Linkage disequilibria between HLA-B and the rarer properdin factor B alleles, BfF1 and BfS1

Phenotypic association and highly significant linkage disequilibria have been demonstrated for HLA-B18 and Bf^F1 and HLA-Bw50 and Bf^S1 alleles among Caucasians from Australia and the United States (San Francisco Bay area). The HLA-B18, Bf^uF1 association appears to be associated with HLA-Aw30. It is possible that Bf^S1 as a mutation, after the evolutionary splitting of HLA-Bw21, on an HLA-Bw50 haplotype, and that Bf^F1 arose on an HLA-Aw30, B18 haplotype.     

Family studies of the HLA system in acute post-streptococcal glomerulonephritis

Eighteen families (67 siblings) of index cases with acute post-streptococcal glomerulonephritis (APSGN) were typed for HLA-A,B,C,DR antigens. Twenty cases of clinical nephritis and 10 cases of asymptomatic disease were detected among the sibships. In eight families with more than one affected individual comprising 18 sib pairs random segregation of paternal and maternal HLA haplotypes was found (0.5 < p < 0.6), but some antigens (CW1, DR3) showed deviation from the expected 1:1 ratio in affected and nonaffected siblings in backcross families. We had previously noticed the existence of Mendelian recessive ratios in APSGN but in the absence of clear evidence for a dominant or recessive mode of inheritance for a putative APSGN susceptibility gene(s), pedigree data were analyzed twice for linkage with HLA using the two genetic models. The data obtained, although not sufficient to reject the hypothesis of linkage, provide no support for it. Comparison of the frequency of 61 HLA antigens among 42 unrelated APSGN patients and 109 controls, showed that HLA-DRW4 is more frequent among the former (p_c = 0.0500).     

Alloantigen-specific T-cell anergy induced by human keratinocytes is abrogated upon loss of cell-cell contact

The activation of primary human T cells largely depends on the expression of both major histocompatibility complex (MHC) class II and B7 molecules on antigen-presenting cells (APC), whereas APC expressing HLA class II but not B7 antigens are expected to induce anergy. According to this concept, interferon-γ (IFN-γ)-activated keratinocytes (KC) expressing HLA class II but not B7 costimulatory antigens should be able to induce anergy. However, in terms of anergy versus activation contradicting data have been published on the outcome of interaction between T cells and human KC. In addition, it has been shown that human KC can express a B7-like molecule with unknown function, whereas MHC expression may be functionally impaired. To evaluate this item we transfected the human A431 KC cell line with B7-1 coding sequences and up-regulated HLA-DR by treatment with IFN-γ, yielding A431^DR,B7-1 cells. Irradiated A431^DR,B7-1 cells were found to be capable of inducing vigorous proliferative primary T-cell responses in resting allogeneic T cells, whereas A431^DR cells could induce proliferation only when interleukin-2 (IL-2) was added. These data indicate that KC can present alloantigens, and that lack of costimulatory molecules on KC is the main reason why these cells cannot induce primary T-cell responses. Surprisingly, however, no evidence could be obtained of stable anergy induction by A431^DR cells, as T cells contacted with A431^DR cells and then transferred to A431^DR,B7-1 cells clearly demonstrated alloresponsiveness. T-cell non-responsiveness was maintained only when T cells remained in contact with A431^DR cells. These data indicate that, despite expression of HLA class II in the absence of B7 costimulatory molecules, human KC cannot induce stable anergy but rather induce short-term anergy in primary resting T cells.     

