空肠弯曲菌慢性感染诱致自身免疫反应的机理初探

用空肠弯曲菌CJ—S131株感染昆明种小鼠3个月,观察到:(1)感染鼠血清中,出现高滴度的抗ds—DNA和ss—DNA抗体;(2)Con A诱导的抑制细胞功能降低和TH/Ts细胞比值增加;(3)PFC形成和LPS诱致的淋巴细胞转化作用增强:(4)DTH和Con A及PHA诱致的淋巴细胞转化作用增强。提示,CJ—S131感染小鼠使其T_S细胞功能降低,导致T_H细胞功能偏亢,B细胞功能亢进,这可能与自身免疫反应的产生有关。     

Increased expression of apoptosis-linked gene 2 (ALG2) in the rat brain after temporary focal cerebral ischemia

Calcium is an important mediator of programmed cell death induced by transient cerebral ischemia, and calcium-binding proteins have been implicated in calcium-regulated signal transduction. Apoptosis-linked gene 2 is a calcium-binding protein required for cell death induced by different apoptotic stimuli. By Western blot analysis, we found that apoptosis-linked gene 2 protein was expressed in normal brains, and that expression increased in ischemic brains after 20 or 90 min of transient focal cerebral ischemia. Immunocytochemistry showed increased apoptosis-linked gene 2 protein expression in frontal cortex, a region where neurons underwent ischemic stress but still survived, after 20 or 90 min of focal cerebral ischemia. Apoptosis-linked gene 2 protein was also up-regulated in the ischemic border-zone of parietal cortex 24h after 20 min of focal ischemia, and was remarkably over-expressed in the caudate-putamen and parietal cortex, (where cells are destined to die) 24h after 90 min of ischemia. The expression pattern of apoptosis-linked gene 2 protein was similar to that of deoxyribonucleic acid damage detected by Klenow labeling assay.Our results suggest that apoptosis-linked gene 2 may be involved in the regulation of cell death after transient focal cerebral ischemia.     

Role of O2-sensitive K and Ca channels in the regulation of the pulmonary circulation: Potential role of caveolae and implications for high altitude pulmonary edema

High altitude pulmonary edema (HAPE) is a potentially fatal complication in response to exposure to low O₂ at high altitudes. Hypoxia, by causing pulmonary vasoconstriction, increases pulmonary vascular resistance and pulmonary arterial pressure, both of which are features in the pathogenesis of HAPE. Uneven hypoxic pulmonary vasoconstriction is thought to be responsible for increased capillary pressure and leakage, resulting in edema. O₂-sensitive ion channels are known to play pivotal roles in determining vascular tone in response to hypoxia. K⁺, Ca²⁺ and Na⁺ channels are ubiquitously expressed in both endothelial and smooth muscle cells of the pulmonary microvasculature, subfamilies of which are regulated by local changes in P_O2. Hypoxia reduces activity of voltage-gated K⁺ channels and down-regulates their expression leading to membrane depolarization, Ca²⁺ influx in pulmonary artery smooth muscle cells (by activating voltage-dependent Ca²⁺ channels) and vasoconstriction. Hypoxia up-regulates transient receptor potential channels (TRPC) leading to enhanced Ca²⁺ entry through receptor- and store-operated Ca²⁺ channels. Altered enrichment of ion channels in membrane microdomains, in particular in caveolae, may play a role in excitation–contraction coupling and perhaps in O₂-sensing in the pulmonary circulation and thereby may contribute to the development of HAPE. We review the role of ion channels, in particular those outlined above, in response to low O₂ on vascular tone and pulmonary edema. Advances in the understanding of ion channels involved in the physiological response to hypoxia should lead to a greater understanding of the pathogenesis of HAPE and perhaps in the identification of new therapies.     

DNA prime followed by protein boost enhances neutralization and Th1 type immunity against FMDV

Prime-boost strategy has been exhibited its potency to enhance immune responses, which would be important to the success to develop a vaccine against the foot-and-mouth disease virus (FMDV). An eukaryotic expression construct encoding the FMDV capsid VP1 protein with a recombinant VP1 protein or a commercial FMDV vaccine were tested in the prime-boost strategy in mice and cattle trials. The levels of induced specific antibodies, T cell proliferations, and DTH activities were significantly higher in the prime-boost groups than in those vaccinated with DNA, protein or FMDV vaccine alone. More importantly, the levels of neutralizing antibodies in the former groups were significantly higher than others and could last for at least four months in cattle trials. This study suggests that the prime-boost strategy significantly improves the effective immunity and may provide a longer protection against FMDV infection.     

