Acquired hypogammaglobulinemia and pathogen-specific antibody depletion after solid organ transplantation in human immunodeficiency virus infection: A brief report.

Hypogammaglobulinemia (HGG) frequently occurs in recipients after types of (SOT). The incidence and significance of HGG in HIV+ recipients of SOT are just being explored. We reported that 12% of the recipients in the SOT in multi-center HIV-TR (HIV-TR) Study developed moderate or severe HGG at 1 year. In LT recipients, this was associated with serious infections and death. We have now further characterized the decreased antibodies in HIV+ SOT recipients who developed HGG. We measured the levels of pathogen-specific antibodies and poly-specific self-reactive antibodies (PSA) in relation to total IgG levels from serial serum samples for 20 HIV+ SOT recipients who developed moderate to severe HGG following SOT. Serum antibody levels to measles, tetanus toxoid, and HIV-1 were determined by EIA. Levels of PSAs were determined by incubating control lymphocytes with patient serum, staining with anti-human IgG Fab-FITC, and analysis by flow cytometry. Levels of PSA were higher compared to healthy, HIV-uninfected controls at pre-transplant baseline and increased by weeks 12 and 26, but the changes were not significant. Likewise, anti-HIV antibody levels remained unchanged over time. In contrast, antibody levels against measles and tetanus were significantly reduced from baseline by week 12, and did not return to baseline, even after 2 years. For HIV patients who develop moderate to severe HGG after transplant, the reduction in IgG levels is associated with a significant decrease in pathogen-specific antibody titers, while PSA levels and anti-HIV antibodies are unchanged. This may contribute to infectious complications and other clinical endpoints.

Testing an electrostatic interaction hypothesis of hepatitis B virus capsid stability by using an in vitro capsid disassembly/reassembly system.

To test a previously coined "charge balance hypothesis" of human hepatitis B virus (HBV) capsid stability, we established an in vitro disassembly and reassembly system using bacterially expressed HBV capsids. Capsid disassembly can be induced by micrococcal nuclease digestion of encapsidated RNA. HBV core protein (HBc) mutants containing various amounts of arginine were constructed by serial truncations at the C terminus. Capsids containing smaller amounts of arginine (HBc 149, 154, and 157) remained intact after micrococcal nuclease digestion by native gel electrophoresis. Capsids containing larger amounts of arginine (HBc 159, 164, 169, and 171) exhibited reduced and more diffuse banding intensity and slightly upshifted mobility (HBc 159 and 164). Capsids containing the largest amounts of arginine (HBc 173, 175, and 183), as well as HBc 167, exhibited no detectable banding signal, indicating loss of capsid integrity or stability. Interestingly, capsid reassembly can be induced by polyanions, including oligonucleotides, poly-glutamic acid, and nonbiological polymer (polyacrylic acid). In contrast, polycations (polylysine and polyethylenimine) and low-molecular-weight anions (inositol triphosphate) induced no capsid reassembly. Results obtained by gel assay were confirmed by electron microscopy. Reassembled capsids comigrated with undigested parental capsids on agarose gels and cosedimented with undigested capsids by sucrose gradient ultracentrifugation. Taken together, the results indicate that HBV capsid assembly and integrity depend on polyanions, which probably can help minimize intersubunit charge repulsion caused mainly by arginine-rich domain III or IV in close contact. The exact structure of polyanions is not important for in vitro capsid reassembly. A large amount of independent experimental evidence for this newly coined "electrostatic interaction hypothesis" is discussed.

Health as expanding consciousness with families with a child with special healthcare needs.

Families have health experiences that become enfolded within their life patterns. Based within Newman's conceptualization of health as expanding consciousness, the purpose of this study was to develop knowledge about the nurse-client process of facilitating health in families who have a child with special healthcare needs. The research as praxis method was used to answer the research question, What is the evolving pattern of the nurse-client process that facilitates health as expanding consciousness in families who have a child with special healthcare needs?

Light augments tooth whitening with peroxide.

