Molecular motion and orientation distributions in melt-processed, fully aromatic liquid crystalline polyesters from 1H NMR

Fully-aromatic thermotropic liquid crystalline polymers (LCP) containing 4-hydroxybenzoic acid (HBA) and 6-hydroxy-2-naphthoic acid (HNA) were studied with 1H NMR. A two- or three-parameter nematic director distribution in molten or nearly molten samples was obtained via rigorous simulation of wideline spectral lineshapes. This methodology was further employed to yield the chain director distribution in macroscopic sections derived from a frozen contraction flow. In addition, the dynamic conformation of polymer chains through the melting transition was monitored via lineshape analysis of samples having (bulk) isotropic director distributions. Extension of rigorous 1H NMR spectral deconvolution to recently developed solid-state NMR imaging sequences is discussed.     

Application of a mechanistic model of bovine milk protein synthesis to examine the use of isotope labeling methods

Two types of models of bovine milk protein synthesis were used to simulate collection and analysis of data from infusion experiments involving isotope-labeled amino acids (AA). Analytical solutions to a system of ordinary differential equations that describe isotope enrichment curves of each AA pool within the mammary gland were derived and are presented. Numerical solutions from a dynamic mechanistic model suggest that normal experimental procedures can affect the shape of enrichment curves and, therefore, results derived from them. Simulation results suggest that standard methods utilizing in vivo isotope kinetics may be of limited value to characterize the metabolism of the bovine mammary gland, especially AA metabolism and milk protein synthesis and secretion. The results clearly demonstrate the flexibility of such models for the testing of many hypotheses and possible experimental protocols.     

Immunization of Aotus monkeys with recombinant Plasmodium falciparum hybrid proteins does not reproducibly result in protection from malaria infection

Plasmodium falciparum antigens SERP, HRPII, MSAI, and 41-3 have shown promise as vaccine components. This study aimed at reproducing and extending previous results using three hybrid molecules. Antibody responses were reproduced in Aotus monkeys, but solid protection from a P. falciparum blood-stage challenge that showed an unintendedly enhanced pathogenicity was not observed.     

A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12) particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer.     

Reported changes in sexual behavior in response to AIDS in the United States

BACKGROUND: The AIDS epidemic has profoundly affected public health policy and everyday choices of individuals. Understanding the self-protective strategies adopted by the general population is crucial to designing appropriate and more effective primary AIDS prevention strategies. METHODS: A probability sample of the U.S. adult population in 1992, the National Health and Social Life Survey (n = 3,159), addressed detailed aspects of sexual behavior. How respondents changed their sexual behavior due to AIDS was recorded verbatim and categorized for analysis. RESULTS: Twenty-nine percent of U.S. adults reported some sexual behavior change, primarily, reducing numbers of partners (12%), using condoms more frequently (9%), selecting partners more carefully (7%), changing attitude toward sex (4%), and abstinence (3%). Individuals most at risk show the greatest propensity to change although the actual risk-reduction strategies and the meanings assigned to those strategies vary considerably. Strategies are not all compatible with each other nor equally likely to be adopted by individuals with different lifestyles. CONCLUSIONS: Self-protective strategies to avoid AIDS are widespread, but primary prevention efforts should be targeted to particular circumstances and the self-protective propensities of each individual.