An autoimmunity odyssey: how autoreactive T cells infiltrate into the CNS

Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), a human autoimmune disease. To explore how EAE and ultimately MS is induced, autoantigen-specific T cells were established, were labeled with fluorescent protein by retroviral gene transfer, and were tracked in vivo after adoptive transfer. Intravital imaging with two-photon microscopy was used to record the entire entry process of autoreactive T cells into the CNS: a small number of T cells first appear in the CNS leptomeninges before onset of EAE, and crawl on the intraluminal surface of blood vessels, which is integrin α4 and αL dependent. After extravasation, the T cells continue into the perivascular space, meeting local antigen-presenting cells (APCs), which present endogenous antigens. This interaction activates the T cells and guides them to penetrate the CNS parenchyma. As the local APCs in the CNS are not saturated with endogenous antigens, exogenous antigens stimulate the autoreactive T cells more strongly and, as a result, exacerbate the clinical outcome. Currently, we are attempting to visualize T-cell activation in vivo in both rat T-cell-mediated EAE and mouse spontaneous EAE models.     

Effects of Efflux Pump Inhibitors on Erythromycin, Ciprofloxacin, and Tetracycline Resistance in Campylobacter spp. Isolates

The aim was to assess the potency of the efflux pump inhibitors (EPIs) phenylalanine-arginine ?-naphthylamide (PA?N) and 1-(1-naphthylmethyl)-piperazine (NMP) and the putative natural EPI phenolic (-)-epigallocatechin gallate (EGCG) for the reversal of erythromycin, ciprofloxacin, and tetracycline resistance in Campylobacter jejuni and Campylobacter coli isolates. We investigated target mutations and resistant genes involved in erythromycin and tetracycline resistance and determined the roles of the bacterial drug efflux systems (cmeB, cmeF, and cmeR) in antimicrobial resistance. Our data show that most of the high-level erythromycin resistance and all of the tetracycline resistance can be explained through mutations in 23S rRNA and the presence of the tetO gene, respectively. The EPIs show the ability to partly reverse drug resistance in these Campylobacter isolates. Based on a fourfold or greater reduction in the erythromycin minimal inhibitory concentration (MIC), PA?N and NMP had clear effects in almost of all of the isolates tested. PA?N had a highly selective action on the ciprofloxacin and tetracycline MICs. Inactivation of cmeB increased susceptibility to all of the antimicrobials tested, whereas inactivation of cmeF and cmeR had no effects. A notable decrease in resistance to erythromycin and ciprofloxacin in the presence of subinhibitory concentrations of EGCG demonstrates the resistance-modifying activities of this natural EPI, and indicates its potential use in the control of Campylobacter spp. in the food chain.     

Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo

Background

Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association.

Methods

A comprehensive search was conducted to identify all case-control studies of COX-2 rs2745557 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Statistical analyses were performed by Review Manage, version 5.0 and Stata 10.0.

Results

A total of 8 available studies were considered in the present meta-analysis, with 11356 patients and 11641 controls for rs2745557. When all groups were pooled, there was no evidence that rs2745557 had significant association with PCa under co-dominant, recessive, over-dominant, and allelic models. However, our analysis suggested that rs2745557 was associated with a lower PCa risk under dominant model in overall population (OR = 0.85, 95%CI = 0.74-0.97, P = 0.02). When stratifying for race, there was a significant association between rs2745557 polymorphism and lower PCa risk in dominant model comparison in the subgroup of Caucasians (OR = 0.86, 95%CI = 0.75-0.99, P = 0.04), but not in co-dominant, recessive, over-dominant and allelic comparisons.

Conclusion

Based on our meta-analysis, COX-2 rs2745557 was associated with a lower PCa risk under dominant model in Caucasians.     

Slaying the dragon myth: an ethnographic study of receptionists in UK general practice

Background

General practice receptionists fulfil an essential role in UK primary care, shaping patient access to health professionals. They are often portrayed as powerful ‘gatekeepers’. Existing literature and management initiatives advocate more training to improve their performance and, consequently, the patient experience.

Aim

To explore the complexity of the role of general practice receptionists by considering the wider practice context in which they work.

Design and setting

Ethnographic observation in seven urban general practices in the north-west of England.

Method

Seven researchers conducted 200 hours of ethnographic observation, predominantly in the reception areas of each practice. Forty-five receptionists were involved in the study and were asked about their work as they carried out their activities. Observational notes were taken. Analysis involved ascribing codes to incidents considered relevant to the role and organising these into related clusters.

