Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary

<p>Abstract</p> <p>Background</p> <p>We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue.</p> <p>Methods</p> <p>The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples.</p> <p>Results</p> <p>By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors.</p> <p>Conclusion</p> <p>The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that human monoclonal antibodies 27.F7 and 27.B1 should be further evaluated as potential diagnostic tools.</p

Surface electromyography pattern of human swallowing

<p>Abstract</p> <p>Background</p> <p>The physiology of swallowing is characterized by a complex and coordinated activation of many stomatognathic, pharyngeal, and laryngeal muscles. Kinetics and electromyographic studies have widely investigated the pharyngeal and laryngeal pattern of deglutition in order to point out the differences between normal and dysphagic people. In the dental field, muscular activation during swallowing is believed to be the cause of malocclusion.</p> <p>Despite the clinical importance given to spontaneous swallowing, few physiologic works have studied stomatognathic muscular activation and mandibular movement during spontaneous saliva swallowing.</p> <p>The aim of our study was to investigate the activity patterns of the mandibular elevator muscles (masseter and anterior temporalis muscles), the submental muscles, and the neck muscles (sternocleidomastoid muscles) in healthy people during spontaneous swallowing of saliva and to relate the muscular activities to mandibular movement.</p> <p>Methods</p> <p>The spontaneous swallowing of saliva of 111 healthy individuals was analyzed using surface electromyography (SEMG) and a computerized kinesiography of mandibular movement.</p> <p>Results</p> <p>Fifty-seven of 111 patients swallowed without occlusal contact (SNOC) and 54 individuals had occlusal contact (SOC). The sternocleidomastoid muscles showed a slight, but constant activation during swallowing. The SEMG of the submental and sternocleidomastoid muscles showed no differences between the two groups. The SEMG of the anterior temporalis and masseter muscles showed significant differences (p < 0.0001). The duration of swallowing was significantly higher in the SNOC subjects. Gender and age were not related to electromyographic activation. Healthy SOC and SNOC behaved in different ways.</p> <p>Conclusion</p> <p>The data suggest that there is not a single "normal" or "typical" pattern for spontaneous saliva swallowing. The polygraph seemed a valuable, simple, non-invasive and reliable tool to study the physiology of swallowing.</p

Parental use of the Internet to seek health information and primary care utilisation for their child: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Using the Internet to seek health information is becoming more common. Its consequences on health care utilisation are hardly known in the general population, in particular among children whose parents seek health information on the Internet. Our objective was to investigate the relationship between parental use of the Internet to seek health information and primary care utilisation for their child.</p> <p>Methods</p> <p>This cross-sectional survey has been carried out in a population of parents of pre-school children in France. The main outcome measure was the self-reported number of primary care consultations for the child, according to parental use of the Internet to seek health information, adjusted for the characteristics of the parents and their child respectively, and parental use of other health information sources.</p> <p>Results</p> <p>A total of 1 068 out of 2 197 questionnaires were returned (response rate of 49%). No association was found between parental use of the Internet to seek health information and the number of consultations within the last 12 months for their child. Variables related to the number of primary care consultations were characteristics of the child (age, medical conditions, homeopathic treatment), parental characteristics (occupation, income, stress level) and consultation of other health information sources (advice from pharmacist, relatives).</p> <p>Conclusion</p> <p>We did not find any relationship between parental use of the Internet to seek health information and primary care utilisation for children. The Internet seems to be used as a supplement to health services rather than as a replacement.</p

Health information seeking on the Internet: a double divide? Results from a representative survey in the Paris metropolitan area, France, 2005–2006

<p>Abstract</p> <p>Background</p> <p>The Internet is a major source of information for professionals and the general public, especially in the field of health. However, despite ever-increasing connection rates, a digital divide persists in the industrialised countries. The objective of this study was to assess the determinants involved in: 1) having or not having Internet access; and 2) using or not using the Internet to obtain health information.</p> <p>Methods</p> <p>A cross-sectional survey of a representative random sample was conducted in the Paris metropolitan area, France, in the fall of 2005 (n = 3023).</p> <p>Results</p> <p>Close to 70% of the adult population had Internet access, and 49% of Internet users had previously searched for medical information. Economic and social disparities observed in online health information seeking are reinforced by the economic and social disparities in Internet access, hence a double divide. While individuals who reported having a recent health problem were less likely to have Internet access (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53–0.98), it is they who, when they have Internet access, are the most likely to search for health information (OR = 1.44, 95% CI = 1.11–1.87).</p> <p>Conclusion</p> <p>In the French context of universal health insurance, access to the Internet varies according to social and socioeconomic status and health status, and its use for health information seeking varies also with health beliefs, but not to health insurance coverage or health-care utilisation. Certain economic and social inequalities seem to impact cumulatively on Internet access and on the use of the Internet for health information seeking. It is not obvious that the Internet is a special information tool for primary prevention in people who are the furthest removed from health concerns. However, the Internet appears to be a useful complement for secondary prevention, especially for better understanding health problems or enhancing therapeutic compliance.</p

Bovine Lactoferrin Counteracts Toll-Like Receptor Mediated Activation Signals in Antigen Presenting Cells

Lactoferrin (LF), a key element in mammalian immune system, plays pivotal roles in host defence against infection and excessive inflammation. Its protective effects range from direct antimicrobial activities against a large panel of microbes, including bacteria, viruses, fungi and parasites, to antinflammatory and anticancer activities. In this study, we show that monocyte-derived dendritic cells (MD-DCs) generated in the presence of bovine LF (bLF) fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion. Moreover, these cells are weak activators of T cell proliferation and retain antigen uptake activity. Consistent with an impaired maturation, bLF-MD-DC primed T lymphocytes exhibit a functional unresponsiveness characterized by reduced expression of CD154 and impaired expression of IFN-γ and IL-2. The observed imunosuppressive effects correlate with an increased expression of molecules with negative regulatory functions (i.e. immunoglobulin-like transcript 3 and programmed death ligand 1), indoleamine 2,3-dioxygenase, and suppressor of cytokine signaling-3. Interestingly, bLF-MD-DCs produce IL-6 and exhibit constitutive signal transducer and activator of transcription 3 activation. Conversely, bLF exposure of already differentiated MD-DCs completely fails to induce IL-6, and partially inhibits Toll-like receptor (TLR) agonist-induced activation. Cell-specific differences in bLF internalization likely account for the distinct response elicited by bLF in monocytes versus immature DCs, providing a mechanistic base for its multiple effects. These results indicate that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergo activation and to promote Th1 responses. Overall, these bLF-mediated effects may represent a strategy to block excessive DC activation upon TLR-induced inflammation, adding further evidence for a critical role of bLF in directing host immune function

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.</p> <p>Methods</p> <p>We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.</p> <p>Results</p> <p>Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.</p> <p>Conclusion</p> <p>The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.</p

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease