Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses

Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development.     

Effect of fatty acid anilides on immune responses of Swiss mice.

The possible relationship between fatty acid anilides and the toxic oil syndrome (TOS) which appeared in Spain in 1981 has been debated during recent years. These anilides have been detected as anomalous compound in toxic oils analysed. After treatment with one daily dose of 50 mg/kg of oleilanilide (88.86% pure) for 5 days, animals showed a tendency towards progressive loss of body weight and a significant increase in serum concentration of immunoglobulins. The percentage of suppressor T cells in spleen diminished significantly compared with the control group. Consequently, an increase in the helper T cells/suppressor T cells was also observed. The production of IgM and IgG in culture was significantly higher than in controls and no differences were seen in IgA synthesis. The functional studies of generation of specific IgM, IgA and IgG suppressor cells at variable doses of concanavalin A (Con A) showed paradoxical behaviour of suppressor T cells generated by low doses of Con A. A similar change occurred at higher doses of Con A. These results suggest that low-dose treatment with oleilanilides induces an alteration in the immune response in Swiss mice.     

Inappropriate peripheral blood lymphocyte responses to herpes viruses in patients with behçet's syndrome

Specific antibody production and the proliferative response of peripheral blood lymphocytes (PBLs) to a variety of viruses, including herpes simplex virus-type-1 (HSV-1) and varicella zoster (VZ), were studied in 7 patients with Behçet's syndrome. None of the patients produced an antibody response against HSV-1 or VZ. Furthermore, none of the patients showed a proliferative response to VZ, and three of them also failed to mount a response to HSV-I. These results suggest that the PBLs of patients with Behçet's syndrome make an inappropriately poor antibody and proliferative response when stimulated by HSV-1 and VZ.     

Work performance breathing normoxic nitrogen or helium gas mixtures

Summary Twelve subjects completed a progressive treadmill test to maximal aerobic capacity while breathing air or a 79% helium — 21% oxygen gas mixture (HeO₂). Metabolic and thermoregulatory responses to work while breathing the two mixtures were compared at rest, 30–40%, 60–70%, and 85–95% of maximal performance, and at maximal effort. Ventilation, ventilatory equivalent, and respiratory rates were increased and oxygen uptakes decreased by breathing HeO₂ when the level of work exceeded 85–95% of maximum. Heat loss through the respiratory tract was greater breathing HeO₂. The reduction in maximal oxygen uptake is probably due to a reduction in the oxygen cost of breathing a less dense gas. It was not related to a lower body temperature and probably not to O₂ transport or circulatory limitation. HeO₂ breathing had no effect on maximal mechanical work capacity.The nature and purpose of the study and the risks involved were explained verbally and given on a written form to each subject prior to his or her voluntary consent to participate. The protocol and procedures for this study have been approved by the Committee on Activities Involving Human Subjects, of the University of California, Santa Barbara, California, USA     

Psychophysiological Predictors of Attentional Dysfunction in Children with Congenital Heart Defects

Cardiac responses to non-signal stimuli and to signal stimuli in a vigilance task were examined in children born with congenital heart defects (CHD), and in normal and attention deficit disordered (ADD) subjects. Overall task performance was lower in subjects with heart defects and in the ADD group. Cardiac measures revealed that normal children displayed significantly larger heart rate deceleration to the target stimuli than did either of the clinical groups. Moreover, although no group differences were observed in the cardiac response to non-signal auditory stimuli, exaggerated heart rate deceleration was observed to vibrotactile stimuli in both the clinical groups. Regression analyses revealed that the magnitude of the cardiac response to somatosensory stimuli was predictive of task performance (both within and between subject groups), with larger responses associated with higher error rates and lower perceptual sensitivity. Results were suggestive of a predictive relationship between somatosensory reactivity and neuropsychological maturation.     

社交性应激反应问卷中文版在大学生中应用的信效度初步评价

目的：建立社交性应激反应问卷（RSQ-SSV）中文版，并分析其信、效度。方法：按量表翻译程序将RSQ—SSV翻译成中文，整群分层选取409名大学生进行RSQ—SSV中文版的测量。随机抽取90名学生于初评后一个月进行重测，并与美国样本进行比较。结果：RSQ-SSV中文版整个问卷的Cronbach α系数为0．88，各因子仅系数在0．73～0．81之间；重测信度为0．70；全量表的条目间平均相关系数为0．11，5因子的条目间平均相关系数在0．19～0．29之间，因子间相关系数在0．12～0．76之间；条目对因子负荷系数在0．38—0．86之间，复相关系数在0．14—0．74之间；验证性因子分析的指标：IFI为0．93，CFI为0．93，TLI为0．92，RMSEA为0．06。中国大学生样本的不随意的逃避反应因子得分高于美国大学生样本[（0．97±0．41）vs．（0．91±0．48），P=0．002]，而初级亲近控制应对反应、次级亲近控制应对反应、不随意的亲近反应得分均低于美国大学生样本[（1．75±0．49）vs．（2．12±0．50）、（1．51±0．43）vs．（1．80±0．48）、（1．17±0．44）vs．（1．36±0．56），均P〈0．001]。结论：RSQ-SSV中文版具有良好的信、效度，可以试用于我国大学生社交性应激反应的测评。     