Results

Receptionists were faced with the difficult task of prioritising patients, despite having little time, information, and training. They felt responsible for protecting those patients who were most vulnerable, however this was sometimes made difficult by protocols set by the GPs and by patients trying to ‘play’ the system.

Conclusion

Framing the receptionist–patient encounter as one between the ‘powerful’ and the ‘vulnerable’ gets in the way of fully understanding the complex tasks receptionists perform and the contradictions that are inherent in their role. Calls for more training, without reflective attention to practice dynamics, risk failing to address systemic problems, portraying them instead as individual failings.     

Distribution of KIR genes in the Croatian population

The KIR locus with genes involved in immune processes is among the most polymorphic and structurally diverse human loci. KIR genes encode activating and inhibitory receptors that differ in specificity for HLA class I ligands and signaling potential. These receptors are expressed principally by natural killer (NK) cells and subpopulations of T cells. This study represents the first report of the distribution of KIR genes, KIR genotypes and KIR/HLA pairs in 121 unrelated healthy Croatian individuals. Twenty-three different genotypes were observed in the Croatian population and all 16 KIR genes known to date were found. The most frequent KIR genotype was the AA genotype. All individuals had at least one inhibitory KIR/HLA pair with the majority of individuals with three inhibitory KIR/HLA pairs. The most frequent KIR/HLA pair was the KIR2DL3/C1 group. Our results demonstrated the similarity of the Croatian population’s KIR repertoire with other Caucasian populations reported so far.     

Advances in laryngeal imaging

Imaging and image analysis became an important issue in laryngeal diagnostics. Various techniques, such as videostroboscopy, videokymography, digital kymograpgy, or ultrasonography are available and are used in research and clinical practice. This paper reviews recent advances in imaging for laryngeal diagnostics.     

Verbrühung – und was macht man da?

Ohne Zusammenfassung     

Comparison of the influence of thyroglobulin antibodies on serum thyroglobulin values from two different immunoassays in post surgical differentiated thyroid carcinoma patients

Measurement of serum thyroglobulin (Tg) is a highly specific test in the management of patients with differentiated thyroid cancer (DTC) after surgical treatment. The aim of our study was to evaluate and compare Tg levels in these patients found by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) and to assess the influence of Tg antibodies (TgAbs) on the values obtained for Tg concentration. Both Tg and TgAb were determined postoperatively in the serum of 71 DTC patients using RIA Tg‐PEG (INEP) and Tg IRMA (CIS) for Tg, together with TgAb (CIS) for circulating endogenous anti‐TgAbs. The obtained concentrations were evaluated statistically. We found a significant difference of Tg concentrations between paired samples from the IRMA and RIA, although the intermethod comparison yielded satisfactory concordance of the twoassays (Spearman correlation coefficient ?0.792). Positive TgAb was found in 28.2% of the serum samples analyzed. Spearman rank correlation analysis revealed a significant negative relationship between serum TgAb and Tg level measured by IRMA (P=0.02), but not by RIA (P=0.417). On the other hand, our clinical data revealed that 1/18 and 3/18 patients with proven lymph node metastasis had Tg values below the detection limit by RIA and IRMA assay, respectively. Their sera were TgAb positive. We concluded that RIA was less prone to influence of TgAb than IRMA. As the presence of TgAbs may interfere in Tg measurement irrespective of the method selected for determination, this should be considered during the clinical management of these patients. J. Clin. Lab. Anal. 23:341–346, 2009. © 2009 Wiley‐Liss, Inc.     

Commercial rodent feed as an occasional cause of morbidity and mortality in a rat breeding colony

In the last fifteen years there were several feed-related outbreaks of morbidity and mortality in the Institute's breeding colony of Wistar rats. The last event took place in April 1999, one month after the use of a new supply of the usual standard rodent feed. Animals did not thrive and manifested generalised oedema, hypoalbuminaemia, elevated liver enzymes, and high mortality. The effect of feed was assessed first by feeding a group of sick females during 14 days with either suspected feed (A-March) or with the earlier supply of feed (A-January) of the same producer. Then a group of healthy male rats Y59 from another breeding colony was fed either suspected feed (A-March) or feed from another producer (feed B). Although neither chemical nor microbiological deviation in feed analysis had been detected, decreased consumption and slower body weight gain in all animals fed with feed A-March suggested an association between this batch of feed and the increased morbidity in those animals. Eventually, the entire rat colony was put down and replaced with a new breed which was given a new brand of feed.