Ex vivo detection of adenovirus specific CD4 T-cell responses to HLA-DR-epitopes of the Hexon protein show a contracted specificity of THELPER cells following stem cell transplantation

Human adenovirus (HAdV) is a cause of significant morbidity and mortality in immunocompromised patients, especially after stem cell transplantation (SCT). Viral clearance has been attributed to CD4⁺ T-cell responses against the Hexon-protein, but the frequency of specific T_HELPER cells is extremely low or not detectable ex vivo and preference for different CD4⁺ T-cell epitopes is variable among individuals. We therefore analyzed 44 healthy donors and 6 SCT-recipients for Hexon-specific CD4⁺-responses ex vivo, to identify epitopes which would be broadly applicable. We selected 19 candidate epitopes with predicted restriction to HLA-DR1/DR3/DR4/DR7; 16 were located within the highly conserved regions, indicating cross-reactivity of T cells among HAdV-subspecies. Ten epitopes induced CD4⁺-proliferation in >50% of individuals, confirmed by intracellular IFN-γ detection. Three SCT recipients who recovered from an infection with HAdV displayed reactivity towards only a single hexon epitope, whereas healthy individuals were responsive to two to eight epitopes (median 3). The ex vivo detection of Hexon-specific CD4⁺ T-cells, without any long-term culture in vitro, enables the detection and generation of HAdV-specific CD4⁺ T cells for adoptive T-cell transfer against HAdV-infection post SCT.     

Influence of individual energy cost on running capacity in warm, humid environments

Purpose

Challenging environmental conditions including heat and humidity are associated with particular risks to the health of runners and triathletes during prolonged events. The heat production of a runner is the product of its energy cost of running (C _r) by its velocity. Since C _r varies greatly among humans, those individuals with high C _r are more exposed to heat stress in warm and humid conditions. Although risk factor awareness is crucial to the prevention of heat stroke and potential fatalities associated therewith, how C _r affects the highest sustainable velocity (V) at which maximal heat loss matches heat production has not been quantified to date.

Methods

Here, we computed in virtual runners weighting 45–75 kg, the influence of C _r variability from 3.8 to 4.4 J·m^?1·kg^?1 on V. Heat loss by radiation, convection, and conduction was assessed from known equations including body dimensions, running velocity (3.4–6.2 m·s^?1), air temperature (T _a, 10–35 °C) and relative humidity (r _h, 50, 70 and 90 %).

Results

We demonstrated a marked and almost linear influence of C _r on V in hot and humid conditions: +0.1 J·kg^?1·m^?1 in C _r corresponded to ?4 % in V. For instance, in conditions 25 °C r _h 70 %, 65-kg runners with low C _r could sustain a running speed of 5.7 m·s^?1 as compared to only 4.3 m·s^?1 in runners with high C _r, which is huge.

Conclusion

We conclude that prior knowledge of individual C _r in athletes exposed to somewhat warm and humid environments during prolonged running is one obvious recommendation for minimizing heat illness risk.     

The molecular basis for HLA class II associations with rheumatoid arthritis

The association of HLA-DR4 with rheumatoid arthritis strongly implicates genes of the major histocompatibility complex (MHC) as contributing to disease susceptibility. Molecular analysis of MHC genes expressed on haplotypes in association with HLA-DR4 reveals that at least six different alleles of the DR₁ locus and at least three different alleles of the DQ locus occur on different DR4+ haplotypes. Some of these allelic differences are quite substantial, and others are rather subtle, involving as few as two amino acids. The analysis of individual DR and DQ alleles in rheumatoid arthritis identifies some DR4+ genes strongly associated with disease susceptibility and some DR4+ genes which are not. The Dw4(DR4) and Dw14(DR4) DR₁ genes appear to represent specific alleles which confer disease risk in RA; other DR₁ genes, such as Dw10(DR4), may represent DR genes altered during evolution which have lost their contribution to RA susceptibility. DQ 3.1(DQw3) and DQ 3.2(DQw3) DQ genes, which are present on DR4+ haplotypes, represent discrete variable alleles not directly implicated in RA, but which account for HLA-DR4 associations with other diseases, such as the association of DQ 3.2(DQw3) with Type I diabetes.     

