific effects even in vivo. Here, a combined cellular biochemical, pharmacologic, transcriptomic, and bioinformatic approach to understanding PACAP signal transduction by identifying PACAP target genes with oligonucleotide‐ and cDNA‐based microarray is described. Calcium‐ and cAMP‐dependent PACAP signaling pathways for regulation of genes encoding proteins required for neuritogenesis, changes in cell morphology, and cell survival have been traced in PC12 cells. Pharmacological experiments have linked gene expression to cell physiological responses in this system, in which gene silencing can also be employed to confirm the functional significance of induction of specific transcripts. Differential transcriptional responses to metabolic, ischemic, and other stressors in wild type compared to PACAP‐deficient mice establish in principle which PACAP‐responsive transcripts in culture are PACAP‐dependent in vivo. Bioinformatic approaches aid in creating a pipeline for identifying neuropeptide‐regulated genes, validating their cellular functions, and defining their expression in the context of neuropeptide signaling physiology, required for discovery of new targets for drug action.
Molecular Imaging to Biomarker Development in Neuroscience
Authors: Frost J. James
Published: August 2009

CNS drug candidates fail approval in over 90% of the cases due to poor targeting, lack of efficacy, and/or unacceptable side effects. In vivo imaging offers a pathway to derisk drug molecules at each stage of development, but more research and development is needed to fully realize this potential. The greatest activity is in the use of target biomarkers, but those for disease mechanism, efficacy, and toxicological effects are under study and urgently needed. Many of the biomarker tracers can later be developed as new diagnostic imaging agents and then used to guide individual molecular therapy. Realization of this goal will require ongoing collaborative research and development among universities, pharmaceutical companies, biotechnology, the contract research organization (CRO) industry, diagnostic companies, and producers and distributors of radiopharmaceuticals. During the past decade there has been a progressive merger of the interests of the pharmaceutical industry and academia in the area of molecular biomarker imaging in human brain disease. Historically, academia has been more focused on disease mechanisms, etiology, diagnosis, and treatment monitoring. The pharmaceutical industry has concentrated more on medication development, drug pharmacokinetics, and surrogate treatment end points. In the era of personalized medicine, these interests have evolved to a continuum where the knowledge of diagnosis and molecular mechanism of disease from imaging not only guides new medication development but also is beginning to direct individualized drug choice and dosage.
Hematological and Plasma Biochemistry of the Adult Wild African Grasscutter (Thryonomys swinderianus)
Authors: Opara Maxwell N. , Fagbemi Benjamin O.
Published: August 2009

Hematological and plasma biochemical values of wild grasscutters were evaluated to determine their potential to transmit zoonotic pathogens. Three 5‐mL blood samples were collected from each of 1000 grasscutters caught in the wild for hematology, biochemical, and parasitological tests. Hematological and biochemical values were compared with those from captive‐reared grasscutters. There are significantly (P < 0.05) higher lymphocyte, eosinophil, and basophil values for wild grasscutters compared to those that are captive reared. Parasitological examination revealed a 15% prevalence of blood protozoa in the wild grasscutters. Blood pathogens encountered were Trypanosoma sp. (66.7%) and Plasmodium sp. (33.3%), with 20.7% mixed infection. Sex does not significantly (P > 0.05) affect blood protozoa infection, while season does. We therefore concluded that wild grasscutters serve as efficient reservoir hosts for agents of African trypanosomiasis and malaria in the tropical humid rainforest region of Nigeria.
Prevalence of Leptospirosis in Dairy Cattle from Small Rural Production Units in Toluca Valley, State of Mexico
Authors: Leon L. L. , Garcia R. C. , Diaz C. O. , Valdez R. B. , Carmona G. C. A. , Velazquez B. L. G.
Published: August 2009

In order to know the seroprevalence ofLeptospiraspp. in stabled dairy cattle, a study was conducted from 2004 to 2006 in which 416 sera were tested using a microscopic agglutination test conducted on microplates. A collection of culture reference antigens, each representing a serogroup, was used for these tests. Results showed that 10.33% (43) of the animals had antibody titers ranging from 1:100 to 1:1600. The main serovars detected in these tests wereL. interrogansserovarhardjoand L.interrogansserovarcanicola. It is important to note that these serovars represent a high risk for transmission to other susceptible animal species, between individuals, and to human health. This serological survey provides useful information establishing the presence or absence of these serovars in this type of herd. The range of antigens used in this study included serovars representative of all common serogroups.
Comparing Therapeutic Efficacy between Ivermectin, Selamectin, and Moxidectin in Canaries during Natural Infection with Dermanyssus gallinae
Authors: Todisco Gianluca , Paoletti Barbara , Giammarino Angelo , Manera Maurizio , Sparagano Olivier A. E. , Iorio Raffaella , Giannella Benedetta , Robbe Domenico
Published: August 2009

