Derivation of HLA-A11/Kb transgenic mice: functional CTL repertoire and recognition of human A11-restricted CTL epitopes

Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.     

Identifying twin gestations at low risk for preterm birth with a transvaginal ultrasonographic cervical measurement at 24 to 26 weeks' gestation

OBJECTIVE: Because twins are a high-risk group for preterm birth, many clinicians routinely use prophylactic interventions such as home bed rest, hospital bed rest, oral tocolytics, or home uterine activity monitoring to prevent preterm delivery. We sought to identify twin gestations at low risk for spontaneous preterm birth with transvaginal ultrasonography of the cervix to avoid the unnecessary use of prophylactic interventions in these pregnancies. STUDY DESIGN: We measured cervical length at 24 to 26 weeks' gestation by transvaginal ultrasonography in women with twin gestations referred to our prematurity prevention clinic. Each delivery was classified as (1) spontaneous preterm birth < 34 weeks' gestation, (2) delivery at > or = 34 weeks' gestation with intervention, or (3) delivery at > or = 34 weeks' gestation without intervention. Intervention included strict bed rest at home or in the hospital, either parenteral or oral tocolysis, or both, or home uterine activity monitoring. Indicated preterm deliveries and patients with cerclage were excluded from this analysis. The ability of transvaginal cervical length to predict women who would deliver at > or = 34 weeks without intervention was evaluated. A cervical length of 35 mm was chosen by scatter diagram as the best cutoff to discriminate between the group delivered at term without intervention and the other two groups. RESULTS: Of 85 women with twin gestations who underwent ultrasonographic cervical length measurements at 24 to 26 weeks' gestation, 17 had spontaneous preterm birth at < 34 weeks, 23 were delivered at > or = 34 weeks but required intervention, and 45 were delivered at > or = 34 weeks without intervention. The mean cervical length for those delivered at > or = 34 weeks' gestation without intervention (36.4 +/- 5.8 mm) was significantly greater (p < 0.0001) than the mean for those delivered preterm (27.4 +/- 8.5) and those delivered at > or = 34 weeks' gestation who required intervention (27.7 +/- 10.5 mm). The sensitivity, specificity, and positive and negative predictive values of a cervical length > 35 mm for predicting delivery at > or = 34 weeks' gestation are 49%, 94%, 97%, and 31%, respectively. CONCLUSION: A transvaginal ultrasonographic measurement of the cervix of > 35 mm at 24 to 26 weeks in twin gestations can identify patients who are at low risk for delivery before 34 weeks' gestation.     

Computing eigenvalue bounds for iterative subspace matrix methods

A procedure is presented for the computation of bounds to eigenvalues of the generalized hermitian eigenvalue problem and to the standard hermitian eigenvalue problem. This procedure is applicable to iterative subspace eigenvalue methods and to both outer and inner eigenvalues. The Ritz values and their corresponding residual norms, all of which are computable quantities, are needed by the procedure. Knowledge of the exact eigenvalues is not needed by the procedure, but it must be known that the computed Ritz values are isolated from exact eigenvalues outside of the Ritz spectrum and that there are no skipped eigenvalues within the Ritz spectrum range. A multipass refinement procedure is described to compute the bounds for each Ritz value. This procedure requires O(m) effort where m is the subspace dimension for each pass.     

Nuclear magnetic resonance analysis of solution conformations in C4-V3 hybrid peptides derived from human immunodeficiency virus (HIV) type 1 gp120: relation to specificity of peptide-induced anti-HIV neutralizing antibodies

Immunogenic peptides containing epitopes of the gp120 C4 and V3 regions from human immunodeficiency virus strains MN and EV91 have been studied by nuclear magnetic resonance and molecular modeling and used as immunogens in rhesus monkeys. The results, combined with those for other peptides, suggest a correlation between solution conformation and immunologic cross-reactivity.     

A view from the family: years after a loved one has died of ovarian cancer

BACKGROUND: Macrosclerotherapy in combination with compression has proven to be safe and effective in the treatment of varicose veins. Local compression is increased by pads, according to Laplace law. Firm rolls of cotton wool are fixed over the course of the entire vein to increase local compression and to reduce complications. Additional compression is given by a combination of a class I (daytime and nighttime) and class II (daytime only) medical compression hosiery. PURPOSE: To evaluate the effectiveness and side effects of sclerocompression therapy with cotton wool rolls in combination with medical compression hosiery. METHOD: Prospective study with 100 patients (120 legs) with primary varicose veins, which are treated with polidocanol as sclerosant with the empty vein technique. Immediately after the injection, a long cotton wool roll is placed over the entire vein and fixed. Additional compression is obtained with class I and class II medical compression hosiery. The interface pressure on the skin, just under the cotton wool roll, is measured on 12 legs with the aid of an interface pressure measuring instrument (Oxford Pressure Monitor). RESULTS: Good sclerosing results are obtained in all patients. Side effects are classified as early and late. In 16 patients, minor side effects which needed no treatment are observed. In only 3 cases (2.5%), intravascular blood clots (2) and phlebitis (1) needed incision and expression. The mean interface pressure of all measuring sensors under the cotton wool roll is 84 mm/Hg (68 to 122 mm/Hg). CONCLUSION: This study proves the high effectiveness of a cotton wool roll compression right at the place of treatment. By using these long cotton wool compression rolls, the compression part of sclerocompression therapy becomes more effective and much easier to perform.     

Entorhinal cortex of aged subjects with Down''s syndrome shows severe neuronal loss caused by neurofibrillary pathology

OBJECTIVE: To examine directly the extent to which ICD-10 hyperkinetic disorder and DSM-IV attention-deficit/hyperactivity disorder (ADHD) identify the same children with the same difficulties. METHOD: Participants were children referred for symptoms of overactivity, inattention, and impulsivity, and a normal control group. Diagnostic criteria for ICD-10 hyperkinetic disorder and DSM-IV ADHD were applied retrospectively. Four groups were identified: hyperkinetic disorder and ADHD (n = 21), ADHD only (n = 22), clinic control (n = 15), and normal control (n = 19). The groups were compared on measures reflecting the central characteristics of ADHD, neurodevelopmental functioning, academic and cognitive functioning, and the presence of conduct problems. RESULTS: There is some evidence of increased symptom severity in the combined diagnostic group. Few differences emerged on measures of neurodevelopmental, academic, and cognitive functioning. Rates of conduct disturbance were similar in both ADHD groups. CONCLUSIONS: DSM-IV criteria identify a broader group of children than those identified by ICD-10. However, there is substantial overlap between the groups formed with these different criteria.