Production and characterization of monoclonal antibodies specific for the murine T cell receptor ζ chain

The T cell receptor (TCR) comprises an antigen-specific β heterodimer non-covalently associated with the CD3 γδε and TCR ζ subunits. Both the CD3 and TCR ζ subunits are proposed to be responsible for the intracellular signal-transduction events. We report here the production of eight monoclonal antibodies (mAbs) that bind in an ELISA assay to a 113 amino acid synthetic peptide corresponding to the cytoplasmic domain of TCR ζ. Western blot analysis of anti-CD8 precipitates of lysates of transfectants expressing chimeric CD8/ζ constructs encoding increasing COOH-terminal truncations of TCR ζ indicates that four of these mAbs recognized the region of TCR ζ chain comprising the last 29 COOH-terminal residues. Thus, this region of TCR ζ may encode an immunodominant epitope. Furthermore, one of these mAbs, G3, is capable of precipitating both non-phosphorylated and tyrosine phosphorylated TCR ζ. The G3 mAb should be useful for elucidiating the structural and signalling characteristics of the TCR ζ chain.     

Receptor-binding properties of modern human influenza viruses primarily isolated in Vero and MDCK cells and chicken embryonated eggs

To study the receptor specificity of modern human influenza H1N1 and H3N2 viruses, the analogs of natural receptors, namely sialyloligosaccharides conjugated with high molecular weight (about 1500 kDa) polyacrylamide as biotinylated and label-free probes, have been used. Viruses isolated from clinical specimens were grown in African green monkey kidney (Vero) or Madin-Darby canine kidney (MDCK) cells and chicken embryonated eggs. All Vero-derived viruses had hemagglutinin (HA) sequences indistinguishable from original viruses present in clinical samples, but HAs of three of seven tested MDCK-derived isolates had one or two amino acid substitutions. Despite these host-dependent mutations and differences in the structure of HA molecules of individual strains, all studied Vero- and MDCK-isolated viruses bound to Neu5Ac alpha2-6Galbeta1-4GlcNAc (6'SLN) essentially stronger than to Neu5Acalpha2-6Galbeta1-4Glc (6'SL). Such receptor-binding specificity has been typical for earlier isolated H1N1 human influenza viruses, but there is a new property of H3N2 viruses that has been circulating in the human population during recent years. Propagation of human viruses in chicken embryonated eggs resulted in a selection of variants with amino acid substitutions near the HA receptor-binding site, namely Gln226Arg or Asp225Gly for H1N1 viruses and Leu194Ile and Arg220Ser for H3N2 viruses. These HA mutations disturb the observed strict 6'SLN specificity of recent human influenza viruses.     

The Potential of Anti-Bullying Efforts to Prevent Academic Failure and Youth Crime. A Case Using the Olweus Bullying Prevention Program (OBPP)

Prevention Science - The effectiveness of bullying prevention programs has led to expectations that these programs could have effects beyond their primary goals. By reducing the number of victims...     

Transclival approaches for intradural pathologies: historical overview and present scenario

Neurosurgical Review - Recently, endoscopic transsphenoidal transclival approaches have been developed and their role is widely accepted for extradural pathologies. Their application to intradural...     

Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description

Neurosurgical Review - Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used...     

Patients undergoing surgery for lumbar degenerative spinal disorders favor smartphone-based objective self-assessment over paper-based patient-reported outcome measures

Background ContextSmartphone-based applications enable new prospects to monitor symptoms and assess functional outcome in patients with lumbar degenerative spinal disorders. However, little is known regarding patient acceptance and preference towards new modes of digital objective outcome assessment.PurposeTo assess patient preference of an objective smartphone-based outcome measure compared to conventional paper-based subjective methods of outcome assessment.Study designProspective observational cohort study.Patient sampleFourty-nine consecutive patients undergoing surgery for lumbar degenerative spinal disorder.Outcome measuresPatients completed a preference survey to assess different methods of outcome assessment. A 5-level Likert scale ranged from strong disagreement (2 points) over neutral (6 points) to strong agreement (10 points) was used.MethodsPatients self-determined their objective functional impairment using the 6-minute Walking Test application (6WT-app) and completed a set of paper-based patient-reported outcome measures (PROMs) before and 6 weeks after surgery. Patients were then asked to rate the methods of outcome assessment in terms of suitability, convenience, and responsiveness to their symptoms.ResultsThe majority of patients considered the 6WT-app a suitable instrument (median 8.0, interquartile range [IQR] 4.0). Patients found the 6WT more convenient (median 10.0, IQR 2.0) than the Zurich Claudication Questionnaire (ZCQ; median 8.0, IQR 4.0, p=.019) and Core Outcome Measure Index (COMI; median 8.0, IQR 4.0, p=.007). There was good agreement that the 6WT-app detects change in physical performance (8.0, IQR 4.0). 78 % of patients considered the 6WT superior in detecting differences in symptoms (vs. 22% for PROMs). Seventy-six percent of patients would select the 6WT over the other, 18% the ZCQ and 6% the COMI. Eighty-two percent of patients indicated their preference to use a smartphone app for the assessment and monitoring of their spine-related symptoms in the future.ConclusionsPatients included in this study favored the smartphone-based evaluation of objective functional impairment over paper-based PROMs. Involving patients more actively by means of digital technology may increase patient compliance and satisfaction as well as diagnostic accuracy.     

