CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells

Lyme disease is a common multisystem disease caused by infection with a tick‐transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL‐II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL‐II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b‐BbGL‐II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL‐II‐like molecules using tetramers and activation assays revealed a concomitant response to CD1b‐expressing APCs in absence of BbGL‐II. Further, among all major classes of self‐lipid tested, BbGL‐II responsive TCRs show strong cross‐reactivity to diacylglycerol, a self‐lipid antigen with structural similarities to BbGL‐II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross‐reactive CD1b‐restricted T cell responses to bacterial and self‐antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross‐reactive T cells.     

Relationship between loss of sight and mortality in diabetics with retinopathy (a retrospective study over the terminal 5 years) (author's transl)]

1642 diabetics with retinopathy were controlled at half-yearly intervals over 4 to 10 years (6 years on average) using fundus photography, fluoresceinangiography and measurement of visual acuity. 83 of these patients died and the data documented in 43 patients over a mean period of 5.2 years prior to death allowed a retrospective evaluation of the clinical findings and therapeutic results. 27 patients had undergone bilateral and 16 unilateral photocoagulation at the beginning of the observation period. 9 patients were blind already at the outset. Of 13 patients who became blind during the observation period 10 had not undergone photocoagulation of the affected eye. The time span between blindness and death was shorter (1.5 years) in the 3 patients (5 eyes) who had undergone photocoagulation than in the untreated diabetics (4.3 years). All 23 patients in whom the initial visual acuity was maintained had undergone photocoagulation. Presence of florid diabetic retinopathy or nephropathy adversely influenced the results of photocoagulation.     

A novel human autoantigen,endothelial cell growth factor,is a target of T and B cell responses in patients with Lyme disease

Objective

Autoantigen presentation by HLA–DR molecules is thought to be a central component of many autoimmune diseases, but identifying disease‐relevant autoantigens has been a difficult challenge. In this study we aimed to identify autoantigens in patients with antibiotic‐refractory Lyme arthritis, in which infection‐induced autoimmunity is thought to play an important role.

Methods

Using tandem mass spectrometry, naturally presented HLA–DR self peptides from a patient's synovium were identified, synthesized, and reacted with his peripheral blood mononuclear cells (PBMCs). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patient cells or sera.

Results

Of 120 HLA–DR–presented self peptides identified from one patient, one peptide derived from endothelial cell growth factor (ECGF) caused his PBMCs to proliferate. T and B cell responses to ECGF occurred systemically in ∼10–30% of patients with early or late manifestations of Lyme disease, primarily in those with refractory arthritis–associated HLA–DR alleles, such as DRB1*0101 and 0401. Compared with patients with antibiotic‐responsive arthritis, those with antibiotic‐refractory arthritis had significantly higher concentrations of ECGF in synovial fluid (P < 0.0001) and more often had ECGF antibody reactivity. Among non–antibiotic‐treated historical patients who developed arthritis, 26% had ECGF reactivity, which often developed before the onset of arthritis and was associated with significantly longer courses of arthritis.

Conclusion

T and B cell responses to ECGF occur in a subset of patients with Lyme disease, particularly in those with antibiotic‐refractory arthritis, providing the first direct evidence of autoimmune T and B cell responses in this illness.

     

Cataract extraction with multifocal intraocular lens implantation: clinical, functional, and quality-of-life outcomes. Multicenter clinical trial in Germany and Austria

PURPOSE: To compare bilateral implantation of a multifocal intraocular lens (IOL) versus a monofocal lens with respect to visual function, patient satisfaction, and quality of life. SETTING: Seven clinical sites in Germany and 1 site in Austria. METHODS: A prospective randomized masked clinical trial included 124 randomly assigned bilateral pseudophakic individuals, 64 of whom had bilateral implantation of an Array(R) foldable multifocal IOL (model SA-40N, Allergan) and 60 of whom had bilateral implantation of an AMO(R)PhacoFlex II(R) silicone monofocal IOL (model SI-40NB). Clinical data included binocular uncorrected and corrected distance and near visual acuities, complications, adverse events, and reports of halos and glare. Quality-of-life data were collected on 3 occasions using the modified Cataract TyPE Specification instrument. The functional status of the 2 groups was compared from baseline to final postoperative interview. RESULTS: Three months after surgery, a higher proportion in the Array group achieved a Jaeger value of J3 (20/40 Snellen) or better uncorrected binocular near visual acuity and 0.5 (20/40) or better distance-corrected binocular near visual acuity than in the monofocal groups (97% versus 68% and 95% versus 59%, respectively; P <.001). A higher proportion in the multifocal group achieved both 0.5 (20/40) and J3 or better uncorrected binocular distance and near visual acuities (97% versus 66%; P <.001). Those in the Array group were more likely than those in the monofocal group to never wear glasses overall (41% versus 12%; P <.001). Multifocal patients rated their vision without glasses better overall, at near and at intermediate distances (P <.05), and demonstrated better visual function for near tasks and social activities. CONCLUSIONS: Those who had bilateral implantation of the Array multifocal IOL obtained better uncorrected and distance-corrected near visual acuities and reported better overall vision, less limitation in visual function, and less spectacle dependency than patients with bilateral monofocal IOLs.     

