Structure-based design of a lysozyme with altered catalytic activity

Here we show that the substitution Thr 26-->His in the active site of T4 lysozyme causes the product to change from the alpha- to the beta-anomer. This implies an alteration in the catalytic mechanism of the enzyme. From the change in product, together with inspection of relevant crystal structures, it is inferred that wild-type T4 lysozyme is an anomer-inverting enzyme with a single displacement mechanism in which water attacks from the alpha-side of the substrate. In contrast, the mutant T26H is an anomer-retaining enzyme with an apparently double displacement mechanism in which a water molecule attacks from the opposite side of the substrate. The results also show that the mechanism of wild-type T4 lysozyme differs from that of hen egg-white lysozyme even though both enzymes are presumed to have evolved from a common precursor.     

N-methyl-D-aspartate-stimulated increases in intracellular calcium exhibit brain regional differences in sensitivity to inhibition by ethanol

To determine what effect ovariectomy and the accompanying sudden loss of circulating gonadal hormones has on spatial learning performance in the adult rat, two groups of rats were tested on the Lashley III simple alley maze following surgery. Ovariectomized animals were compared with a control group of animals that underwent laparotomy at the same time. The ovariectomized group evidenced superior performance on the maze task, as measured by latency to reach goal (running times) and error scores. It is suggested that this finding provides further evidence for the role of gonadal steroid hormones in the manipulation of functions related to learning and memory, especially in the hippocampus.     

Penetrating trauma of the internal carotid artery

OBJECTIVE: To assess management of penetrating internal carotid artery (ICA) injuries. DESIGN: Retrospective review of institutional protocol. SETTING: Level 1 trauma center in a major urban area. PATIENTS: Sixty-one patients with penetrating ICA injuries. INTERVENTIONS: In the period 1975 to 1987 (group 1; n = 36), management was based on individual surgeons' preferences. Between 1988 and 1995 (group 2; n = 25), an algorithm was employed: (1) hemodynamically stable patients with suspected ICA injuries underwent a diagnostic angiography; (2) surgically accessible injuries were reconstructed regardless of neurologic status with 2 exceptions: (a) neurologically intact patients with ICA occlusion were treated by anticoagulation and mild pharmacological hypertension and (b) minimal nonocclusive injuries were managed nonoperatively and followed up by serial angiography or duplex ultrasonography; and (3) heparinization, shunting, and completion angiography were employed. MAIN OUTCOME MEASURES: Neurologic status at admission and discharge were compared by the Fisher exact test. RESULTS: In group 1, 24 patients (67%) presented neurologically intact, and 12 (33%) with a deficit. Sixteen injuries were managed nonoperatively, 14 were repaired, and 6 were ligated. At discharge 6 (17%) were improved, 24 (66%) were unchanged, 6 (17%) were worse. Four patients (11%) died of cerebrovascular causes. In group 2, 19 patients (76%) presented neurologically intact, and 6 (24%) with a deficit. Eleven injuries were managed nonoperatively, 12 were repaired, and 2 were ligated. A death occurred in a patient who arrested, was admitted to the hospital in a coma, and died before ICA repair. CONCLUSIONS: Neurologic outcome after ICA injury is enhanced by an algorithm predicated on the liberal use of angiography, a predefined surgical approach, and selective observation.     

Manifestations of dynamic strain aging in soft-oriented NiAl single crystals

The tensile and compressive properties of six NiAl-base single-crystal alloys have been investigated at temperatures between 77 and 1200 K. The normalized critical resolved shear stresses (CRSS/E) and work-hardening rates (θ/E) for these alloys generally decreased with increasing temperature. However, anomalous peaks or plateaus for these properties were observed in conventional purity (CPNiAl), Si-doped (NiAl-Si), C-doped low Si (UF-NiAll), and Mo-doped (NiAl-Mo) alloys at intermediate temperatures (600 to 1000 K). This anomalous behavior was not observed in high-purity, low interstitial material (HP-NiAl). Low or negative strain-rate sensitivities (SRS) also were observed in all six alloys in this intermediate temperature range. Coincident with the occurrence of negative strain-rate sensitivities was the observation of serrated stress-strain curves in the CPNiAl and NiAl-Si alloys. These phenomena have been attributed to dynamic strain aging (DSA). Chemical analysis of the alloys used in this study suggests that the main specie responsible for strain aging in NiAl is C but indicate that residual Si impurities can enhance the strain aging effects. The corresponding dislocation microstructures at low temperatures (300 to 600 K) were composed of welldefined cells. At intermediate temperatures (600 to 900 K), either poorly defined cells or coarse bands of localized slip, reminiscent of the vein structures observed in low-cycle fatigue specimens deformed in the DSA regime, were observed in conventional purity, Si-doped, and in Mo-doped alloys. In contrast, a well-defined cell structure persisted in the low interstitial, high-purity alloy. At elevated temperatures (≥1000 K), more uniformly distributed dislocations and sub-boundaries were observed in all alloys. These observations are consistent with the occurrence of DSA in NiAl single-crystal alloys at intermediate temperatures.