Comparison of Serum and Cell-Specific Cytokines in Humans

Cytokines function at the cellular, microenvironmental level, but human cytokine assessment is most commonly done at the macro level, by measuring serum cytokines. The relationships between serum and cellular cytokines, if there are any, are undefined. In a study of hospitalized patients in Malawi, we compared cytometrically assessed, cell-specific cytokine data to serum interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) levels in 16 children and 71 (IL-2, -4, -6, -10) or 159 (IL-8, IFN-γ, and TNF-α) adults, using Wilcoxon rank sum tests and Pearson's (r_p) and Spearman's (r_s) rank correlations. For the entire study group, correlations between identical serum and cellular cytokines mainly involved IL-8 and IFN-γ, were few, and were weakly positive (r < 0.40). Blood culture-positive persons had the most and strongest correlations, including those between serum IL-2 levels and the percentages of lymphocytes spontaneously making IL-2 (r_s = +0.74), serum IL-8 levels and the percentages of lymphocytes spontaneously making IL-8 (r_p = +0.66), and serum IL-10 levels and the percentages of CD8⁺ T cells making TNF-α (r_p = +0.89). Human immunodeficiency virus (HIV)-positive persons had the next largest number of correlations, including several serum IL-8 level correlations, correlation of serum IL-10 levels with the percentages of lymphocytes producing induced IL-10 (r_s = +0.36), and correlation of serum IFN-γ levels and the percentages of lymphocytes spontaneously making both IL-6 and IFN-γ in the same cell (r_p = +0.59). HIV-negative, malaria smear-positive, and pediatric patients had few significant correlations; for the second and third of these subgroups, serum IL-8 level was correlated with the percentage of CD8⁻ T cells producing induced IL-8 (r_s = +0.40 and r_s = +0.56, respectively). Thus, the strength of associations between serum and cellular cytokines varied with the presence or absence of bloodstream infection, HIV status, and perhaps other factors we did not assess. These results strongly suggest that serum cytokines at best only weakly reflect peripheral blood cell cytokine production and balances.     

Is there any association between leptin levels and bone mineral density in haemophiliac men?

Introduction

Conflicting data exist regarding the role of leptin in bone metabolism. The purpose of the present study was to investigate serum leptin concentrations in male patients with haemophilia A and B, a disease known to be associated with low bone mass.

Material and methods

Eighty-one male patients, aged 45.4 ±15 years, were screened. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN) and total hip (TH).

Results

Low bone mass was diagnosed in 20 patients (24.7%). Serum leptin concentrations were strongly associated with body weight (r _s = 0.457, p = 0.0001) and body mass index (BMI) (r _s = 0.491, p = 0.0001). In unadjusted analysis leptin was inversely associated with BMD in LS (r _s = –0.255, p = 0.023), but not in FN and TH (r _s = –0.205, p = 0.068 and r _s = –0.191, p = 0.090, respectively). However, after adjusting for BMI and body weight, leptin was inversely associated with BMD in FN (F _1,76 = 7.727, p = 0.007, β = –0.371, ΔR ² = 0.089) and TH (F _1,76 = 4.533, p = 0.036, β = –0.290, ΔR ² = 0.054), but not in LS (F _1,75 = 2.076, p = 0.154, β = –0.202, ΔR ² = 0.026). No association was found between age, presence of HBV, HCV or HIV infection or alkaline phosphatase and leptin levels.

Conclusions

Our study showed a negative association between circulating leptin levels and bone mass in males, independently of body weight and BMI.     

The susceptible HLA class II alleles and their presenting epitope(s) in Goodpasture's disease

