Aerobiology and inhalation exposure to biological select agents and toxins.

Aerosol is the most likely route of dissemination of biological select agents and toxins in a bioterrorist attack, regardless of the natural route of exposure to the agent. The use of animal models for testing preventative and therapeutic countermeasures requires knowledge of the pathogenesis of disease after inhalation exposure. Factors that relate to outcome after respiratory exposure include the inherent infectivity and virulence and/or toxicity of the agent in the host under investigation, in addition to characteristics of the aerosol particle and host that affect the delivered dose of, and host response to, the inhaled material. This introductory article discusses the emerging science of aerobiology and the unique features of respiratory tract anatomy, physiology, and immunology that are relevant to the pathogenesis of aerosolized biothreat agents.

Pain experiences of traumatically injured patients in a critical care setting.

BACKGROUND: Little is known about the acute pain experiences of traumatically injured critically ill patients. OBJECTIVES: To describe pain experiences of traumatically injured adults during the first 72 hours of hospitalization. METHODS: Thirty multiply injured adults at a level I trauma center participated in the study. Pain was measured by using the McGill Pain Questionnaire and a visual analog scale. Subjects completed pain measures while at rest in a supine recumbent position and after a turn onto the side. RESULTS: The typical subject was 37 years old, had 4 major blunt trauma injuries, and had received the equivalent of 55.9 mg of morphine during the 24 hours before data collection. Mean at-rest scores were 26.5 on the pain-rating index, 2 on the present pain intensity index, and 34.6 on the visual analog scale. Immediately after the turn, mean scores on the visual analog scale increased from 25 to 48.1 (P = .002). Other pain scores after the turn did not differ significantly from at-rest values. Subjects who turned had lower scores on the visual analog scale at rest (P = .02) and less anxiety (P = .02) than did those who refused to turn. Ninety-six percent reported pain in the injured areas, and 36% reported pain related to biomedical devices. No relationship was found among reported pain and demographic, treatment, or clinical variables. CONCLUSIONS: Additional research is needed on pain at rest and during commonly performed procedures and on improved methods for pain relief in traumatically injured critically ill patients.

Signal transducer and activator of transcription 3 activates CCAAT enhancer-binding protein delta gene transcription in G0 growth-arrested mouse mammary epithelial cells and in involuting mouse mammary gland.

The CCAAT enhancer-binding protein (C/EBP) family of transcription factors is implicated in the regulation of cell proliferation and differentiation in a variety of tissues. C/EBPdelta is involved in regulating G(0) growth arrest and apoptosis of mouse mammary epithelial cells. This study shows that activation of signal transducer and activator of transcription 3 (Stat3), but not activation of Stat1 or Stat5, occurs concurrently with G(0) growth arrest of HC11 mouse mammary epithelial cells, but not NIH 3T3 fibroblasts. Promoter analysis demonstrates that the C/EBPdelta promoter fragment involved in transcriptional activation during G(0) growth arrest contains a Stat3 binding site and that mutation of this site eliminates the G(0) growth arrest inducibility of the C/EBPdelta promoter. Overexpression of Stat3 increases C/EBPdelta promoter activity during G(0) growth arrest of HC11 cells, whereas dominant negative Stat3 decreases C/EBPdelta promoter activity under the same conditions. Neither Stat3 overexpression nor dominant negative Stat3 expression influences C/EBPdelta promoter activity in growing HC11 cells or G(0) growth-arrested NIH3T3 cells, demonstrating that the effect is specific to G(0) growth arrest of mammary epithelial cells. Band shift assays and antibody interference assays demonstrate specific binding of Stat3 to the acute phase response element in the C/EBPdelta promoter in G(0) growth-arrested HC11 cell extracts and 24 h involuting mouse mammary gland extracts. These data indicate that Stat3 activates C/EBPdelta transcription in G(0) growth-arrested mouse mammary epithelial cells and binds to the C/EBPdelta promoter during involution. An autocrine mechanism of Stat3 activation is proposed.

Transcriptional regulation of C/EBPdelta in G(0) growth-arrested mouse mammary epithelial cells.