BACKGROUND: The authors tested the adjunctive use of light with a 15 percent peroxide gel as a single-visit, in-office tooth whitening system. METHODS: Subject (N = 87) with stained (> shade D4, Vita Zahnfabrik, Bad Säckingen, Germany) anterior teeth were randomly assigned to test (peroxide and light), peroxide control (peroxide gel) or light control (placebo gel and light) groups and were treated for one hour. The researchers evaluated tooth shade, color and subject response at baseline and posttreatment and at three and six months posttreatment. RESULTS: The initial shade unit reduction of combined light and peroxide treatment (8.4) was greatest compared with that of peroxide alone (5.9) and of light alone (4.9). Approximately 88 percent of these effects persisted for six months. Lightness was increased and yellowness decreased to a significantly greater extent in the test group than in either control. These findings were corroborated by subject evaluation. One week after treatment, moderate to greatly increased tooth sensitivity occurred in 20 percent of test subjects, 21.7 percent of peroxide control subjects and none of the light control subjects. Neither tooth sensitivity nor gingival redness was present at the three- and six-month visits. CONCLUSIONS: Peroxide and light treatment significantly lightened the color of teeth to a greater extent than did peroxide or light alone, with a low and transient incidence of tooth sensitivity. CLINICAL IMPLICATIONS: Light can increase the tooth-whitening effect of peroxide, thereby increasing the effectiveness of tooth-whitening procedures.

A world of no boundaries.

Ken Wilber's philosophy of no boundaries provides a backdrop for letting go of boundaries between art and science, research and practice, and nursing theories. Major nursing concepts are cited from a variety of theoretical persuasions to illustrate a statement of a unified perspective of the discipline. The author calls for exploration of a world of no boundaries in the expansion of nursing knowledge and practice.

The pattern that connects.

Debate over whether nursing is an art or a science culminates in the need for integration of the two as a guide to practice. The historical development of nursing knowledge reveals a spectrum of evolution from physical care to interpersonal relationships to an integrative approach and, most recently, to a unitary perspective. The author proposes pattern as the integrating factor that eliminates the dichotomies of traditional art and science and transforms nursing knowledge to a higher dimension that includes and transcends the knowledge that has gone before. Nursing praxis is presented as integrated theory-research-practice that is consistent with a unitary perspective.

Microbial colonization of electrocardiographic telemetry systems before and after cleaning.

BACKGROUND: Nosocomial infections caused by multidrug-resistant organisms are commonly associated with longer hospital stays up to 12 to 18 days and annual estimated costs of $5.7 billion to $6.8 billion. One common mode of transmission is cross-contamination between patients and providers via surface contaminants on devices such as telemetry systems. OBJECTIVES: To determine the effect of a cleaning protocol on colonization of surface contaminants on electrocardiographic telemetry systems in 4 cardiovascular step-down units and to compare colonization in medical vs surgical units. METHODS: A prospective, randomized, case-controlled study (the Descriptive Evaluation of Electrocardiographic Telemetry Pathogens [DEET] study) was designed to evaluate microbial colonization on telemetry systems before and after cleaning with sodium hypochlorite wipes. Each randomly selected telemetry system served as its own control. Nurses used a standardized culture technique recommended by personnel in infection control. Colonization before and after cleaning was analyzed by using the McNemar test and frequency tables. A standard cost-comparison analysis was conducted. RESULTS: A total of 30 telemetry systems in medical units and 29 in surgical units were evaluated; 41 telemetry systems (69%) were colonized before the intervention, and 14 (24%) were colonized after it (P < .001). Before cleaning, surface organisms were present in 14 instances (35%) in surgical units and in 27 instances (66%) in medical units (P < .001). The cleaning strategy was cost-effective. CONCLUSIONS: The cleaning intervention was effective, and cost-comparison analysis supported implementing a cleaning strategy for reusable leads rather than investing in disposable leads.

Exposure of RNA templates and encapsidation of spliced viral RNA are influenced by the arginine-rich domain of human hepatitis B virus core antigen (HBcAg 165-173).