Goodpasture's disease is closely associated with HLA, particularly DRB1*1501. Other susceptible or protective HLA alleles are not clearly elucidated. The presentation models of epitopes by susceptible HLA alleles are also unclear. We genotyped 140 Chinese patients and 599 controls for four‐digit HLA II genes, and extracted the encoding sequences from the IMGT/HLA database. T‐cell epitopes of α3(IV)NC1 were predicted and the structures of DR molecule‐peptide—T‐cell receptor were constructed. We confirmed DRB1*1501 (OR = 4·6, P = 5·7 × 10⁻²⁸) to be a risk allele for Goodpasture's disease. Arginine at position 13 (ARG13) (OR = 4·0, P = 1·0 × 10⁻¹⁷) and proline at position 11 (PRO11) (OR = 4·0, P = 2·0 × 10⁻¹⁷) on DRβ1, encoded by DRB1*1501, were associated with disease susceptibility. α_134–148 (HGWISLWKGFSFIMF) was predicted as a T‐cell epitope presented by DRB1*1501. Isoleucine₁₃₇, tryptophan₁₄₀, glycine₁₄₂, phenylalanine₁₄₃ and phenylalanine₁₄₅, were presented in peptide‐binding pockets 1, 4, 6, 7 and 9 of DR2b, respectively. ARG13 in pocket 4 interacts with tryptophan₁₄₀ and forms a hydrogen bond. In conclusion, we propose a mechanism for DRB1*1501 susceptibility for Goodpasture's disease through encoding ARG13 and PRO11 on MHC‐DRβ1 chain and presenting T‐cell epitope, α_134–148, with five critical residues.     

The CD4+ T‐cell epitope‐binding register is a critical parameter when generating functional HLA‐DR tetramers with promiscuous peptides

Detection of CD4⁺ T cells specific for tumor‐associated antigens is critical to investigate the spontaneous tumor immunosurveillance and to monitor immunotherapy protocols in patients. We investigated the ability of HLA‐DR^*1101 multimers to detect CD4⁺ T cells specific for three highly promiscuous MAGE‐A3 derived peptides: MAGE‐A3_191–205 (p39), MAGE‐A3_281–295 (p57) and MAGE‐A3_286–300 (p58). Tetramers stained specific CD4⁺ T cells only when loaded with p39, although all peptides activated the specific T cells when presented by plastic‐bound HLA‐DR^*1101 monomers. This suggested that tetramer staining ability was determined by the mode rather than the affinity of peptide binding to HLA‐DR^*1101. We hypothesized that peptides should bear a single P1 anchor residue to bind all arms of the multimer in a homogeneous register to generate peptide‐HLA‐DR conformers with maximal avidity. Bioinformatics analysis indicated that p39 contained one putative P1 anchor residue, whereas the other two peptides contained multiple ones. Designing p57 and p58 analogues containing a single anchor residue generated HLA‐DR^*1101 tetramers that stained specific CD4⁺ T cells. Producing HLA‐DR^*1101 monomers linked with the optimized MAGE‐A3 analogues, but not with the original epitopes, further improved tetramer efficiency. Optimization of CD4⁺ T‐cell epitope‐binding registers is thus critical to generate functional HLA‐DR tetramers.     

Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children

The function of CD4⁺ T cells with regulatory activity (T_regs) is the down-regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV-1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV-1 disease. We evaluated the correlation between viral load, immune activation and T_regs in HIV-1-infected children. Eighty-nine HIV-1-infected children (aged 6–14 years) were included in the study and analysed for HIV-1 plasmaviraemia, HIV-1 DNA load, CD4 and CD8 cell subsets. T_reg cells [CD4⁺ CD25^highCD127^lowforkhead box P3 (FoxP3^high)] and CD8-activated T cells (CD8⁺CD38⁺) were determined by flow cytometry. Results showed that the number of activated CD8⁺CD38⁺ T cells increased in relation to HIV-1 RNA plasmaviraemia (r = 0·403, P < 0·0001). The proportion of T_regs also correlated positively with HIV-1 plasmaviraemia (r = 0·323, P = 0·002), but correlated inversely with CD4⁺ cells (r = −0·312, P = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4⁺ depletion. Interestingly, a positive correlation was found between the levels of T_regs and CD8⁺CD38⁺ T cells (r = 0·305, P = 0·005), and the percentage of T_regs tended to correlate with HIV-1 DNA load (r = 0·224, P = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of T_reg cells. In turn, the suppressive activity of T_regs may impair effector responses against HIV-1, but appears to be ineffective in limiting immune activation.     

