The set of naturally processed peptides displayed by DR molecules is tuned by polymorphism of residue 86

The response to tetanus toxoid (TT) was studied in immune donors that carry two alleles of DR5 that differ only at DRβ residue 86: DRB1*1101 (G86, abbreviated 1101) and DRB1*1104 (V86, abbreviated 1104). A large number of TT-specific T cell clones was isolated and the epitopes recognized in association with 1101 and 1104 were mapped. We found that two epitopes (p2 and p32) can be recognized in association with both 1101 and 1104 while three epitopes (p23, p27 and p30) are recognized in association with 1101, but never in association with 1104. The sets of naturally processed self peptides displayed by 1101 and 1104 were characterized using alloreactive T cell clones. We found that all 1104 alloreactive clones recognize both 1104 and 1101, while ?30% of the alloreactive 1101 clones fail to recognize 1104. Thus it is apparent that both naturally processed TTand self peptides displayed on 1104 molecules represent a fraction of those displayed on 1101 molecules. The mechanism responsible for this differential presentation was investigated by comparing the capacity of 1101 and 1104 antigen-presenting cells to present TTor synthetic peptides to specific T cells and by measuring the binding of these peptides to DR molecules. Three sets of results suggest that V86 acts as a constraint to the binding of naturally processed peptides: (i) all 1104-restricted or alloreactive T cell clones recognize TT- or allo-epitopes presented by 1101 as well, thus ruling out a major effect of V86 as a residue determining T cell restriction specificity; (ii) presentation of naturally processed peptides correlates in general with the capacity of long synthetic peptides to bind to 1101 or 1104 and (iii) while the naturally processed p30 epitope discriminates between 1101 and 1104, a short synthetic peptide binds equally well to and is comparably recognized in association with both 1101 and 1104. Taken together these results suggest that the natural polymorphism at residue 86 might be a molecular switch that finely tunes the complexity of the peptide collection presented on DR molecules.     

Local cerebral blood flow in gently restrained rats: effects of propranolol and diazepam

Summary The cerebrovascular consequences of the gentle restraint commonly used for the measurement of local cerebral blood flow (LCBF) in conscious rats has been tested by using two drugs, propranolol and diazepam. Propranolol induced small LCBF decreases in 7 structures suggesting that the cerebral circulation was partially controlled by the activation of intra or extracerebral aminergic pathways in this protocol. Sedative doses of diazepam reduced LCBF in most of the structures but anxiolytic doses increased it in 4 structures. This effect may be due to a regionally differentiated modification of activity in the brain due to the selective inhibition of limbic structures by diazepam. Since propranolol and diazepam induced only small changes, the LCBF of gently restrained rats appeared to be minimally affected by the stressful situation imposed by the protocol.     

Separate detectors for simple and complex grating patterns?

Grating having two sinusoidal components show a periodic variation in contrast which is visible as a "beat" pattern. The spatial frequency of the beat is the difference between the frequencies of the two components. Thresholds for a number of detection and discrimination tasks were measured using beat patterns of 1 c/deg (with components of 9 and 10 c/deg), and gratings of 1 and 10 c/deg. Temporal modulation at 6 Hz lowered detection thresholds for 1 c/deg gratings, but not for beats or 10 c/deg gratings. The effect of contrast on the range of temporal frequencies over which direction of movement can be discriminated differs for the three types of pattern: beats resemble neither low nor high spatial frequency gratings. Low and (for 2 of 3 observers) high spatial frequency gratings, but not beat patterns, are susceptible to a movement after effect induced by a low spatial-frequency grating. Beat patterns induce little or no movement after effect. We conclude that beat patterns are not detected by the same mechanisms that detect simple gratings.     

Afterimages of sinusoidal, square-wave and compound gratings

Negative afterimages were observed after steady fixation of sinusoidal gratings at low spatial frequencies, and quantified using contrast-matching and cancellation methods. Afterimage contrast increased as a power function of "exposure", defined as the product of inspection contrast and inspection duration. A single function, linear on a log-log plot, describes the afterimages of gratings at different spatial frequencies, contrasts and durations. The matching method yielded a lower slope (about 0.42) than the cancellation method (0.62), probably because contrast adaptation attenuates perceived afterimage contrast in the first method, but not the second. Square-wave gratings, and those containing two or three harmonic components gave much weaker afterimages (assessed by contrast-matching) than sine-waves did. Contrast adaptation may again be responsible. Hemi-field asymmetries in contrast perception were noted. The contrast of real gratings and afterimages was nearly additive, especially at lower exposures, but the results cannot distinguish between linear filter and gain control models of "local adaptation".     