Microcontroller based fibre-optic visual presentation system for multisensory neuroimaging

Presenting visual stimuli in physical 3D space during fMRI experiments carries significant technical challenges. Certain types of multisensory visuotactile experiments and visuomotor tasks require presentation of visual stimuli in peripersonal space, which cannot be accommodated by ordinary projection screens or binocular goggles. However, light points produced by a group of LEDs can be transmitted through fibre-optic cables and positioned anywhere inside the MRI scanner. Here we describe the design and implementation of a microcontroller-based programmable digital device for controlling fibre-optically transmitted LED lights from a PC. The main feature of this device is the ability to independently control the colour, brightness, and timing of each LED. Moreover, the device was designed in a modular and extensible way, which enables easy adaptation for various experimental paradigms. The device was tested and validated in three fMRI experiments involving basic visual perception, a simple colour discrimination task, and a blocked multisensory visuo-tactile task. The results revealed significant lateralized activation in occipital cortex of all participants, a reliable response in ventral occipital areas to colour stimuli elicited by the device, and strong activations in multisensory brain regions in the multisensory task. Overall, these findings confirm the suitability of this device for presenting complex fibre-optic visual and cross-modal stimuli inside the scanner.     

In inverted papillomas HPV more likely represents incidental colonization than an etiological factor

Inverted papillomas (IPs) are the most frequent type of sinonasal papillomas. These benign but destructive lesions are known for their high recurrence rate, probably due to incomplete excision. Our aim was to investigate the frequency of human papillomavirus (HPV) infection in patients with IPs and in IPs associated with squamous cell carcinoma (IPsSCC) and to compare it with the frequency of HPV infections in the control group. The influence of HPV infection on the malignant alteration and recurrence rate of IPs was also evaluated. Paraffin-embedded tissue samples from 68 patients with sinonasal IPs and 5 patients with IPsSCC were analyzed in this retrospective study. The control group consisted of 47 patients who had undergone septoplasty or mucotomy of the inferior turbinate. PCR amplification with consensus primer sets was performed to detect alpha-HPVs, and direct sequencing of the PCR products with the same primers was used to determine the HPV genotypes in the samples. We detected HPV DNA in 20 (30.3%) patients with IPs, in 3 (60%) patients with IPsSCC, and in 6 (13%) patients from the control group. The frequency of HPV infection in the study group was statistically significantly higher (p = 0.032) than in the control group. The presence of HPV DNA was not a statistically significant predictor of the recurrence of IPs (p = 0.745) nor was it a statistically significant risk factor for associated SCC (p = 0.32). Since HPV type 11 was the predominant genotype in the IPs, IPsSCC, and in the control cases, we presume that HPV infection may represent incidental colonization rather than being an important etiological factor of IPs.     

Combination of lung ultrasound (a comet-tail sign) and N-terminal pro-brain natriuretic peptide in differentiating acute heart failure from chronic obstructive pulmonary disease and asthma as cause of acute dyspnea in prehospital emergency setting

Introduction  

We studied the diagnostic accuracy of bedside lung ultrasound (the presence of a comet-tail sign), N-terminal pro-brain natriuretic peptide (NT-proBNP) and clinical assessment (according to the modified Boston criteria) in differentiating heart failure (HF)-related acute dyspnea from pulmonary (chronic obstructive pulmonary disease (COPD)/asthma)-related acute dyspnea in the prehospital setting.     

Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach

Background

Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients.

Materials and methods.

We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM.

Results

We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM.

Conclusions

Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.     

Supporting bereaved parents: practical steps in providing compassionate perinatal and neonatal end-of-life care. A North American perspective

Providing compassionate bereavement support challenges care-givers in perinatal medicine. A practical and consistent approach tailored to individual families may increase the care-giver's ability to relieve parental grief. This approach includes: (1) clear and consistent communication compassionately delivered; (2) shared decision-making; (3) physical and emotional support; and (4) follow-up medical, psychological and social care. Challenges to providing comprehensive end-of-life care include care-giver comfort, consistency of care, cultural and legal barriers, and lack of adequate training.