The oxygen consumption of mammalian non-myelinated nerve fibres at rest and during activity

1. A study has been made of the oxygen consumption of non-myelinated nerve fibres of rabbit desheathed cervical vagus nerves at rest and during activity.2. The average resting oxygen consumption (Q_r) was 0·0924 μmole/g. min at 21° C. Stimulation for 1-3 min at 3/sec caused an extra oxygen consumption (Q_s) of 816 p-mole/g.shock.3. When the frequency of stimulation was increased, to 10/sec and 30/sec, Q_s fell. When the frequency was decreased, to 1/sec and 0·3/sec, Q_s increased slightly.4. When the temperature was decreased, Q_r fell; when the temperature was increased, Q_s also increased. Temperature similarly affected Q_s with high frequencies of stimulation, but had relatively little effect on Q_s at low frequencies of stimulation.5. An isolated single shock seemed to produce an increase in oxygen consumption of about 1200 p-mole/g, and this value was largely independent of temperature.6. When part of the sodium in the Locke solution was replaced by barium, Q_r decreased (by 12%) whereas Q_s increased (by 87%).7. Veratrine (1 μg/ml.) increased both Q_r (by 142%) and Q_s (by 361%).8. Acetylcholine (1·7 mM) increased Q_r (by 32%).9. When nerves were transferred to potassium-free solutions there was little change in Q_r, and Q_s fell slightly (by 8%).10. When the potassium concentration in the Locke solution was increased 4-fold, Q_r increased (by 27%).11. Salicylate (1-10 mM) increased Q_r (by 24%) and abolished Q_s.12. When the sodium of Locke solution was replaced by lithium, Q_r decreased (by 19%) and Q_s was abolished.13. In sodium-Locke solution ouabain (100 μM) decreased Q_r (by 26%) and abolished Q_s. In lithium-Locke solution ouabain also decreased Q_r (by 28%).14. All or nearly all of the oxygen consumed at rest or during activity seemed to be used to pump potassium ions into, and sodium ions out of, the axoplasm.15. The K/O₂ ratio during pumping was about 5·0.     

Up-regulation of human epidermal Langerhans' cell B7-1 and B7-2 co-stimulatory molecules in vivo by solar-simulating irradiation

Ultraviolet (UV) radiation impairs cutaneous immune functions and induces antigen-specific tolerance both locally at the irradiated skin site, as well as at distant skin sites and systemically. It has been postulated that in the local model, altered Langerhans' cells (LC) provide tolerogenic signals, and studies in vitro have indicated that UV radiation may down-regulate the expression of co-stimulatory molecules on the surface of these cells. To examine the effect of UV radiation on LC co-stimulatory molecules in vivo, we irradiated human volunteers with erythematogenic doses of solar-simulating UV radiation (SSR), and analyzed the expression of cell surface markers in dermatome skin samples obtained 1–72 h post-irradiation. For flow cytometric analysis, epidermal cell (EC) suspensions were prepared and double labeled with monoclonal antibodies against CD1a or HLA-DR, and B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), ICAM-3 (CD50), LFA-3 (CD58), E-cadherin, or integrin-β₄ (CD104). In unirradiated control skin samples, keratinocytes (KC) expressed high levels of E-cadherin. LC expressed high levels of both E-cadherin and ICAM-3, and low levels of B7-2, LFA-3, ICAM-1, and integrin-β₄. Following SSR, a triphasic reaction pattern was seen: an immediate, down-regulatory phase prevailing 2–6 h post-irradiation, when the number of DR⁺ and CD1a⁺ cells were temporarily reduced; a delayed, up-regulatory phase in which the number of LC was increased and the expression intensities of CD1a, HLA-DR, B7-1, and B7-2 were strongly up-regulated, maximally evident 12–24 h after irradiation, but no more seen at 48 h; and a late phase at 72 h, in which an influx of monocytes and a concomitant rise in DR⁺ cells was recorded. We conclude that to understand real-life cutaneous UV immunology, studies in vitro need to be complemented with studies in vivo. In the case of LC, the effects of erythematogenic UV radiation in vivo on human LC B7 co-stimulatory molecules include an up-regulatory stage.     