Previously, human hepatitis B virus (HBV) mutant 164, which has a truncation at the C terminus of the HBV core antigen (HBcAg), was speculated to secrete immature genomes. For this study, we further characterized mutant 164 by different approaches. In addition to the 3.5-kb pregenomic RNA (pgRNA), the mutant preferentially encapsidated the 2.2-kb or shorter species of spliced RNA, which can be reverse transcribed into double-stranded DNA before virion secretion. We observed that mutant 164 produced less 2.2-kb spliced RNA than the wild type. Furthermore, it appeared to produce at least two different populations of capsids: one encapsidated a nuclease-sensitive 3.5-kb pgRNA while the other encapsidated a nuclease-resistant 2.2-kb spliced RNA. In contrast, the wild-type core-associated RNA appeared to be resistant to nuclease. When arginines and serines were systematically restored at the truncated C terminus, the core-associated DNA and nuclease-resistant RNA gradually increased in both size and signal intensity. Full protection of encapsidated pgRNA from nuclease was observed for HBcAg 1-171. A full-length positive-strand DNA phenotype requires positive charges at amino acids 172 and 173. Phosphorylation at serine 170 is required for optimal RNA encapsidation and a full-length positive-strand DNA phenotype. RNAs encapsidated in Escherichia coli by capsids of HBcAg 154, 164, and 167, but not HBcAg 183, exhibited nuclease sensitivity; however, capsid instability after nuclease treatment was observed only for HBcAg 164 and 167. A new hypothesis is proposed here to highlight the importance of a balanced charge density for capsid stability and intracapsid anchoring of RNA templates.

Stability and morphology comparisons of self-assembled virus-like particles from wild-type and mutant human hepatitis B virus capsid proteins.

Instead of displaying the wild-type selective export of virions containing mature genomes, human hepatitis B virus (HBV) mutant I97L, changing from an isoleucine to a leucine at amino acid 97 of HBV core antigen (HBcAg), lost the high stringency of selectivity in genome maturity during virion export. To understand the structural basis of this so-called "immature secretion" phenomenon, we compared the stability and morphology of self-assembled capsid particles from the wild-type and mutant I97L HBV, in either full-length (HBcAg1-183) or truncated core protein contexts (HBcAg1-149 and HBcAg1-140). Using negative staining and electron microscopy, full-length particles appear as "thick-walled" spherical particles with little interior space, whereas truncated particles appear as "thin-walled" spherical particles with a much larger inner space. We found no significant differences in capsid stability between wild-type and mutant I97L particles under denaturing pH and temperature in either full-length or truncated core protein contexts. In general, HBV capsid particles (HBcAg1-183, HBcAg1-149, and HBcAg1-140) are very robust but will dissociate at pH 2 or 14, at temperatures higher than 75 degrees C, or in 0.1% sodium dodecyl sulfate (SDS). An unexpected upshift banding pattern of the SDS-treated full-length particles during agarose gel electrophoresis is most likely caused by disulfide bonding of the last cysteine of HBcAg. HBV capsids are known to exist in natural infection as dimorphic T=3 or T=4 icosahedral particles. No difference in the ratio between T=3 (78%) and T=4 particles (20.3%) are found between wild-type HBV and mutant I97L in the context of HBcAg1-140. In addition, we found no difference in capsid stability between T=3 and T=4 particles successfully separated by using a novel agarose gel electrophoresis procedure.

Replication advantage and host factor-independent phenotypes attributable to a common naturally occurring capsid mutation (I97L) in human hepatitis B virus.

Mutations of human hepatitis B virus (HBV) occur frequently within the capsid (core) protein in natural infections. The most frequent mutation of the core protein in HBV from Southeast Asia occurs at amino acid 97, changing an isoleucine (I) to a leucine (L). In our systematic study of virus-host interactions, we have examined the replication efficiency of a site-directed mutant, I97L, and its parental wild-type HBV in several different hepatoma cell lines. Interestingly, we found that this capsid variant replicated in human Huh7 hepatoma cells approximately 4.8-fold better than its parental wild-type HBV. A similar phenomenon was observed in another hepatoma cell line, J3. In addition, the level of encapsidated RNA pregenome in mutant I97L was about 5.7-fold higher than that of the wild-type HBV in Huh7 cells. Unlike Huh7 cells, no significant difference in viral DNA replication between the same I97L mutant and its parental wild-type HBV was observed in HepG2, a human hepatoblastoma cell line. This finding of a profound replication advantage for mutant I97L in Huh7 and J3 cells but not in HepG2 cells may have important implications for the emergence of this mutant in chronic HBV carriers. We speculate here that the mutation confers a host factor-independent growth advantage for the survival of HBV variants in gradually dedifferentiating hepatocytes and thus helps prolong viral persistence.