Re-assessing accumulated oxygen deficit in middle-distance runners

The purpose of this study was to re-assess the accumulated oxygen deficit (AOD), incorporating recent methodological improvements i.e., 4 min submaximal tests spread above and below the lactate threshold (LT). We Investigated the Influence of the VO2 -speed regression, on the precision of the estimated total energy demand and AOD. utilising different numbers of regression points and including measurement errors. Seven trained middle-distance runners (mean +/- SD age: 25.3 +/- 5.4y, mass: 73.7 +/- 4.3kg. VO2max 64.4 +/- 6.1 mL x kg(-1) x min(-1)) completed a VO2max, LT, 10 x 4 min exercise tests (above and below LT) and high-intensity exhaustive tests. The VO2 -speed regression was developed using 10 submaximal points and a forced y-intercept value. The average precision (measured as the width of 95% confidence Interval) for the estimated total energy demand using this regression was 7.8mL O2 Eq x kg(-1) x min(-1). There was a two-fold decrease in precision of estimated total energy demand with the Inclusion of measurement errors from the metabolic system. The mean AOD value was 43.3 mL O2 Eq x kg(-1) (upper and lower 95% CI 32.1 and 54.5mL o2 Eq x kg(-1) respectively). Converting the 95% CI for estimated total energy demand to AOD or including maximum possible measurement errors amplified the error associated with the estimated total energy demand. No significant difference in AOD variables were found, using 10,4 or 2 regression points with a forced y-intercept. For practical purposes we recommend the use of 4 submaximal values with a y-intercept. Using 95% CIs and calculating error highlighted possible error in estimating AOD. Without accurate data collection, increased variability could decrease the accuracy of the AOD as shown by a 95% CI of the AOD.     

Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Graves′病患者经~(131)碘治疗后循环活性T细胞亚群的动态观察

本文应用直接、间接双色免疫荧光染色,流体细胞测定仪技术,观察了经~(131)碘治疗的23例Graves′病患者的循环活性T细胞亚群的动态变化。~(131)碘治疗后的第一个月至第三个月,HLA-DR、Ta_1和UCHL_1活性T细胞亚群数目明显增加,以Vicia-villosa为标志的抗抑制细胞亚群较治疗前明显增加。实验结果提示:Graves′病患者经~(131)碘治疗后的抗甲状腺自身抗体浓度增加可能是由于T细胞的激活和抗抑制细胞亚群增加的共同结果。     

Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils

Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as a serine protease, antibiotic, and Wegener's granulomatosis autoantigen) but that share(s) several features: localization in the azurophil granules, a molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, and the ability to degrade elastin. We previously purified one such entity, termed p29b. Using a monospecific antibody, we have cloned from human bone marrow a cDNA encoding the complete p29b protein in its mature form, along with pre- and pro-sequences. The predicted amino acid sequence agrees closely with the NH2-terminal sequence obtained previously from purified p29b, as well as with sequences newly obtained from CNBr fragments. The primary structure is highly homologous to elastase, cathepsin G, T cell granzymes, and other serine proteases, and shares both the catalytic triad and substrate binding pocket of elastase. Hybridization of the full-length cDNA with restriction enzyme digests of human genomic DNA revealed only one fragment. This suggests that the closely related species described previously are the same, and can be subsumed by the term used for the first-described activity, proteinase 3. Proteinase 3 is more abundant in neutrophils than elastase and has a similar proteolytic profile and specific activity. Thus, proteinase 3 may share the role previously attributed to neutrophil elastase in tissue damage, and has the potential to function as an antimicrobial agent.     

The IL-10 polarized cytokine pattern in innate and adaptive immunity cells contribute to the development of FVIII inhibitors

Background

Hemophilia A (HA) is an X-linked inherited bleeding disorder, resulting from a qualitative or quantitative deficiency of clotting factor VIII (FVIII). Antibodies against FVIII, also called inhibitors, block the procoagulant activity of FVIII; thus, impairing hemostatic activity in patients with HA. The exact mechanism underlying the immunological events behind the development of inhibitors remains unknown. This study aimed to understand immune response to FVIII in patients with HA who were either positive [HAα-FVIII(+)] or negative [HAα-FVIII(−)] for inhibitors.

Methods

Cytokine profiles [interferon-γ (IFN − γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, and IL-10] of innate and adaptive immune cells present in the peripheral blood of participants were characterized.

Results

Presence of inhibitors was significantly associated with decreased frequencies of TNF-α-positive monocytes and neutrophils, IL-5-positive monocytes, IL-4-positive neutrophils, and increased frequencies of IL-10-positive neutrophils and T cells. T cells from HAα-FVIII(−) patients expressed increased levels of almost all cytokines. In contrast, HAα-FVIII(+) patients showed lower levels of all cytokines in CD4⁺ and CD8⁺ T cells, except IL-10. B cells from HAα-FVIII(−) patients expressed increased levels of IL-4 while those from HAα-FVIII(+) patients expressed increased levels of IL-10.

Conclusions

The global cytokine profiles of innate and adaptive immune cells showed an anti-inflammatory/regulatory pattern in HAα-FVIII(+) patients and a mixed pattern, with a bias toward inflammatory cytokine profile, in HAα-FVIII(−) patients. The occurrence of these profiles seems to be associated with presence FVIII inhibitors.     

Antibiotic proteins of human polymorphonuclear leukocytes.

Nine polypeptide peaks with antibiotic activity were resolved from human polymorphonuclear leukocyte azurophil granule membranes. All but 1 of the 12 constituent polypeptides were identified by N-terminal sequence analysis. Near quantitative recovery of protein and activity permitted an assessment of the contribution of each species to the overall respiratory-burst-independent antimicrobial capacity of the cell. Three uncharacterized polypeptides were discovered, including two broad-spectrum antibiotics. One of these, a defensin that we have designated human neutrophil antimicrobial peptide 4, was more potent than previously described defensins but represented less than 1% of the total protein. The other, named azurocidin, was abundant and comparable to bactericidal permeability-increasing factor in its contribution to the killing of Escherichia coli.