酮替酚对鸡蛋过敏特应性皮炎患儿淋巴细胞增殖反应的抑制作用

作者探讨了鸡蛋过敏特应性皮炎(AD)患儿外周血单个核细胞(PBMCs)对卵白蛋白(OA)刺激的增殖反应并观察了酮替酚(KF)对此反应的影响.结果提示AD患儿的PBMCs增殖反应显著高于健康儿童;KF可剂量依赖性地抑制鸡蛋过敏AD患儿PBMCs对OA刺激的增殖反应,且这一效应可通过KF抑制T细胞的作用而得以实现.KF对植物血凝素(PHA)和破伤风类毒素(TT)诱导的PBMCs增殖反应无抑制作用.这说明KF只抑制食物过敏AD患者PBMCs对食物抗原的特异性增殖反应.     

Electrodermal Orienting Responses to Onset and Offset of Auditory Stimulation under Nonsignal Conditions

It has previously been reported that the orienting reflex (OR) to the onset of a stimulus habituates more slowly than the OR to stimulus offset. In this paper, we attempted to account for this in terms of differences between the ON condition (whose presentation elicits the onset OR) and the OFF condition (whose “presentation” elicits the offset OR). Because the typical habituation paradigm begins with a period of adaptation to the OFF (stimulus absent) condition, the relative novelty of the ON condition is enhanced. This bias would contribute to the advantage of onset ORs over offset responses. This hypothesis was evaluated by comparing skin conductance responses (SCRs) to onset and offset of a 600 Hz tone in a group adapted in the presence of that tone (Tone Adaptation, TA) vs one adapted in its absence (Silent Adaptation, SA). The results supported our hypothesis; onset ORs habituated significantly more slowly than offset ORs in Group SA, but not in Group TA.     

Loads applied tangential to a fingertip during an object restraint task can trigger short-latency as well as long-latency EMG responses in hand muscles

Electrical stimulation of the digital nerves can cause short- and long-latency increases in electromyographic activity (EMG) of the hand muscles, but mechanical stimulation of primarily tactile afferents in the digits generally evokes only a long-latency increase in EMG. To examine whether such stimuli can elicit short-latency reflex responses, we recorded EMG over the first dorsal interosseous muscle when subjects (n=13) used the tip of the right index finger to restrain a horizontally oriented plate from moving when very brisk tangential forces were applied in the distal direction. The plate was subjected to ramp-and-hold pulling loads at two intensities (a 1-N load applied at 32 N/s or a 2-N load applied at 64 N/s) at times unpredictable to the subjects (mean interval 2 s; trial duration 500 ms). The contact surface of the manipulandum was covered with rayon—a slippery material. For each load, EMG was averaged for 128 consecutive trials with reference to the ramp onset. In all subjects, an automatic increase in grip force was triggered by the loads applied at 32 N/s; the mean onset latency of the EMG response was 59.8±0.9 (mean ± SE) ms. In seven subjects (54%) this long-latency response was preceded by a weak short-latency excitation at 34.6±2.9 ms. With the loads applied at 64 N/s, the long-latency response occurred slightly earlier (58.9±1.7 ms) and, with one exception, all subjects generated a short-latency EMG response (34.9±1.3 ms). Despite the higher background grip force that subjects adopted during the stronger loads (4.9±0.3 N vs 2.5±0.2 N), the incidence of slips was higher—the manipulandum escaped from the grasp in 37±5% of trials with the 64 N/s ramps, but in only 18±4% with the 32-N/s ramps. The deformation of the fingertip caused by the tangential load, rather than incipient or overt slips, triggered the short-latency responses because such responses occurred even when the finger pad was fixed to the manipulandum with double-sided adhesive tape so that no slips occurred.     

Cortico-cortical mediation of short-latency (lemniscal) sensory input to the motor cortex in deeply pentobitone anaesthetized cats

In pentobarbitone-anaesthetized cats, responses were recorded as surface positive potentials in the motor cortex on forelimb and brachium conjunctivum stimulation. In such a preparation, the forelimb nerve responses are mediated via the spino-cervical tract and the dorsal column-lemniscal pathway. Lesions of the sensory cortex (sparing only the depth of the coronary sulcus) abolished or reduced short-latency peripheral responses, in the motor cortex, on both skin and muscle nerve stimulation to less than 10% of control, while brachium conjunctivum responses were unchanged. Lesions of the second somatosensory area alone reduced the motor cortex responses on peripheral nerve stimulation by 10–20%. When the sensory cortex were abolished before the spreading depression reached the recording point, as judged from the brachium conjunctivum response. The depth distribution of positive and negative field potentials, constituting the early componentsof a peripheral response in the motor cortex, closely resembled that of a cortico-cortical response evoked on stimulation in area 3. It differed from that of thalamo-cortical response evoked in brachium conjunctivum stimulation. These data suggest that most, if not all, sensory input through the dorsal column and spino-cervical tract to the motor cortex is mediatd via the sensory cortex.