Hydroxyl radical-induced hydrogen/deuterium exchange in amino acid carbon-hydrogen bonds

BB rats are used as models of autoimmune human IDDM. Genetic control of IDDM in both species is complex, including both major histocompatibility complex (MHC)-linked and non-MHC-linked genes. DP-BB rats develop IDDM spontaneously. Expression of disease in these animals requires homozygosity at the lyp locus, which causes lymphopenia. All genetic analyses of BB rat diabetes to date have backcrossed to the DP-BB strain or used (DP-BB x non-BB)F2 animals to ensure that a fraction of progeny are homozygous for lyp. Here we report the analysis of a backcross of the DP-BB rat to the histocompatible WF rat. Neither WF nor (WF x DP-BB)F1 animals develop spontaneous IDDM. However, 95% of (WF x DP-BB)F1 rats and a fraction of (WF x DP-BB) x WF backcross animals readily develop IDDM after treatment with polyinosinic:polycytidylic acid and a cytotoxic anti-RT6.1 monoclonal antibody. Using simple sequence length polymorphism analysis, we have mapped loci on chromosomes 4 and 13 that show significant linkage to IDDM expression and insulitis. The susceptibility locus on chromosome 4 is linked to, but not identical to, lyp. We propose a disease model for the BB rat that requires 1) the RT1u MHC haplotype for disease susceptibility, 2) a new locus on chromosome 4 for disease initiation (as measured by insulitis), 3) a new locus on chromosome 13 for disease progression in response to environmental perturbation, and 4) lyp for spontaneous expression of disease.     

Heritability of anxiety sensitivity: a twin study

OBJECTIVE: In attempting to explain the familial predisposition to panic disorder, most studies have focused on the heritability of physiologic characteristics (e.g., CO2 sensitivity). A heretofore unexplored possibility is that a psychological characteristic that predisposes to panic-anxiety sensitivity-might be inherited. In this study, the authors examined the heritability of anxiety sensitivity through use of a twin group. METHOD: Scores on the Anxiety Sensitivity Index were examined in a group of 179 monozygotic and 158 dizygotic twin pairs. Biometrical model fitting was conducted through use of standard statistical methods. RESULTS: Broad heritability estimate of the Anxiety Sensitivity Index as a unifactorial construct was 45%. Additive genetic effects and unique environmental effects emerged as the primary influences on anxiety sensitivity. There was no evidence of genetic discontinuity between normal and extreme scores on the Anxiety Sensitivity Index. CONCLUSIONS: This study suggests that one psychological risk factor for the development of panic disorder-anxiety sensitivity-may have a heritable component. As such, anxiety sensitivity should be considered in future research on the heritability of panic disorder.     

Inhibition of hepatic inositol 1,4,5-trisphosphate receptor function by ethanol and other short chain alcohols

OBJECTIVE: To formulate the fundamental structure of caring as lived by Critical Care Nurses. DESIGN: Colaizzi's phenomenological research method and Diekelmann's dialogue technique were applied. SETTING: The home of each nurse constituted the setting for the interview. The nurses were employed in critical care units in six large metropolitan hospitals in the Southwest. SAMPLE: The availability sample consisted of 15 female critical care registered nurses. The nurses' mean age was 35 years. The mean number of years in critical care nursing was 4.7. One nurse was Asian, one was Hispanic, and 13 were Caucasian. RESULTS: Caring was composed of affective, cognitive, action, and outcome subprocesses. The caring process originated in the nurse's feelings and knowledge, and moved the nurse to competent actions that contributed to patient, family, and nurse outcomes. CONCLUSIONS: Understanding of the process of caring was strengthened by the findings. The decision process used by nurses would benefit from further examination for the presence of the affective and nurse outcome subprocesses.     

Apoptosis after traumatic human spinal cord injury

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.     

Tonsillar carcinoma: analysis of treatment results

A diffusion cell with an artificial membrane and the single-pass perfused rabbit ear were used to evaluate the percutaneous absorption of clonazepam from various 2-hydroxyethyl acetate (HEA) patches. The influence on drug permeation of the various type of enhancers (isopropylmyristate, lauryl alcohol, propylene glycol and water) in the patches was tested. A comparison between the two types of systems of percutaneous absorption of clonazepam has been done. The results showed that HEA patches produce controlled uniform drug release, modulated by the addition of enhancers.