Locations of spinothalamic tract axons in cervical and thoracic spinal cord white matter in monkeys

The spinothalamic tract (STT) is the primary pathway carrying nociceptive information from the spinal cord to the brain in humans. The aim of this study was to understand better the organization of STT axons within the spinal cord white matter of monkeys. The location of STT axons was determined using method of antidromic activation. Twenty-six lumbar STT cells were isolated. Nineteen were classified as wide dynamic range neurons and seven as high-threshold cells. Fifteen STT neurons were recorded in the deep dorsal horn (DDH) and 11 in superficial dorsal horn (SDH). The axons of 26 STT neurons were located at 73 low-threshold points (<30 microA) within the lateral funiculus from T(9) to C(6). STT neurons in the SDH were activated from 33 low-threshold points, neurons in the DDH from 40 low-threshold points. In lower thoracic segments, SDH neurons were antidromically activated from low-threshold points at the dorsal-ventral level of the denticulate ligament. Neurons in the DDH were activated from points located slightly ventral, within the ventral lateral funiculus. At higher segmental levels, axons from SDH neurons continued in a position dorsal to those of neurons in the DDH. However, axons from neurons in both areas of the gray matter were activated from points located in more ventral positions within the lateral funiculus. Unlike the suggestions in several previous reports, the present findings indicate that STT axons originating in the lumbar cord shift into increasingly ventral positions as they ascend the length of the spinal cord.     

Diet restriction plays an important role in the alterations of heart mitochondrial function following exposure of young rats to chronic hypoxia

Male Wistar rats aged 4 weeks, were subjected to hypobaric hypoxia (barometric pressure 505 hPa, PI,O2 106 hPa) or to diet restriction (reproducing the effect of hypoxia-induced anorexia) for 4 weeks. Each group (control, hypoxic, pair-fed, n = 16), was divided into two sub-groups housed individually in either normal cages or cages with running wheels allowing evaluation of voluntary activity (n = 8 each). The skinned-fibre technique was used to evaluate the functional properties of myofibrillar mitochondria from right and left ventricles in situ. The oxidative fibres from the soleus and diaphragm muscles were also investigated for comparison. Analysis of variance did not detect any significant effect of voluntary running activity. With calorie restriction, the maximal respiratory rate (Vmax) in the presence of 1 mM adenosine 5'-diphosphate (ADP) in myocardial fibres fell significantly (by about 25%) but was unchanged in skeletal myocytes. Following hypoxia, Vmax in myocardial fibres increased by 25% compared with the calorie restricted group and in soleus and diaphragm muscle fibres by about 30% compared with control. In myocardial fibres of control rats, creatine (20 mM) increased the sub-maximal respiratory rate by 80% in the presence of 0.1 mM ADP. Under calorie restriction or hypoxia the stimulatory effect was significantly reduced to 34-56%. This alteration was due to a decrease in the apparent Michaelis-Menten constant (Km) of mitochondrial respiration for ADP evaluated in the absence of creatine, while the Km in presence of creatine 20 mM was unchanged. In conclusion, reduced food intake decreased the oxidative capacity (Vmax) and the apparent Km for ADP of mitochondria in both left and right ventricles. Chronic hypoxia per se was responsible for an increase in the oxidative capacity of all oxidative muscles but did not exert significant effects on the control of respiration by ADP and creatine in myocardium.     

Nonrandomness of D-group chromosomes involved in centric-fusion translocation

Ten members of two families with D/G translocation, three members of a family with D/D translocation, and one patient with non-familial and one with apparently non-familial D/D translocation were examined. The trdnslocation chromosomes were identified by SH-thymidine labeling and autoradio-graphy as 14q21q and 13q14q, respectively. These findings support the hypothesis of nonrandomness of D group chromosomes involved in centric-fusion translocation. The importance of the identification of Dgroup chromosomes involved in centriofusion translocation in relation to genetic counseling is discussed.     

Simulation study of the Hemopump as a cardiac assist device

A dynamic model was developed for a Hemopump that withdraws blood from the left ventricle and discharges it to the aorta through a miniature axial-flow pump. Incorporation of the Hemopump model in a previously established model for the canine circulatory system enabled the effects of the Hemopump on various haemodynamic variables of the circulatory system to be studied, and the benefit of the Hemopump to the failing heart was investigated. In addition, the influence of the physiological status of the right ventricle on the Hemopump performances was examined, and the synchronous and non-synchronous operations of the Hemopump were compared. Results verified that the Hemopump assists the failing heart by increasing the oxygen supply, while reducing the oxygen consumption of the heart through a reduction in the workload of the left ventricle. These beneficial effects were enhanced when the pump's rotation speed was increased. When pump speed was increased from 17000 to 23000 revolutions min⁻¹, the oxygen supply increased 101%, and the oxygen consumption decreased 60%. However, when the pump rotation speed was too high, the inflow to the pump could be impaired and the pump performance could be negatively affected. Predications from the model were in good agreement with the results previously obtained in animal experiments and in vitro measurements.