Early-rectal Cancer Treatment: A Decision-tree Making Based on Systematic Review and Meta-analysis

Local excision (LE) has arisen as an alternative to total mesorectal excision for the treatment of early rectal cancer. Despite a decreased morbidity, there are still concerns about LE outcomes.This systematic-review and meta-analysis design is based on the “PICO” process, aiming to answer to three questions related to LE as primary treatment for early-rectal cancer, the optimal method for LE, and the potential role for completion treatment in high-risk histology tumors and outcomes of salvage surgery.The results revealed that reported overall survival (OS) and disease-specific survival (DSS) were 71%–91.7% and 80%–94% for LE, in contrast to 92.3%–94.3% and 94.4%–97% for radical surgery. Additional analysis of National Database studies revealed lower OS with LE (HR: 1.26; 95%CI, 1.09–1.45) and DSS (HR: 1.19; 95%CI, 1.01–1.41) after LE. Furthermore, patients receiving LE were significantly more prone develop local recurrence (RR: 3.44, 95%CI, 2.50–4.74). Analysis of available transanal surgical platforms was performed, finding no significant differences among them but reduced local recurrence compared to traditional transanal LE (OR:0.24;95%CI, 0.15–0.4). Finally, we found poor survival outcomes for patients undergoing salvage surgery, favoring completion treatment (chemoradiotherapy or surgery) when high-risk histology is present.In conclusion, LE could be considered adequate provided a full-thickness specimen can be achieved that the patient is informed about risk for potential requirement of completion treatment. Early-rectal cancer cases should be discussed in a multidisciplinary team, and patient's preferences must be considered in the decision-making process.     

Long-term survivors following autologous haematopoetic stem cell transplantation have significant defects in their humoral immunity against vaccine preventable diseases,years on from transplant

Current international guidelines recommend routinely vaccinating haematopoetic stem cell transplant (HSCT) recipients. Despite significant infection-related mortality following autologous HSCT, routine vaccination programmes (RVP) completion is poor. For recovered HSCT recipients, it is uncertain whether catch-up vaccination remains worthwhile years later.To determine potential susceptibility to vaccine preventable infections, we measured antibody titres in 56 patients, a median of 7 years (range 0–29) following autologous HSCT, who had not completed RVP. We found that almost all participants had inadequate titres against diphtheria (98.2%) and pneumococcal infection (100%), and a significant proportion had inadequate titres against measles (34.5%). Of those subsequently vaccinated according to available guidelines, many mounted adequate serological responses.These data suggest a pragmatic catch-up approach for autologous HSCT recipients who have not completed RVP is advisable, with universal vaccination against some pathogens (e.g. Streptococcus pneumoniae and diphtheria) and serologically-guided approaches for others (e.g. measles and varicella zoster virus).     

保留下颌骨舌癌联合根治术后复发部位及其因素的分析

作者报道６８例行保留下颌骨舌癌联合根治术病例,其中术后复发２３例,复发率为３３．８％。在这２３例中,其复发部位为：局部复发１５例,对侧颈淋巴结转移７例,肝转移１例。这表明术后局部复发病例数最多,占６５．２％（１５／２３）。此类复发病例再无拯救手术机会、预后极差。本文还着重分析了术后复发因素。认为术后复发与肿瘤原发部位及原发灶病变范围有关。     

Improved survival in young women with breast cancer

Background: Young age has been hypothesized to be an adverse prognostic factor for women with breast cancer. This association, based on historical data, may not reflect recent advances in breast cancer management. Methods: A retrospective study was conducted of all women age 30 or younger who underwent definitive operation at our institution for primary operable breast carcinoma during one of two consecutive 20-year periods (1950–1969 or 1970–1989). All cancers were restaged according to current staging criteria. Actuarial survival and recurrence-free survival rates from the two patient eras were compared with each other and with published statistics for older breast cancer patients. Results: Eligibility criteria were met by 81 women from the 1950–1969 era and 146 women from the 1970–1989 era. Histologic diagnoses, tumor sizes, incidence of axillary nodal metastases, number of positive nodes, and American Joint Committee on Cancer stage at presentation were similarly distributed in the two eras. Despite these similarities, improved survival (p=0.009) was observed in the later era. Local recurrences were also more common (p<0.05) in the later era in association with less extensive resections. These local recurrences had an adverse impact on recurrence-free survival in the later era, but no concomitant decrease in overall survival was observed. Node-positive patients who received chemotherapy demonstrated a trend toward improved survival (p=0.06) compared with node-positive patients who did not. Survival for patients in the later era was similar to that for older women as reported in other published series. Conclusions: The stage of presentation of breast cancer in women 30 years or younger appears unchanged from prior decades, but survival has improved in association with the use of less extensive surgical resections and the introduction of cytotoxic chemotherapy. With current treatment, primary operable breast cancer in young women appears to have a similar prognosis to breast cancer in older women.Results of this study were presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994, and was judged Best Clinical Paper in the Resident/Fellow Essay Contest.     

江苏省正常人群破伤风抗体水平监测

用间接血凝法检测了江苏省862名0～39岁正常人的破伤风抗体,结果显示：破伤风抗体阳性率为77．26％,平均抗毒素为0．0543IU／ml,比1985年有极显著提高。不同年龄组中以2～4岁平均抗毒素和保护率最高,3月龄最低,18岁以后随着年龄增长抗体阳性率下降到75％．育龄期妇女抗体阳性率为75．49％,21～30岁生育高峰年龄抗体阳性率仅为69．67％．江苏省南北不同地区人群破伤风免疫水平的差异有极显著的统计学意义,不同性别间差异无显著的统计学意义．     

育龄期妇女不同剂次破伤风类毒素免疫的效果观察

为观察不同剂次破伤风类毒素（ＴＴ）的免疫效果,对我省郑州市金水区、密县、辉县和三门峡市８５８名育龄期妇女分别进行１．２、３剂次免疫。结果显示,经１、２、３剂次ＴＴ免疫后,抗毒素均可达到较高水平,分别为０．２５ＩＵ／ｍｌ、１．００３ＩＵ／ｍｌ、１．０９３ＩＵ／ｍｌ,保护率分别达到８４１％、９６．５％、９１１％．