Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB

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Human herpesvirus 8 infection among various population groups in southern Israel

OBJECTIVE: To compare the prevalence of antibodies to human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus among Israeli and Ethiopian subjects. METHODS: Serum samples were obtained from 98 Israeli Jewish students aged 18-30 years, 100 HIV-1-seronegative Ethiopian immigrants to Israel of the same age, and 100 HIV-1-seronegative Ethiopian children 1-12 years old upon their arrival in southern Israel. Plasma samples were obtained from 3 hospitalized patients with multicentric Castleman disease (MCD) as positive controls. All serum samples were tested for antibodies to both latent and lytic antigens. Antibodies to the lytic antigens and the latency-associated nuclear antigen (LANA) of HHV-8 were detected by enzyme linked immunosorbent assay and by immunofluorescence assay. HHV-8 DNA from serum or plasma samples was detected by polymerase chain reaction analysis. RESULTS: Antibodies to HHV-8 LANA were detected in 2.9% of the Israeli subjects aged 18-30 years and in 26% of the Ethiopian subjects from both age groups tested. Antibodies to the lytic antigens were detected in all 3 MCD patients, in 4% of the Ethiopian children, and in 2% of the 18- to 30-year-old Ethiopians. No antibodies to the lytic antigens were detected in the Israeli students. HHV-8 DNA was detected in all 3 MCD patients and in 2 of 4 of the Ethiopian children positive for the lytic antigens. CONCLUSIONS: HHV-8 is highly prevalent in Ethiopian immigrants to Israel as compared with Israeli students. Antibodies to HHV-8 in Ethiopia are acquired before puberty. The results of this study indicate the association of HHV-8 with MCD, as has been documented by many other researchers.     

Consensus guidelines on analgesia and sedation in dying intensive care unit patients

Background

Intensivists must provide enough analgesia and sedation to ensure dying patients receive good palliative care. However, if it is perceived that too much is given, they risk prosecution for committing euthanasia. The goal of this study is to develop consensus guidelines on analgesia and sedation in dying intensive care unit patients that help distinguish palliative care from euthanasia.

Methods

Using the Delphi technique, panelists rated levels of agreement with statements describing how analgesics and sedatives should be given to dying ICU patients and how palliative care should be distinguished from euthanasia. Participants were drawn from 3 panels: 1) Canadian Academic Adult Intensive Care Fellowship program directors and Intensive Care division chiefs (N = 9); 2) Deputy chief provincial coroners (N = 5); 3) Validation panel of Intensivists attending the Canadian Critical Care Trials Group meeting (N = 12).

Results

After three Delphi rounds, consensus was achieved on 16 statements encompassing the role of palliative care in the intensive care unit, the management of pain and suffering, current areas of controversy, and ways of improving palliative care in the ICU.

Conclusion

Consensus guidelines were developed to guide the administration of analgesics and sedatives to dying ICU patients and to help distinguish palliative care from euthanasia.     

Defects in regulation of apoptosis in caspase-2-deficient mice

During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.     

Replication of a type I avian adenovirus (CELO) mutant in the chicken embryo

Summary Replication of a CELO large plaque (LP) mutant and that of its wild type small plaque (SP) parent was studied in the chorioallantoic membrane (CAM) and in the amnion of 11-day-old embryos. Although both strains produced essentially the same amount of virus in the tissue fluids, they differed in their rates of replication. Replication of the SP parent was maximal in the CAM 24 to 48 hours before that of the LP mutant. Whereas inclusions were observed in SP inoculated CAM 48 hours PI and were present during the course of study; LP inclusions were rare at 72 hours PI and thereafter; LP inclusions were seen at 72 hours PI. Fewer SP than LP particles were required to produce inclusions. No inclusions were seen in sections of the trachea and liver removed at 96 hours PI from embryos inoculated via the amniotic sac with LP and SP virus.Contribution 1466 of the Rhode Island Agriculture Experimental Station.     

