The humoral immune system in higher vertebrates is unique in its ability to generate highly diverse antibody responses against most pathogens as well as against certain malignancies. Several ...technologies have been developed to exploit this vast source of potentially therapeutic antibodies, including hybridoma technology, phage display and yeast display. Here, we present a novel, high-throughput technology (the Symplex Technology) for rapid direct cloning and identification of human antigen-specific high-affinity antibodies from single antibody-producing cells of immune individuals. The utility of the technology was demonstrated by isolation of diverse sets of unique high-affinity antibodies against tetanus toxoid and influenza virus from immunized volunteers. Hence, the Symplex Technology is a new method for the rapid isolation of high-affinity antibodies directly from humans.
Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers ...with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.
Abstract We present the preliminary results of a study involving a group of consecutive patients who underwent lower border onlay grafting, limited to the symphyseal area, in preparation for implant ...insertion. This technique allows for maximum-sized implants, followed by prosthetic rehabilitation. The main advantage of this method is the minimal risk of damage to the mental nerve. Sixteen patients were followed for a period of 6 months to 4 years and all were free of neurosensory disturbances. Eight had a removable overdenture placed and were satisfied with the result. This surgical approach allows the patient to wear their dentures during the healing period. A further advantage of lower border grafting over intraoral upper border grafting is that mucosal dehiscences are not seen.
The cardiac manifestations of a neuroendocrine tumour are referred to as carcinoid heart disease (CaHD) and are associated with a poor prognosis. Surgical intervention is the only proven therapeutic ...option and may prolong survival and quality of life. No consensus has been reached internationally with regard to screening for CaHD and the optimal timing for surgery. Although limited evidence is available on this matter, a trend towards early surgery and subsequent reduced mortality has been observed. In this review we provide an overview of the current understanding and propose a protocol to guide cardiologists in the screening for CaHD and the timing of referral to a specialised surgical centre.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the ...field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Abstract Monocyte derived dendritic cells (moDC) electroporated with tumor associated antigen derived mRNA can elicit specific T cells against tumor cells in vivo . IL21 has been shown to enhance ...activation and cytotoxicity in CD8+ T cells. We therefore investigated in vitro effects on human CD8+ T-cells after stimulation with IL21 mRNA electroporated moDC. Codon modification of the IL21 gene significantly enhanced IL21 production upon electroporation of moDC. Tumor associated antigen specific CTL induction efficiency was significantly enhanced when codon modified IL21 mRNA was co-electroporated with tumor associated antigen mRNA. Tumor associated antigen specific T cells induced by codon modified IL21-DC demonstrated increased cytotoxic capacity and killing compared to control cultures. In conclusion, ectopic expression of codon modified IL21 by moDC enhances the priming efficiency of the DC as well as the cytotoxic potential of the induced CTL.
To revise the static and dynamic normative values for the two-point discrimination test and to examine its applicability and validity in patients with a polyneuropathy.
Two-point discrimination ...threshold values were assessed in 427 healthy controls and 99 patients mildly affected by a polyneuropathy. The controls were divided into seven age groups ranging from 20-29, 30-39,..., up to 80 years and older; each group consisted of at least 30 men and 30 women. Two-point discrimination examination took place under standardised conditions on the index finger. Correlation studies were performed between the scores obtained and the values derived from the Weinstein Enhanced Sensory Test (WEST) and the arm grade of the Overall Disability SumScore (ODSS) in the patients' group (validity studies). Finally, the sensitivity to detect patients mildly affected by a polyneuropathy was evaluated for static and dynamic assessments.
There was a significant age-dependent increase in the two-point discrimination values. No significant gender difference was found. The dynamic threshold values were lower than the static scores. The two-point discrimination values obtained correlated significantly with the arm grade of the ODSS (static values: r = 0.33, p = 0.04; dynamic values: r = 0.37, p = 0.02) and the scores of the WEST in patients (static values: r = 0.58, p = 0.0001; dynamic values: r = 0.55, p = 0.0002). The sensitivity for the static and dynamic threshold values was 28% and 33%, respectively.
This study provides age-related normative two-point discrimination threshold values using a two-point discriminator (an aesthesiometer). This easily applicable instrument could be used as part of a more extensive neurological sensory evaluation.
Aliment Pharmacol Ther 31, 432–439
Summary
Background Guaiac‐based faecal occult blood tests (g‐FOBTs) are most commonly used in colorectal cancer (CRC) screening programmes. Faecal immunochemical ...tests (FITs) are thought to be superior.
Aim To compare performance of a g‐FOBT and a quantitative FIT for detection of CRCs and advanced adenomas in a colonoscopy‐controlled population.
Methods We assessed sensitivity and specificity of both FIT (OC‐sensor) and g‐FOBT (Hemoccult‐II) prior to patients’ scheduled colonoscopies.
Results Of the 62 invasive cancers detected in 1821 individuals, g‐FOBT was positive in 46 and FIT in 54 (74.2% vs. 87.1%, P = 0.02). Among 194 patients with advanced adenomas, g‐FOBT was positive in 35 and FIT in 69 (18.0% vs. 35.6%, P < 0.001). Sensitivity for screen relevant tumours (197 advanced adenomas and 28 stage I or II cancers) was 23.0% for g‐FOBT and 40.5% for FIT (P < 0.001). Specificity of g‐FOBT compared to FIT for the detection of cancer was 95.7% vs. 91.0%, P < 0.001) and for advanced adenomas (97.4% vs. 94.2%, P < 0.001).
Conclusions Faecal immunochemical test is more sensitive for CRC and advanced adenomas. Sensitivity of FIT for screen relevant tumours, early‐stage cancers and advanced adenomas, is significantly higher. Specificity of g‐FOBT is higher compared with FIT.
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric ...manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study.
After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out.
Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test–retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures.
Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.
PDF
