Inhibition of immunologic injury of cultured cells infected with lymphocytic choriomeningitis virus: role of defective interfering virus in regulating viral antigenic expression

The expression of viral antigens on the surfaces of lymphocytic choriomeningitis virus (LCMV)-infected L-929 cells peaked 2-4 days postinfection and thereafter precipitously declined. Little or no viral antigen was expressed on the plasma membrane surfaces of persistently infected cells, but LCMV antigens were clearly present in the cytoplasms of most of those cells. Cells early after acute infection (days 2-4) were lysed by both virus-specific antibody and complement (C) and immune T lymphocytes. To the contrary, antibody and C did not kill persistently infected cells, but T lymphocytes did kill such cells although at a lower efficiency than acutely infected cells. The expression of viral antigens on the surfaces of infected cells was regulated by the virus- cell interaction in the absence of immune reagents and was closely associated with defective interfering (DI) LCMV interference. DI LCMV, per se, blocked the synthesis and cell surface expression of LCMV antigens, and DI LCMV generation immediately preceded a precipitous reduction in cell surface antigenicity during the acute infection. Persistently infected cells produced DI LCMV but no detectable S LCMV. Peritoneal cells isolated from mice persistently infected with LCMV resembled cultured persistently infected cells in their reduced expression of cell surface antigens and their resistance to LCMV superinfection. It is proposed that DI virus-mediated interference with viral protein synthesis may allow cells to escape immune surveillance during persistent infections.     

Drugs and probes: the symbiotic relationship between pharmaceutical discovery and imaging science.

Pharmaceutical research and imaging science are becoming increasingly intertwined. Positron emission tomography (PET) is a molecular imaging technique with particularly broad application in drug discovery and development. At the same time, modern techniques of drug discovery are helping accelerate the development of new PET probes. This article describes the relationship between the two fields, with particular consideration of practical and strategic limitations to full utilization of available technology.     

Acute changes in systemic blood pressure and urine output of conscious rats following exchange transfusion with diaspirin-crosslinked hemoglobin solution

This report describes acute changes in systemic blood pressure and urine output observed after a 50-percent isovolemic exchange transfusion (ET) with diaspirin-crosslinked hemoglobin (alpha alpha Hb). Stroma-free Hb was crosslinked between the alpha chains by using a 14C-labeled diaspirin, bis(3,5-dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with 14C-labeled alpha alpha Hb solution (8.0 g/dL [80 g/L]). This resulted in systemic hypertension for 3 to 4 hours after ET (mean arterial pressure rose from 120 to 145 torr at 1 to 2 hours after ET) and mild bradycardia for 2 to 3 hours (heart rate decreased from 420 to 335 beats/min [bpm] before stabilizing at 360 +/− 10 bpm). This was accompanied by significant diuresis immediately after ET (5- 6-fold increase in urine output, which normalized after 12 hours), and mild hemoglobinuria. The total amount of Hb recovered in the urine was < 5 percent of the injected dose. Reversed-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the presence of crosslinked alpha alpha Hb molecules in the urine. Renal excretion of radioactivity was significantly greater, with 20 percent of total radioactivity being eliminated within 24 hours. The plasma half-life for alpha alpha Hb was 5 hours (administered dose, 2.4 g Hb/kg body weight). Thus, infusion of alpha alpha Hb caused a transient systemic hypertension, and intramolecular crosslinking alone was not enough to exclude completely the filtration of alpha alpha Hb by the kidneys.     

Selective in vivo removal of rheumatoid factor by an extracorporeal treatment device in rheumatoid arthritis patients

