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.     

Antiphospholipid antibodies and the outcome of pregnancy after the first in-vitro fertilization and embryo transfer cycle

Increased antiphospholipid antibody prevalence has been demonstrated by a number of recent studies in in-vitro fertilization (IVF) patients but the potential effects of antiphospholipid antibodies on the different components of the reproductive process and the consideration of whether to test IVF patients for antiphospholipid antibodies are controversial. The present study was undertaken to investigate the possible association between the presence of circulating antiphospholipid antibodies (namely the lupus anticoagulant and anticardiolipin antibodies), among a series of 21 consecutive IVF patients having a clinical spontaneous abortion after their first embryo transfer. As a control group (n=42), the nearest IVF cycle resulting in an ongoing pregnancy before and after each miscarried IVF cycle (i.e. the closest cycles in temporal relationship to the index cycle) was used. One patient (4.8%) in the study group and two women (4.8%) among controls were seropositive for antiphospholipid antibodies. These low and similar seropositivity rates found in the two groups studied lead us to conclude that antiphospholipid antibodies testing in IVF patients should be considered only in those women having repeated failures of implantation/clinical abortion after embryo transfer but not in an infertile general population reaching an IVF programme.      

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in- vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.      

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

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.     

Biological resurfacing of the knee: a review of surgical management

Lesions of the articular surfaces of the knee have been managed by various techniques over the last 50 years. Surgical management has involved: excising the damaged area, refashioning the underlying bone to produce a fibrous response, and introducing allograft, autograft and synthetic materials to encourage a repair matrix. The techniques and their pitfalls are reviewed and discussed, and suggestions made as to the direction of future studies for the repair of osteochondral lesions in the painful knee.