Little is known about the control of cell cycle exit/G(0) entry, or the regulation of genes that are expressed during G(0). In this report we used primer extension analysis to demonstrate the high level of C/EBPdelta mRNA expression in G(0) growth-arrested HC11 mouse mammary epithelial cells and to identify the C/EBPdelta transcription start site. The C/EBPdelta gene transcription rate and promoter activity are both highly induced in G(0) growth-arrested HC11 cells. The C/EBPdelta gene promoter also exhibits G(0)-specific autoregulation. In contrast, the C/EBPdelta promoter activity decreases in G(0) growth-arrested NIH 3T3 cells. These data indicate that C/EBPdelta is among a relatively small number of genes actively transcribed during G(0) growth arrest. C/EBPdelta may regulate the expression of genes implicated in the initiation or maintenance of mammary epithelial cell G(0) growth arrest.

CCAAT/enhancer-binding protein delta regulates mammary epithelial cell G0 growth arrest and apoptosis.

CCAAT/enhancer-binding proteins (C/EBPs) are a highly conserved family of DNA-binding proteins that regulate cell-specific growth, differentiation, and apoptosis. Here, we show that induction of C/EBPdelta gene expression during G0 growth arrest is a general property of mammary-derived cell lines. C/EBPdelta is not induced during G0 growth arrest in 3T3 or IEC18 cells. C/EBPdelta induction is G0-specific in mouse mammary epithelial cells; C/EBPdelta gene expression is not induced by growth arrest in the G1, S, or G2 phase of the cell cycle. C/EBPdelta antisense-expressing cells (AS1 cells) maintain elevated cyclin D1 and phosphorylated retinoblastoma protein levels and exhibit delayed G0 growth arrest and apoptosis in response to serum and growth factor withdrawal. Conversely, C/EBPdelta-overexpressing cells exhibited a rapid decline in cyclin D1 and phosphorylated retinoblastoma protein levels, a rapid increase in the cyclin-dependent kinase inhibitor p27, and accelerated G0 growth arrest and apoptosis in response to serum and growth factor withdrawal. When C/EBPdelta levels were rescued in AS1 cells by transfection with a C/EBPdelta "sense" construct, normal G0 growth arrest and apoptosis were restored. These results demonstrate that C/EBPdelta plays a key role in the regulation of G0 growth arrest and apoptosis in mammary epithelial cells.

Thoracic and abdominal blastomycosis in a horse.

A 5-year-old Quarter Horse mare was examined because of lethargy, fever, and weight loss of 1 month's duration. Thoracic auscultation revealed decreased lung sounds cranioventrally. Thoracic ultrasonography revealed bilateral anechoic areas with hyperechoic strands, consistent with pleural effusion and fibrin tags. A large amount of free fluid was evident during abdominal ultrasonography. Abnormalities included anemia, hyperproteinemia, hyperglobulinemia, hyperfibrinogenemia, and hypoalbuminemia. Thoracic radiography revealed alveolar infiltrates in the cranial and caudoventral lung fields. A cavitary mass, consistent with an abscess, could be seen caudodorsal to the crura of the diaphragm. Ultrasonographic evaluation of this area revealed a hypoechoic mass with septations. Bilateral thoracocentesis was performed. Bacterial culture of the pleural fluid did not yield growth, but Blastomyces dermatitidis was isolated from pleural fluid, abdominal fluid, and an aspirate of the abscess. The mare was euthanatized, and a diagnosis of thoracic and abdominal blastomycosis was confirmed at necropsy.

Strategies for pain management in traumatic thoracic injuries.

Tissue damage, such as that caused by traumatic injury, is associated with the sensations and responses characterized initially as acute pain. It is known that unrelieved pain contributes to morbidity and mortality in surgical patients. Is pain contributing to morbidity and mortality in critically injured patients as well? Nurses are in a critical position to assess and manage pain. They must be familiar with the wide variety of available pain management techniques and be prepared to advocate their use.

Resonance Raman spectroscopic studies of adriamycin and copper(II)-adriamycin and copper(II)-adriamycin-DNA complexes.

Characteristic resonance Raman spectra are observed on ionization of the phenolic groups in adriamycin. On the basis of these results, vibrational assignments for the Raman bands of adriamycin are reported. Distinct Raman spectra are observed for Cu(II)-adriamycin complexes at pH approximately 5 and pH approximately 13. The data indicate that at lower pH a bis complex of Cu(II) is formed, which transforms to a polymeric Cu(II) chelate at higher pH. Upon interaction of the metal-drug complex with calf thymus DNA at pH approximately 5, a ternary complex is formed in which the Cu(II)-complexed adriamycin is intercalated into DNA.