A prospective phase II trial was conducted to assess the feasibility, tolerance, and efficacy of a device designed for selective removal of rheumatoid factor from the plasma of rheumatoid arthritis patients. The device contained terpolymer hydrogel-coated plates with chemically attached, aggregated human immunoglobulin G, and it operated as an immunoaffinity column. Sixty-one patients aged 25 to 73 underwent weekly plasmapheresis treatments (the primary therapy phase). During the trial, patients continued current rheumatoid arthritis medications without dose adjustments. All patients received two to six treatments (primary therapy). Responding patients were eligible to continue apheresis treatment every 2 to 6 weeks (maintenance therapy). No serious, untoward side effects were noted in the course of this study; of 640 treatments, only 2 (in different patients) were aborted, one because of complaints of dizziness and angioedema and the other because of chest tightness and shortness of breath. Except for a significant (p less than 0.05) decrease in serum iron, no significant changes in complete blood count, serum electrolytes, renal and hepatic function tests, or serum C3 and C4 were noted. Although the trial was not designed to determine clinical efficacy, patients noted less morning stiffness, longer time to onset of fatigue, and improved global pain assessment (p less than 0.004); significant objective improvements were noted in joint pain, tenderness, swelling, and the number of affected joints (p less than 0.001). One-half of the treated patients had at least a 50 percent improvement in objective measures of antirheumatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Story as a reflective process for nurses

This paper uses two practice stories (included as appendices) to illustrate the significance and value of story as a reflective technique for nurses. It employs an explicit framework to draw out the importance of story-telling and suggests that stories can help nurses expose the therapeutic dimension of their work. This aspect is conceived in terms of the concept of 'therapeutic nursing'. We will draw upon the practice stories of one of the authors (Strathie), and it is that author's experience of story-telling to which reference is made. Readers are urged to read the practice stories so that they can appreciate the points made in the text of the paper.     

Residential care placement: perceptions among elderly Chinese people in Hong Kong

A qualitative study was designed to explore the perceptions of residential care placement among elderly Chinese people in Hong Kong. Content analysis of the semi-structured interviews with 20 community residents aged 60 years or over revealed that elderly people in Hong Kong generally had mixed feelings towards such placement. While they believed that residential care was an unavoidable alternative to family care in their later lives it was an important source of fear in their later years, especially for those who perceived their health as deteriorating. Residential care homes were generally seen as the ultimate 'dumping place' where one would 'idle till death' and the quality of care provided in these homes was anticipated to be problematic. It was found that most of these beliefs were formed as a result of indirect experience through 'listening to stories of neglect or abuse from friends and relatives whose relatives were residential care home residents'. Implications for professionals working with elderly people are discussed in the light of these findings.     

Inhibitory effect of 0 degree C storage on the proliferation of Yersinia enterocolitica in donated blood

BACKGROUND: Yersinia enterocolitica is frequently identified in cases of bacterial sepsis due to red cell transfusion. One of the features that makes Y. enterocolitica particularly dangerous is that, unlike most other bacterial contaminants of blood components, this organism can actively multiply in currently recommended refrigerator temperatures (1-6 degrees C). The effect of a colder than normal storage temperature on Y. enterocolitica growth was investigated to determine whether bacteria growth could be reduced or inhibited at 0 degree C. STUDY DESIGN AND METHODS: Twenty-four units of freshly collected donated blood were obtained. Three sets of 7 units each were inoculated with Y. enterocolitica O:3, Y. enterocolitica O:20, and Y. enterocolitica O:5, 27, respectively. The remaining 3 units served as uninoculated controls. Each of the 24 bags was split into two equal aliquots, with one aliquot stored at 4 degrees C and the other at 0 degree C. Bacteria growth was measured twice weekly for 6 weeks. Endotoxin and hemoglobin levels were also measured at selected intervals. RESULTS: Bacteria growth was detected earlier and in higher concentrations in the aliquots stored at 4 degrees C. Twenty-two of the 42 inoculated aliquots had measureable bacteria growth. Thirteen aliquots had been maintained at 4 degrees C, and nine had been stored at 0 degree C. Sixteen of these 22 aliquots were matched pairs. Exponential growth was detected after 14 to 32 days in the 4 degrees C aliquots and after 28 to 39 days in the 0 degree C aliquots. Final bacteria counts were much higher in the 4 degrees C aliquots (10(5)- 10(14) colony-forming units/mL) than in the 0 degree C aliquots (10(1)- 10(4) colony-forming units/mL) on Day 42. Endotoxin was present in all 13 of the 4 degrees C aliquots with actively growing Y. enterocolitica. CONCLUSION: Storage of red cells at 0 degree C markedly prolongs the time required for Y. enterocolitica to achieve exponential grwoth and results in lower concentrations of bacteria.