Schwannoma of the nasal septum: a case report with review of the literature

Schwannomas are neurogenic neoplasms rarely found in the sinonasal tract, where localization to the nasal septum is exceedingly rare (only 11 cases have been described in the western literature). We report the case of a 29-year-old white male with a schwannoma completely filling the left nasal fossa and arising from the bony part of the septum. A computer tomography (CT) scan and a biopsy suggestive of benign schwannoma were obtained before the lesion was removed by a degloving approach. The preoperative diagnosis of nasal septum schwannoma was confirmed. The patient is asymptomatic and without endoscopic evidence of recurrence 7 years after surgery. A review of the literature with particular emphasis on the clinical presentation, histological features, differential diagnosis and therapeutic options for such a rare lesion is included. Received: 11 June 1999 / Accepted: 10 February 2000     

Adenosine coronary vasodilation quantitative technetium 99m methoxy isobutyl isonitrile myocardial tomography in the identification and localization of coronary artery disease

Background

Exercise and dipyridamole ^99mTc-labeled methoxy isobutyl isonitrile (MIBI) myocardial scintigraphy have been widely used for the diagnosis of coronary artery disease (CAD). However, only limited data on adenosine ^99mTc-labeled MIBI cardiac imaging are currently available. This study was designed to assess the accuracy of quantitative adenosinerest ^99mTc-labeled MIBI tomography in the diagnosis and localization of CAD.

Methods and Results

Fifty-seven consecutive patients with suspected CAD who underwent coronary angiography and 22 normal volunteers were studied. All patients underwent ^99mTc-labeled MIBI tomography after administration of adenosine (140 μg/kg intravenously for 6 minutes) and at rest. A total of 171 vascular coronary territories were analyzed quantitatively. All patients with CAD (≥50% luminal stenosis) (n=55) had abnormal ^99mTc-labeled MIBI tomograms. The normalcy rate was 86% by quantitative analysis. Overall sensitivity, specificity, and diagnostic accuracy for detection of individual stenosed vessels were 84%, 87%, and 85%, respectively. In patients with one-vessel CAD (n=24), sensitivity and diagnostic accuracy in the detection of individual stenosed vessels were significantly (p<0.05) higher compared with patients with multivessel CAD (n=31). Moreover, 75% of patients with one-vessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in only one coronary artery territory, and 74% of patients with multivessel disease showed a scintigraphic pattern characterized by the presence of perfusion defects in two or more coronary artery territories. Sensitivity, specificity, and diagnostic accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=18) compared with those with previous myocardial infarction (n=39). In myocardial territories related to noninfarcted areas (n=124), sensitivity and specificity in the detection of stenosed vessels were 75% and 88%. In infarcted areas (n=47), sensitivity and specificity in the detection of stenosed vessels were 98% and 80% (differences not significant vs noninfarcted areas).

Conclusions

Adenosine-controlled coronary vasodilation combined with quantitative ^99mTc-labeled MIBI tomography is accurate for identifying patients with CAD and localizing individual stenosed coronary arteries.     

Quantitative exercise technetium-99m tetrofosmin myocardial tomography for the identification and localization of coronary artery disease

The aim of this study was to evaluate the accuracy of quantitative 1-day exercise-rest technetium-99m tetrofosmin tomography in the identification of patients with coronary artery disease (CAD) and in the detection of individual stenosed coronary vessels. Sixty-one patients with suspected CAD who underwent coronary angiography and 13 normal volunteers were studied. All patients were submitted to two i.v. injections of^99mTc-tetrofosmin, one at peak exercise (370 MBq) and the other (1110 MBq) at rest 3 h after exercise (images 15–30 min after injection for both studies). All patients with CAD (0% luminal stenosis) (n=50) had an abnormal^99mTc-tetrofosmin tomogram. Only one patient without significant coronary narrowing showed abnormal findings. Overall sensitivity, specificity and diagnostic accuracy in the detection of individual stenosed vessels were 77%, 93% and 85%, respectively. Sensitivity and diagnostic accuracy in the identification of individuals stenosed coronary vessels were significantly higher (P<0.05) in patients with single-vessel disease (n=21) than in those with multivessel disease (n=29). Sensitivity, specificity and accuracy for detecting individual diseased vessels were similar in patients without previous myocardial infarction (n=26) and in those with previous myocardial infarction (n=35). In myocardial territories related to non-infarcted areas (n=128), sensitivity and specificity in the detection of stenosed vessels were 70% and 95%, respectively. In infarcted areas (n=55), sensitivity and specificity in the detection of stenosed vessels were 85% (P=NS vs non-infarcted areas) and 75% (P<0.05 vs non-infarcted areas), respectively. Finally, sensitivity was significantly lower (P<0.05) in vascular territories supplied by vessels with moderate stenosis (50%–75%) than in those supplied by vessels with severe stenosis (>75%). The results of this study demonstrate that quantitative 1-day exercise-rest^99mTc-tetrofosmin single-photon emission tomographic imaging is a suitable and accurate technique to identify patients with CAD and to detect individual stenosed coronary vessels.