HLA-DR antigens in Chinese-American families

This paper contains results of a study on HLA-DR antigens in Chinese-American families. DR2, DR4, DRw9, and DRw6Y were the most common DR specificities encountered, and DR1 occurred with the lowest frequency. All recognized DR antigens were observed. The frequency of a blank allele was 6.4–12.8%. Weak serologic reactions with sera primarily of Caucasian origin were not infrequently observed. These findings suggested that ethnic-related antigens were present in this population. Two families showed segregation of a new serologic pattern based on polyspecific sera. The gene frequencies of the Bf^F allele and the GLO¹ allele were low as compared to Caucasians. A method is described for improving the yield of viable B cells from frozen B-lymphocyte preparations.     

HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM)

The Basques were previously shown to present a high frequency of HLA—B18 and Bf Fl. which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA- A1, Bw57, Bf S, C4 FIS, DR7 and HLA- Aw30, Cw5, B18, Bf Fl, C4 Fs°, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA— DR3 : a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1. P < 10⁻¹¹). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%). and HLA—DR2 was not found. The silent allele C4 s ° was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P < 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.     

Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

Several studies correlated genetic background and pancreatic islet-cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and β cell function. This characterization has a potential importance with regard to T1AD patients'' stratification and follow-up in therapeutic prevention. In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1β, tumour necrosis factor (TNF)-α, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0·80; P = 0·000), IL-8 and TNF-α (r = 0·60; P = 0·000); IL-8 and IL-12 (r = 0·57; P = 0·001) and TNF-α and IL-12 (r = 0·93; P = 0·000). Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = −0·45; P = 0·011) and CCL2 (r = −0·65; P = 0·000), while IA-2A showed a negative correlation with IL-10 (r = −0·38; P = 0·027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. In summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA-2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre-T1AD phase could help to explain the mechanistic of the well-known role of IA-2A as a more specific marker of beta-cell damage than GADA during the natural history of T1AD.     

The TRH stimulation test in subtypes of unipolar depression

The thyrotropin releasing hormone (TRH) stimulation test was administered to 54 primary unipolar endogenously depressed and 19 non-depressed hospitalized inpatients. Blunted TSH reponses to TRH infusion (Δ_max TSH<7 μU/ml) were revealed in 18 depressed and no non-depressed patients (P<0.01). Augmented TSH responses (Δ_max TSH>23 μU/ml) were noted in 8 depressed and no non-depressed patients (P = n.s.). The TRH stimulation test did not distinguish between subtypes of unipolar depression using the familial subtyping criteria of Winokur. These findings are discussed in light of previously reported dexamethasone suppression test subtype distinctions.     

Hospice nurse identification of comfortable and difficult discussion topics: Associations among self-perceived communication effectiveness,nursing stress,life events,and burnout

ObjectiveTo assess hospice nurses’ self-perceived communication effectiveness, identify comfortable and difficult discussion topics, and explore associations between self-perceived communication effectiveness, burnout, nursing stress, and life events.Methods181 nurses completed self-report measures, then listed comfortable and/or difficult patient and caregiver discussion topics.ResultsNurses were generally experienced (median 9 years, range <1–46 as a registered nurse; median 3 years, range <1–23 as a hospice nurse), reporting overall Effective/Very Effective communication skills (85.6%); 70% desired more communication training. As nursing stress increased perceived overall communication effectiveness decreased (r_s = ?0.198; p 0.012). As burnout increased overall effectiveness (r_s = ?0.233; p 0.002) and effectiveness with difficult topics (r_s = ?0.225; p 0.003) decreased. Content analysis revealed 9 categories considered both comfortable and difficult to discuss; contextual comments provided fuller explanation (e.g. providing general information on the Dying Process was comfortable, discussing Dying process during patient death was difficult). Seven additional categories (e.g. Denial) were deemed uniquely difficult.ConclusionHospice nurses perceive themselves as effective communicators, yet want additional training. Perceived communication effectiveness is associated with burnout and stress.Practice implicationsCommunication training that focuses on contextually grounded topics identified by participants may optimize communication between hospice nurses, patients and caregivers.     

