Relationship between peptide binding and T cell epitope selection: a study with subtypes of HLA-B27

The effect of HLA-B27 polymorphism on antigen presentation was analysed by comparing the binding of three Epstein-Barr virus-derived peptide epitopes to HLA-B27 subtypes with their immunogenicity and antigenicity in the context of these subtypes. The effect of altering the major anchor residue Arg2 on binding or on recognition by peptide-specific cytotoxic T lymphocytes (CTL) was also examined. The three peptides bound significantly to all the B*2701-B*2706 subtypes. This did not correlate with the peptides being immunogenic or recognized by specific CTL in the context of only particular subtypes. In addition, of the three viral epitopes tested, those that were immunogenic in B*2702- or B*2705-restricted responses bound to these subtypes less efficiently than one peptide that was immunogenic only in the B*2704 context. Thus, among several potentially immunogenic peptides from the same virus, the antiviral response is not necessarily directed against the one that binds best to the restricting subtype. These results indicate that HLA- B27 polymorphism influences antigen presentation in ways other than simply peptide affinity. Synthetic analogues lacking the canonical Arg2 motif of HLA-B27-bound peptides, even when binding much worse to the restricting subtype, were recognized equally by CTL specific for the parental peptide. This indicates that Arg2 is not required to maintain the structure of the epitope. The implications of these results for pathogenetic models of HLA-B27-associated disease are discussed.      

Calcium antagonist properties of the bisbenzylisoquinoline alkaloid cycleanine

Summary— The alkaloid cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octahydro-5,6,17,18-tetramethoxy-1,13-dimethyl-8,11: 20,23-dietheno-1H,12H [1,10]dioxacyclooctadecino[2,3,4-ij: 11,12,13-i'j']diisoquinoline) was extracted from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and smooth muscle preparations were studied and compared to those of nifedipine (1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit aortic rings with higher potency than nifedipine. IC50s for cycleanine and nifedipine were 0.8 and 7·10⁻⁹ M respectively. Cycleanine had minor effects on the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and nifedipine also depressed the contraction of rat ventricular preparations but with lower potency (IC50 = 3 and 0.03·10⁻⁶ M respectively). Action potential duration of rat right ventricular strips was decreased by both compounds. L-type Ca-current (I_CaL) of single rat ventricular cardiomyocytes was inhibited by cycleanine in a voltage- and frequency-dependent manner. With a higher potency nifedipine inhibited I_CaL in a tonic and almost frequency-independent manner. The results suggest that cycleanine can act as a potent vascular selective Ca-antagonist.     

Adolescent day program: a two year retrospective review

The place of a psychiatric day treatment program within the spectrum of necessary treatment options is noted in the literature review. A established day program is described with some characteristics of 97 youths attending the program over a two year period. The authors highlight those characteristics which correlate with benefits derived from program attendance.     

Choice of urine sample predictive of microalbuminuria in patients with insulin-dependent diabetes mellitus

Twenty-four-hour, four-hour (8 to 12 am), and overnight urine collections were examined for their ability to detect microalbuminuria in 292 patients with insulin-dependent diabetes mellitus (IDDM). Albumin excretion rate (AER) was measured and also estimated from the product of the urinary albumin/creatinine ratio (A/C) and the calculated 24-hour creatinine excretion. The fractional excretion of albumin (FEA) was also determined in aliquots from each urine sample. The correlation coefficients between measured 24-hour AER and estimated AER were 0.940 and 0.956 for four-hour and overnight collections, respectively (significance of each correlation, P less than 0.001). There was no advantage in using the FEA over the A/C ratio in predicting measured AER. Urinary A/C ratios (mg/mg) between 0.03 and 0.31 in the four-hour collections were highly predictive of microalbuminuria and of measured AER in the 24-hour collections: AER24-h (microgram/min/1.73 m2) = 2.74 + 0.870 x A/C4-h (all log10 values). In a subgroup of 175 patients having all three collections validated, 34 (20%) had microalbuminuria defined as AER 20 to 200 micrograms/min/1.73 m2 in at least two of the three samples and 44 (25%) had overt nephropathy (greater than 200 micrograms/min/1.73 m2). The ability of the AER in one urine collection to predict microalbuminuria in at least one of the other two collections was assessed in these 175 patients. Compared with the overnight urine collection, the four-hour collection had greater sensitivity while affording similar specificity and positive predictive value. Based on these data, the A/C ratio from a morning urine sample following initial AM voiding would seem adequate for the detection and monitoring of microalbuminuria in patients with IDDM.     

Videodensitometric quantitation of stenosis: in vitro and in vivo validation

Percentage of stenosis of a vascular lumen was quantitated using a digital subtraction angiography system with videodensitometric analysis. To validate the algorithm and methods, we used precisely drilled Lucite rods of three inner diameters and various reduced diameters to give known luminal reduction. Both in vitro and in vivo results of stenosis measurements resulted in an excellent correlation between actual and measured values (correlation coefficient greater than 0.9 for all trials). Consistent underestimation of stenosis of about 5% was attributed to the various image degradations inherent with the imaging procedure and equipment. Errors were greatest with midrange stenoses and less at the extremes of the lesion values. An insufficient signal-to-noise ratio was caused by low photon flux and/or low contrast material concentration and overlying vasculature filled with contrast material. Overall, the videodensitometric technique is accurate, easy to implement, objective, and relatively free of errors associated with the geometric/edge detection method.     

Anti-cardiolipin antibodies in sexual partners of recurrent aborters

The presence of anti-cardiolipin antibodies (aCL) in women is an established risk factor for fetal loss, but these autoantibodies had not previously been investigated in the male partners of recurrent aborters. The prevalence of aCL in 144 male partners of couples with a history of recurrent miscarriage was 4.2%, which compares with 2.8% for 177 female partners of such couples, 5.9% of 254 blood donors (128 male, 126 female) and 0% of 74 women of good obstetric history sampled in the puerperium. In recurrent miscarriage couples, the presence of aCL in the women was associated with a poorer history and outlook, but these associations were not evident in couples where the male partner had aCL. The aCL of male partners also differed from those of their spouses in being less likely to show higher activity towards phosphatidylserine than towards phosphatidylcholine. A particular sub- population of aCL may be strongly represented in the male partners, the clinical significance of which remains to be established.