Subunit peptide cancer vaccines targeting activating mutations of the p21 ras proto-oncogene

BACKGROUND AND OBJECTIVES: Physicians in the 1920s and 1930s began to treat patients with chronic pain syndromes using regional anesthetic techniques for both temporary and permanent block of pain pathways. The founding of the American Society of Regional Anesthesia (ASRA) in 1923 provided a unique venue for the dissemination of information concerning regional anesthesia for both surgery and chronic pain management. METHODS: The growth of chronic pain management on a national basis was assessed by using the Quarterly Cumulative Index to the Medical Literature to trace the distribution of information on regional anesthesia. From the Minutes of Meeting of the American Society of Regional Anesthesia, presented papers and the discussion that followed were analyzed. RESULTS: Inquiries into regional anesthesia during the 1920s and 1930s predominantly dealt with technique. For the first time pain papers were listed under the regional anesthesia heading in the Index. The papers presented at ASRA meetings during the period helped develop the use of regional anesthesia for both chronic pain management and surgical anesthesia. CONCLUSIONS: The ASRA was instrumental in bringing together physicians interested in regional anesthesia and pain management. During the 1930s physician anesthetists came to predominate as the organization's officers and members and helped translate the work of the ASRA into a part of the knowledge required to be a specialist physician in anesthesia.     

The energy cost of walking before and after significant weight loss

The purpose of this study was to determine whether significant weight loss reduced the energy cost of activity more than that expected based on decreased body weight. Standing energy expenditure was measured and subtracted from the total energy cost of walking to determine ambulatory energy expenditure (AEE). The energy cost of walking was determined in 11 obese women at baseline, week 9 [after 8 wk of a 1758-3349 kJ.d-1 diet], and week 22 (after 2 wk of weight stability). AEE accounted for 80% of the energy cost of walking. Body weight was the principal determinant of AEE, but the relationship was not 1:1. Subjects reduced body weight by 13% at week 9 and 21% at week 22. Analyses which controlled for the relationship between AEE and weight at baseline, showed no change in AEE at week 9. By contrast, at week 22, AEE was reduced more than expected based on a lower body weight. These findings suggest that after significant weight loss, reduced-obese persons will expend less energy for the same activity, even after accounting for the decrease in body weight. These data also suggest that weight-based estimates of exercise energy expenditure may be inappropriate after significant weight loss.     

The proximal ligand variant His93Tyr of horse heart myoglobin

The spectroscopic and structural properties of the His93Tyr variant of horse heart myoglobin have been studied to assess the effects of replacing the proximal His residue of this protein with a tyrosyl residue as occurs in catalases from various sources. The variant in the ferric form exhibits electronic spectra that are independent of pH between pH 7 and 10, and it exhibits changes in absorption maxima and intensity that are consistent with a five-coordinate heme iron center at the active site. The EPR spectrum of the variant is that of a high-spin, rhombic system similar to that reported for bovine liver catalase. The 1D 1H-NMR spectrum of the variant confirms the five-coordinate nature of the heme iron center and exhibits a broad resonance at 112.5 ppm that is attributable to the meta protons of the phenolate ligand. This result indicates that the new Tyr ligand flips at a significant rate in this protein. The thermal stability of the Fe(III) derivative is unchanged from that of the wild-type protein (pH 8) while the midpoint reduction potential [-208 mV vs SHE (pH 8.0, 25 degrees C)] is about 250 mV lower. The three-dimensional structure of the variant determined by X-ray diffraction analysis confirms the five-coordinate nature of the heme iron center and establishes that the introduction of a proximal Tyr ligand is accommodated by a shift of the F helix (residues 88-99) in which this residue resides away from the heme pocket. Additional effects of this change are small shifts in the positions of Leu29, a heme propionate, and a heme vinyl group that are accompanied by altered hydrogen bonding interactions with the heme prosthetic group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tolerance space and molecular similarity

Molecular similarity methods were used in selecting K nearest neighbors and in estimating mutagenicity of 95 aromatic amines and boiling points of a large set of over 2,900 compounds. Similarity is analyzed in terms of the concept of tolerance space. Specifically, the role of non-transitivity of the tolerance relation in estimating properties using similarity methods is examined.