Binding of Mycoplasma arthritidis-derived mitogen to human MHC class II molecules via its N terminus is modulated by invariant chain expression and its C terminus is required for T cell activation

Mycoplasma arthritidis-derived mitogen (MAM) is considered to be a member of the super-antigen family despite the fact that there is no evidence until now indicating its binding to MHC class II molecules. To demonstrate its direct binding and to determine the regions involved in MHC class II and TCR interactions, we generated a recombinant wild-type and two truncated forms of the MAM protein. Data obtained in the course of the present investigation show that MAM binds specifically and significantly to human MHC class II molecules. Evidence is also provided that MAM bears two distinct binding regions: one is located within its N terminus and interacts with MHC class II molecules, while the second region which is located in its C terminus mediates its recognition by the TCR. Association of the MHC class II-associated invariant chain peptide with the peptide binding groove on the cell surface completely abolished MAM binding and presentation. This inhibitory effect is restored by the expression of HLA-DM molecules, suggesting that the nature of the peptide within the binding groove and/or the stability of the MHC class II molecules on the cell surface may modulate MAM/MHC class II interactions.     

Mutagenicity of bisphenol A (4,4'-isopropylidenediphenol) in vitro: effects of nitrosylation

Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.     

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in onset ages above 55 years, with one segregating in an autosomal dominant family with mean onset age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with onset age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.      

Plasma concentrations of complement-activation complexes correlate with disease activity in patients diagnosed with isolated central nervous system vasculitis

Isolated central nervous system (CNS) vasculitis is rare medium- sized vessel disease limited to intracerebral vessels. The two most common symptoms of this inflammatory disorder observed at entry to a hospital are headaches and mild memory deficits. Further progression of this disease may result in focal neurologic alterations and seizures. Currently, the most common laboratory abnormality noted is an elevated erythrocyte sedimentation rate. The complement (C) system is known to play a role in many inflammatory processes; it may also be involved in CNS vasculitis. In this longitudinal study of patients with CNS vasculitis, we detected C activation by highly sensitive and specific assays that are capable of identifying breakdown products formed after C activation: C3a des arg, C4a des arg, C5a des arg, C1rC1s-C1-inhibitor complex, and terminal C complex (C5b-9). We present two cases of documented CNS vasculitis in which serial measurements of these C-activation products correlate with disease activity. Our results indicate that a temporal association exists between C activation and the clinical presentation of CNS vasculitis. We conclude that physicians should monitor C-activation by-products in plasma when they attempt to follow the clinical course of CNS vasculitis.     

Why did persons invited to train in cardiopulmonary resuscitation not do so?

All citizens (N = 22066) aged 16 to 65 of a medium-sized Belgiantown were personally invited to CPR training sessions held intheir neighbourhood. 1152 responded by attending a trainingsession. Those who did not so respond were surveyed (randomsample N=600) for reasons of their not coming. The sample fittedwell with census data for gender, age and suburb location butnot for job, because retired persons and women at home wereover represented. 123 persons did not want to answer the questions. 116 personssaid they were already trained in CPR, 276 said they would accepton a future occasion and 82 said they would not. Three personsdid not answer this question. There was no discrimination for job, gender and suburb locationbetween those who did and did not accept a future training opportunity,nor was the existence of a heart patient among relatives. Theolder the person, the less inclined was that person to participatein CPR training (age effect x² = 17.17, d.f. = 9, P<0.05).The 276 who accepted future training, chose their workplace(221) and/or their social meeting place (club etc.) as the placewhere this future training should be held. We suggest that CPR training is well accepted and that the trainingopportunities should be given at places of work and social gatherings.     

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.     

Fusarium endocarditis involving aortic valve following coronary artery surgery

This article describes a case of infective aortic valve endocarditisdue to Fusarium oxysporum occurring 4 years after coronary arterybypass grafting. It is the first reported case of endocarditiscaused by Fusarium.     

USE OF POST-TETANIC COUNT IN ASSESSMENT OF A REPETITIVE VECURONIUM-INDUCED NEUROMUSCULAR BLOCK

In order to evaluate the use of the post-tetanic count (PTC)method during repetitive administration of vecuronium, we studied20 patients allocated randomly to one of two groups: 10 patientsreceived droperidol-fentanyl anaesthesia (control group); 10other patients were given droperidol-fentanyl anaesthesia modifiedsubsequently by addition of 0.5% isoflurane (isoflurane group).Before tracheal intubation, a bolus dose of vecuronium 0.08mg kg^–1 was given i. v. followed by repeated doses of0.03 mg kg^–1. The twitch response of adductor polliciswas recorded after supramaximal stimulation of the ulnar nerveat the wrist using a Myograph 2000 neuromuscular transmissionanalyser. In the control group, a close correlation was foundbetween PTC and time to first reaction to train-of-four (TOF)nerve stimulation. This relationship was unchanged when comparingthe bolus dose and each of eight consecutive maintenance doses.Further, the degree and the duration of intense block were unchangedafter each of the eight maintenance doses. In the isofluranegroup, the relationship between PTC and time to first reactionto TOF stimulation remained unchanged after addition of isoflurane.However, isoflurane caused a significant prolongation of theduration of intense block and a corresponding lower PTC in allpatients. We conclude that PTC is a reliable method to evaluateintense neuromuscular block caused by vecuronium, even afterrepetitive administration of the drug and in combination with0.5% isoflurane. Presented in part at the annual meeting of the American Societyof Anesthesiologists, San Francisco, October 1988.