The ability of H to modulate C5 utilization by the cell-bound alternative pathway C5 convertase differs on sheep and rabbit erythrocytes

The ability of H to inhibit formation of the alternative pathway C3 convertase differs on the non-activating cells sheep erythrocytes (E^s) and on the activating cells rabbit erythrocytes (E^r) or desialated sheep erythrocytes (E^des). C3 convertase sites are converted to C5 convertase sites by deposition of additional C3b molecules and C5 binds to cell-bound C3b in a reaction that is inhibited by H. C5 convertase sites P(C3b)_nBb were formed on E^s, E^r, E^des and revealed by incubation of the cells with purified C5 and with rat serum treated with KSCN and hydrazine. When incremental amounts of H were added to the reaction, a dose-dependent inhibition of C5 utilization was observed. The amount of H that inhibited 50% of C5 utilization was the same for a given cell regardless of the number of C5 convertase sites that were expressed on the cell. However the 50% inhibitory dose of H was 92 ng/10⁷ E^sP(C3b)_nBb, 87 ng/10⁷ E^desP(C3b)_nBb while it was at least 380 ng/10⁷ E^rP(C3b)_nBb. These results suggest that H competes with C5 for uptake within the C5 convertase site and that the regulatory effect of H on C5 cleavage depends on the surface to which the convertase is bound.     

Carbon dioxide storage and nonbicarbonate buffering in the human body before and after an Himalayan expedition

Before and 7–12 days after an Himalayan expedition CO₂ equilibration curves were determined in the blood plasma of 12 mountaineers by in vitro and in vivo CO₂ titration; in vivo osmolality changes (ΔOsm?·?ΔPCO₂ ^?1, ΔOsm?·?ΔpH^?1, where PCO₂ is the partial pressure of CO₂) during the latter experiments yielded estimates of whole body CO₂ storage. In vitro ?Δ[HCO₃ ^?]?·?ΔpH^?1 [nonbicarbonate buffer capacity (β) of blood] was increased 7 days after descent [before 31.3 (SEM 0.4) mmol?·?kgH₂O^?1, after?38.3?(SEM 3.9)?mmol?·?kgH₂O^?1; P<0.05] resulting from an increased proportion of young erythrocytes; in additional experiments an augmented β was found in young (low density cells) compared to old cells [<1.097 g?·?ml^?1: 0.216 (SEM 0.028) mmol?·?gHb^?1, >1.100?g?·?ml^?1: 0.145?(SEM 0.013)?mmol?·?gHb^?1, where Hb is haemoglobin; P<0.02]. In spite of increased Hb mass in vivo Δ[CO_2total]?·?ΔPCO₂ ^?1 [0.192?(SEM 0.010)?mmol?·?kgH₂O^?1?·?mmHg^?1] and ?Δ[HCO₃ ^?]?·?ΔpH^?1 [17.9?(SEM 1.0)?mmol?·?kgH₂O^?1] as indicators of extracellular β rose only slightly after altitude (7 days +16%, P<0.02; +7%, NS) because of haemodilution. The ΔOsm?·?ΔPCO₂ ^?1 [0.230?(SEM 0.015) mosmol?·?kgH₂O^?1?·?mmHg^?1] remained unchanged. Prealtitude differences in ΔOsm?·?ΔpH^?1 between hypercapnia [?41?(SEM 5)?mosmol?·?kgH₂O^?1] and hypo-capnia [?20?(SEM 3)?mosmol?·?kgH₂O^?1; P<0.01] disappeared temporarily after return since the former slope was reduced. The high value during hypercapnia before ascent probably resulted from mechanisms stabilizing intracellular pH during moderate hypercapnia which were attenuated after descent.