Mutations in MHC class II dimer of dimers contact residues: effects on antigen presentation

The recent solutions of the MHC class II crystal structure reveal dimerization of the alphabeta heterodimers. These dimer of dimers structures may also exist either on resting cells or after engagement by TCR, and may be involved in B cell signaling and up-regulation of co-stimulatory molecules such as B7 which facilitate T cell activation. By combining crystallographic data on HLA-DR1 with the sequence of murine I-Ak and refining the resulting structure through energy minimization calculations, we have predicted the contact amino acids expected to stabilize the I-Ak dimer of dimers structure. As in HLA-DR1, three salt bridges in I-Ak (D alpha62-Hbeta112, H alpha181-E beta163, E alpha183-Hbeta113) appear to provide the main interaction. Guided by this structural data, we prepared 45 B cell transfectants representing 20 different class II mutation phenotypes in the contact region containing these salt bridges. We examined their abilities to activate three T cell hybrids. Antigen-specific h4Ly50.5 cells were not greatly affected by changes in the dimer of dimer contact residues. In contrast, autoreactive C8.A3 T cells were very sensitive to changes in this region but presentation of class II of many mutation phenotypes could be rescued by treatments that up-regulate B7-1. The alloreactive hybridoma 2H40.2.5 was less sensitive to changes in the contact residues. A simple model was developed that summarizes the effects of the mutations for the T cells tested. Mutations at D alpha162, E alpha183, H alpha181 and Rbeta106 had the largest negative impact, while D alpha166, E alpha185, Hbeta112, Hbeta113 and E beta163 were less disruptive. Results are consistent with mutations interfering with class II interaction with another molecule which might or might not be another class II heterodimer. However, the larger negative impact of alpha chain mutations in salt bridge pairs suggests that these sites also help maintain some essential conformation of the alpha chain apart from any possible impact on dimer of dimers stability.     

Creating auxotrophic mutants in Methylophilus methylotrophus AS1 by combining electroporation and chemical mutagenesis

Examination of the superficial abdominal reflexes in patients thought to have idiopathic scoliosis has been considered possibly beneficial for deciding who should have magnetic resonance imaging to rule out syringomyelia. The purpose of this study was to determine what is normal for this examination. Thirty normal adolescents and 35 normal young adults underwent testing of the superficial abdominal reflexes and the patellar and Achilles deep tendon reflexes. Each test was repeated two times. Thirty-nine (60%) subjects had bilaterally equal abdominal reflexes. Nine (14%) subjects had asymmetric reflexes, and seven (11%) subjects had no reflex in at least one quadrant. No subjects had reflexes present on one side and absent on the other. Ten (15%) subjects had absence of the abdominal reflexes in all quadrants. Sixteen (25%) subjects had extinguishing of the reflex in at least one quadrant as the test was repeated. Eleven of these had asymmetric or partially absent reflexes initially. In contrast, the patellar and Achilles reflexes were more consistent. The patellar reflexes were bilaterally equal in 52 (85%), asymmetric in eight (13%), and absent in one (2%). The Achilles reflexes were bilaterally equal in 59 (97%), asymmetric in one (2%), and absent in one (2%). The finding of abdominal reflexes consistently present on one side and consistently absent on the other side did not occur in our normal subjects. This finding might warrant further workup if found in a patient with scoliosis. Other variations in abdominal reflex testing such as asymmetries, absent in some quadrants, and absent in all quadrants are fairly common in normal subjects.     

Solutions of a twelfth order thick plate theory

Summary A system of equilibrium equations governing a twelfth-order theory for the bending of thick plates is shown to be equivalent to a biharmonic equation together with four Helmholtz equations. These equations are closely related to equations derived by Cheng for an elasticity based thick plate theory. Detailed comparisons between the solutions for the displacements and stresses predicted by the approximate plate theory and an exact theory give some basis for deciding the applicability of the plate theory. As an example of the application of the solution procedure presented here, some earlier results for the decay parameters for the end problem for finite width plates are extended to the present case of twelfth-order plate theory.With 5 Figures     

Contents of alpha-fetoprotein in the blood of pregnant women as a criterion of the presence of congenital heart defects in the fetus

alpha-Fetoprotein (AFP) was measured in the blood of 16 women pregnant with twins at various terms of gestation and 24 pregnant women whose fetuses were found to have anencephaly, patent spina bifida, gastroschisis, renal polycystosis, or Down's disease. In Down's disease AFP level was 7 ng/ml (0.17 multiple of medians, MoM) at 17 weeks gestation and 6 ng/ml (0.12 MoM) at 19 weeks. In the fetal abnormalities studied AFP level was 372 ng/ml on average (6.8 MoM) at 16 to 18 weeks gestation, this being about 10 times higher than the normal level. AFP level in twin pregnancy at the same period was 2.3 MoM. AFP measurements are important for the prenatal diagnosis of fetal status in order to plan follow-up of pregnancy and labor management.     

Openers: Individuals who elicit intimate self-disclosure.

Presents an "Opener Scale" that measures the tendency to elicit intimate disclosure from others. Data from 740 undergraduates provided evidence for the scale's validity and reliability. In a face-to-face dyadic interaction between strangers in a laboratory study, 55 undergraduate women who scored either high or low on the Opener Scale were paired with other women who scored either high or low on a self-disclosure index. Low disclosers revealed more to high openers than to low openers. However, high disclosers were equally intimate with both types of partner. In a field study with 54 sorority women, acquaintances and friends were more willing to disclose to high openers than to low openers. High openers were more liked than low openers in the latter study only. It is suggested that high openers were able to elicit more disclosure because of their greater receptiveness and attentiveness and use of more follow-up questions. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radionuclide (MUGA) studies of left ventricular functional abnormalities in asymptomatic patients with sickle cell anemia

Radionuclide ventriculography was performed on 10 normal subjects and 39 patients with sickle cell anemia (10 homozygous and 29 heterozygous sicklers) at rest and after exercise. Their left ventricular (LV) function was assessed in both these situations. The results were then compared within the subgroups. The reduction in ejection fraction (EF) response (47.5 +/- 7 at rest and 46.4 +/- 8 at exercise in homozygous patients, and 52.4 +/- 8 at rest and 54.3 +/- 8 at exercise in heterozygous patients) was significant in both the homozygous and the heterozygous groups but more so in the former group. The diastolic filling was also significantly impaired in the homozygous group (PER 2.64 +/- 0.74, PFR 2.13 +/- 0.42 and PFR/HR 0.014 +/- 0.001). The study statistically demonstrates, that LV filling patterns are altered in the sickle cell patients, even in the absence of clinical symptoms relating to LV dysfunction. This fact may prove to be a marker of sickle cell heart disease. Frequent and significant sickling is probably the cause of more pronounced LV functional abnormalities in homozygous sicklers.