Antibiotic prescribing and admissions with major suppurative complications of respiratory tract infections: a data linkage study.

BACKGROUND: Systematic reviews of antibiotic treatment of common acute respiratory tract infections (RTIs) suggest modest symptomatic benefit, but provide limited evidence that prescribing prevents complications. AIM: To assess the relationship between penicillin prescribing (the most commonly used group of antibiotics for RTIs) and hospital admission with complications. DESIGN OF STUDY: Data linkage study. SETTING: Ninety-six health authorities of England for the year 1997-1998. METHOD: Hospital admissions related to RTIs were linked with prescribing analysis and cost (PACT) data. RESULTS: There was close correlation between items of penicillin use and total antibiotic use (r = 0.96). After controlling for SMR, age, sex, and Townsend score, a one-unit increase in penicillin use (items dispensed per capita) was associated with a reduction in annual incidence per 10,000 of admissions for quinsy (-3.55 admissions, 95% confidence interval [CI] = -6.85 to -0.26), and mastoiditis (square root of incidence of admissions = -1.05, 95% CI = -1.82 to -0.27). This does not represent lower referral thresholds among higher prescribers as higher prescribing was associated with more admissions for tonsillectomy and overall admissions. Increasing prescribing by 2000 items of penicillin for a practice of 10,000 patients could possibly prevent one admission for either mastoiditis or quinsy. CONCLUSION: Higher antibiotic prescribing is associated with significantly fewer admissions with major complications. However, the overall size of the effect is modest and it is difficult to advocate an overall increase in prescribing to prevent complications. Future research should concentrate on finding better methods of targeting antibiotics to individuals at risk of poor outcome.     

Molecular Epidemiology of Ampicillin-Resistant Non-β-Lactamase-Producing Haemophilus influenzae

Resistance to ampicillin without β-lactamase production is not a frequent occurrence among Haemophilus influenzae strains. This kind of resistance is encountered in unencapsulated strains isolated from bronchial secretions and ear, nose, and throat specimens and is exceptional in H. influenzae type b. We studied 29 of these strains from various areas in France and 2 reference strains. Strains were compared by using ribotyping, arbitarily primed PCR with two primers, and pulsed-field gel electrophoresis. Each technique enabled the identification of 20 to 23 different patterns among the 31 strains. The combination of the different patterns for the strains obtained by the different techniques provided 27 distinct profiles. According to these results, it seems that the clonal propagation of these resistant strains does not occur.     

Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific,unrestricted cytotoxic T cells

Cytotoxic T cells (CTL) recognize target proteins as short peptides presented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T cell receptor (TCR) recognition of target proteins and non-protein structures. How such T cell responses are generated is presently unclear. We generated carbohydrate (CHO)-specific, MHC-unrestricted CTL responses by coupling di- and trisaccharides to K^b- or D^b-binding peptides for direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central positions on the carrier peptide. With two of these glycopeptides, with galabiose (Galα1-4Gal; Gal₂) bound to a homocysteine (via an ethylene spacer arm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-derived peptide (RGYVYQGL binding to K^b), CTL were generated which preferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal₂ epitope in a glycolipid. By fractionation of CTL, preliminary data indicate that glycopeptide-specific K^b-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The results demonstrate that hapten-specific unrestricted CTL responses can be generated with MHC class I-binding carrier peptides. Different models that might explain the generation of such responses are discussed.     

Antibody against the carboxyl terminus of intimin alpha reduces enteropathogenic Escherichia coli adherence to tissue culture cells and subsequent induction of actin polymerization

The C-terminal third of intimin binds to its translocated receptor (Tir) to promote attaching and effacing lesion formation during infection with enteropathogenic Escherichia coli (EPEC). We observed that the adherence of EPEC strains to HEp-2 cells was reduced and that actin polymerization was blocked by antibody raised against the C-terminal third of intimin alpha.