The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.

The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.     

Estimation of average flow in ungated 3D phase contrast angiograms

Three dimensional (3D) phase contrast angiograms contain velocity data, which is discarded after the reconstruction of the projections. In extension to earlier work on velocity quantification with ungated 2D phase data, this paper shows that a useful estimate of the average velocity and flow rate can be extracted from ungated 3D phase contrast angiograms. Simulations and experiments in a phantom and in vivo were performed. For pulsatile flow and strong spin saturation, an over-estimation of the flow rate at the net in-flow end of the imaging volume and underestimation at the net out-flow end was observed. Imaging at lower RF tip angles yielded flow rates close to the correct value within the entire imaging volume. In contrast to ungated 2D experiments, the flow rates determined by repeated 3D experiments showed no variation.     

Oblique muscle palsies fixating with the paretic eye

Palsy of the superior oblique muscle is one of the most commonly occurring entities in strabismus; the clinical characteristics are easily recognizable. Isolated inferior oblique muscle palsy, although anatomically enigmatical, is also known to ophthalmologists. When a patient with an oblique muscle palsy chooses to fixate with the paretic eye, characteristic patterns of motility may be obscured. Patients with superior oblique muscle palsy or isolated inferior oblique muscle palsy who habitually fixate with the paretic eye, may present with limited elevation or depression respectively. In each case, limited motility exists secondary to decreased innervational input to the contralateral antagonist of the paretic muscle, or to a mechanical restriction caused by prolonged contracture of the yoke of the paretic muscle. Inhibitional palsy of the contralateral antagonists and the fallen and rising eye syndromes may present diagnostic dilemmas unless the underlying oblique muscle palsy is recognized. Proper diagnosis may be obtained with three clinical tests; the 3-step test, the comparison of ductions to versions, and forced ductions.     

Expression of a methotrexate-resistant dihydrofolate reductase gene by transformed hematopoietic cells of mice

DNA-mediated gene transfer was used to introduce DNA from a methotrexate-resistant mouse fibroblast cell line into mouse bone marrow cells. This cell line contained a methotrexate-resistant dihydrofolate reductase, active at 10^?4 M methotrexate, which was electrophoretically separable from the wild-type mouse enzyme. Transformed hematopoietic cells were returned to irradiated mice and selected in vivo by methotrexate administration. Some recipients of transformed marrow cells expressed the electrophoretically distinct, methotrexate-resistant dihydrofolate reductase in hematopoietic cells. These observations suggest that successful transformation of marrow stem cells to methotrexate resistance is accomplished by insertion of a dihydrofolate reductase gene coding for a mutant enzyme that is highly resistant to methotrexate.     

Expression of Epidermal Growth Factor Receptors in Human Breast Cancer: Mass Versus Ligand Binding Capacity

Abstract: Thirty percent of lymph node-negative women with primary breast cancers are at high risk for early recurrence of metastatic disease and diminished survival. Identification of these high-risk patients is a long-term objective of our laboatory, and the epidermal growth factor receptor (EGFR) was investigated as a prognostic factor, EGFR was measured by a ligand binding assay developed in house, in the competition mode that served as the "gold standard" for assessing receptor content and activity. In contrast, measurements of mass (content) were performed by an enzyme immunoassay (EIA) from Ciba Corning Diagnostics (Alameda, CA) and by an enzyme-linked immunosorbent assay (ELISA) from Oncogene Science (Uniondale, NY). A total of 78 breast carcinomas were examined. The median binding capacity measured with [¹²⁵I]EGF was 13 fmol/mg membrane protein (range 0–981), that measured by EIA was 8 fmol/mg (range 1–125), while EGFR measured by ELISA was 135 (range 0–751). Distribution of EGFR did not appear to vary as a function of patient age. Neither the results from EIA nor those from ELISA correlated with those obtained by the ligand binding assay. However, there was a good correlation of results obtained by the two antibody-based assays despite the fact that the calibration of standards was considerably different. These data suggest that EGFR should be measured by ligand binding assay for clinical studies; mass assays based on antibody reagents will require further development.     

Chronic application of NMDA decreases the NMDA sensitivity of the evoked tectal potential in the frog.

The activity-dependent mechanism that refines the topography of the retinotectal projection in frogs is mediated by the NMDA receptor. Earlier studies found that chronic treatment of the optic tectum with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (DL-AP5) desegregated eye-specific stripes in three-eyed frogs, while chronic treatment with NMDA sharpened stripe borders (Cline et al., 1987; Cline and Constantine-Paton, 1990). We now report that this same chronic treatment with NMDA decreases the electro-physiologically measured sensitivity of the optic tectum to applied NMDA: acute application of a given concentration of NMDA decreased the evoked tectal potential to a lesser extent in animals chronically treated with NMDA than it did in normal and sham-treated animals. This is observed as a shift to the right in the NMDA dose-response curves for both the positive and negative postsynaptic components of the evoked tectal response. We believe that this decreased NMDA receptor effectiveness further restricts the intermingling of axon branches from the two eyes by limiting synapse stabilization to areas where afferent activity is most correlated. This would account for the anatomical sharpening of stripe borders (i.e., increased afferent segregation). Quantitative autoradiographic analysis of 3H-glutamate binding to NMDA receptors indicated that binding densities within the tectum did not differ between control groups and NMDA chronically treated groups. We suggest that in the experimental animals the response to NMDA may be decreased by a change in the effectiveness of individual NMDA receptors rather than by decreases in receptor number. This experimentally induced change may be analogous to naturally occurring decreases in receptor function that correlate with the end of some periods of visual plasticity in mammals.     

Physical attractiveness and the personality resemblance of identical twins

The physical attractiveness of 25 pairs of monozygotic (MZ) twins was rated independently for twins A and B. The MZ twins were rated alike in their physical attractiveness (r=0.54; corrected for attenuation,r=0.94). Physical attractiveness was uncorrelated with verbal intelligence but was associated, controlling statistically for the sex difference in attractiveness favoring females, with three of the eight traits in the Comrey inventory: Conformity, Extraversion, and Emotional Stability. In both sexes, greater emotional stability was associated with attractiveness; in males greater extraversion; and in females, greater conformity. When these twin correlations were adjusted for this association with attractiveness, the mean change in the value ofr was only 0.03, indicating that physical attractiveness does not appear to bias conclusions from twin studies.