The aim of this study was to compare the efficacy of three spot‐on drugs on canaries during Dermanyssus gallinae natural infections and during the breeding season. Three groups of canary couples (seven couples each) were included: group A was treated with ivermectin, B with selamectin, and C with moxidectin. All the drugs were administered topically infrascapularly. The parasitic charge was estimated before the treatment (t0) and after 8 (t1), 16 (t2), 24 (t3), and 32 (t4) days following the initial treatment. No significant differences were detected among the three tested drugs for the five repeats for each of the four mite stages (egg, larva, nymphs, and fed and unfed adults). With regard to the decrease in the mean numbers of red mites, ivermectin and selamectin exerted their efficacy at t2, contrary to moxidectin at t3.
Secreted Proteins of Avibacterium paragallinarum Are Lethal for Chicken Embryo
Authors: Pérez‐Márquez Víctor , Pérez‐Méndez Alma , Ibarra‐Caballero Jorge , Gómez‐Lugo Gabriela , Vázquez‐Cruz Candelario , Vaca Sergio , Negrete‐Abascal Erasmo
Published: August 2009

Avibacterium paragallinarum causes infectious coryza in chickens. This bacterium secretes proteins of 110 kDa (a putative RTX protein) and 120 kDa. Expression of these proteins increases by the addition of CaCl2, MgSO4, MnSO4, or ferric ammonium citrate and diminishes with CuSO4 or ZnCl2. Protein expression is optimal at 37°C and pH 7.5. Mortality (90–100%) of chicken embryos was observed when secreted proteins (SPs) from A. paragallinarum reference or field isolates (serogroup A or C) were inoculated via yolk sac and was not observed when SPs from A. avium, a chicken respiratory tract indigenous bacterium, were inoculated. A. paragallinarum SPs could contain toxins responsible for the embryo deaths. Indeed, presence of the putative RTX protein of 110 kDa was confirmed by Western blotting with antibodies against the Actinobacillus pleuropneumoniae RTX ApxI, a closely related RTX protein.
Toward a PCR‐Independent Molecular Diagnosis of Veterinary and Medically Relevant Pathogenic Organisms
Authors: Partington Matthew W. , Masic Dino , Nicholson Audrey , Perry John , Berrington Andrew , West Jonatan , Sparagano Olivier A. E.
Published: August 2009

Bloodstream infections caused by bacteria and fungi are a major problem worldwide. These bloodstream infections can affect both people and livestock, placing a significant burden upon developed and developing economies. In this paper we describe a multiplexed testing format, which can identify a range of bacteria and fungi within a single blood sample. Key to this technique is the specificity and sensitivity of the nucleotide probes that capture the sample. The sensitivity and specificity of the probes may allow detection of disease‐causing microorganisms without the need for polymerase chain reaction amplification if the dynamics of probe binding can be observed in real time.
Evaluation of BCG Vaccine and Mycobacterium bovis Culture Filtrate Proteins against Bovine Tuberculosis
Authors: Díaz‐Otero Fernando , Padilla Jesus , Jaramillo Laura , González Dante , Arriaga Camila
Published: August 2009

The objective of this study was to evaluate the degree of protection against TB of three immunogens in calves experimentally challenged with a pathogenic Mycobacterium bovis strain by identification of lesions during necropsy. Twenty‐four calves free of TB were distributed into four groups: group 1 was inoculated with M. bovis CFPE, group 2 with CFPE/IFN‐γ, group 3 with M. bovis BCG, and group 4 remained as control. After 6 months all animals were challenged with an M. bovis field strain, and 6 months later the animals were euthanized and the presence of lesions was evaluated. Several degrees of protection were observed in the vaccinated groups, particularly in the group vaccinated with BCG, as shown by the absence or decrease in severity of lesions. Vaccination could be useful in high‐prevalence zones where it is economically unfeasible to slaughter animals.
Use of Phlebotomine Sand Flies as Indicator of Leishmania Prevalence in an Endemic Area
Authors: Torina Alessandra , Sole Mery , Reale Stefano , Vitale Fabrizio , Caracappa Santo
Published: August 2009

An entomological survey was conducted on phlebotomine sand flies to discover the presence of Leishmania parasites in six Sicilian provinces. During the season from June to October 2005, 20,346 sand fly specimens were collected by using a “black light” trap in eight cattle and sheep farms. The most prevalent species was Phlebotomus perfiliewi (51.60%) followed by P. perniciosus (24.37%), and Sergentomyia minuta (24.03%). Among the 11,441 females collected, 284 (2.70%) were gravid and 708 (6.74%) were blood‐fed females. A total of 194 gravid females, 274 blood‐fed females, and 254 females with no evidence of blood meal were analyzed for L. infantum by PCR analysis, showing 9.79% gravid females, 5.84% blood‐fed females, and 5.51% females with no evidence of blood meal positive for Leishmania DNA. These results support the use of gravid female sand flies for the evaluation of prevalence of Leishmania.