开发和应用卡车、客车自动变速器方面的经验

制造商、车辆拥有者和驾驶员对传动系统都有自己的评判标准。但与用户相关的高可靠性和较低使用成本是评判的基础。为满足这些目标,特开发出一种高度集成的自动变速器系统。驾驶员采用一双踏板的线控系统,不需离合器踏板。可选择全自动或手动模式。新的变速器系统有10、12和16档变速器等系列。对变速器自身而言,离合器单元、变速器单元和软件等被开发成将其功能和元件集成在一些单独可测试模块中。该系统可与车辆其它系统如EDC、ABS或缓速器系统（称为INTARDER）通过标准的CAN－bus-System(SAE J 1939）转换信息。系统的概念和所采用的解决方法如上。以下讨论其特点和研究结果。     

Effect of Cu2+ on relaxations to the nitrergic neurotransmitter, NO and S-nitrosothiols in the rat gastric fundus

1. The effects of superoxide anion generators before and after treatment with inhibitors of Cu/Zn superoxide dismutase (Cu/Zn SOD) and the effects of thiol-modulating agents were investigated on nitrergic relaxations to electrical stimulation of non-adrenergic non-cholinergic (NANC) nerves of the rat gastric fundus and on relaxations to authentic nitric oxide (NO) and nitroglycerin. 2. The superoxide anion generators, pyrogallol (30 microM) and duroquinone (30-60 microM), significantly inhibited the relaxations to NO (0.03-3 microM) but not nitrergic relaxations to NANC nerve stimulation (0.5-8 Hz) or those to ATP (10 microM). Treatment of the rat gastric fundus with the inhibitors of Cu/Zn SOD, diethyldithiocarbamate (DETC, 1 mM for 2 h) or triethylenetetramine (TETA, 100 microM for 2 h) had no effect on the relaxations to NANC nerve stimulation (1-8 Hz), NO (0.03-3 microM) or on those to ATP (10 microM). 3. After treatment of the rat gastric fundus with DETC (1 mM) but not after treatment with TETA (100 microM), pyrogallol (30 microM) and duroquinone (30-60 microM) significantly inhibited the nitrergic relaxations to electrical stimulation (0.5-8 Hz) and those to NO (0.03-3 microM). This inhibitory effect of pyrogallol and duroquinone was prevented by addition of exogenous SOD (250 units ml-1). Pyrogallol but not duroquinone also inhibited the NO-independent relaxations to ATP (10 microM). 4. The thiol modulators, buthionine sulphoximine (1 mM for 2 h) and ethacrynic acid (30 microM for 2 h), significantly inhibited the relaxations to nitroglycerin (0.03-3 microM) but had no effect on the nitrergic relaxations to electrical stimulation (0.5-8 Hz) or on those to NO (0.03-10 microM) and ATP (10 microM). The thiol modulators, sulphobromophthalein (100 microM for 2 h) and diamide (30-100 microM for 2 h) did not affect the relaxations to nitroglycerin, or those to NANC nerve stimulation and NO. 5. In summary, thiol modulators significantly inhibited the thiol-dependent relaxations to nitroglycerin but not those to NANC nerve stimulation or NO. Relaxations to nitrergic stimulation were decreased by superoxide anion generators only after inhibition of Cu/Zn SOD. These results suggest that the nitrergic NANC neurotransmitter in the rat gastric fundus is not a nitrosothiol but more likely free NO, which is protected from breakdown by tissue SOD.     

Identifying adverse events caused by medical care: degree of physician agreement in a retrospective chart review

Forty critically ill adult patients with severe Gram-negative infection were treated with once-daily amikacin combined with ceftazidime. The mean age was 56.6 +/- 19 years and mean APACHE II score was 22.7 +/- 6.6. Forty percent of patients required mechanical ventilation. The mean creatinine clearance at onset of therapy was 59.4 +/- 28 ml/min. All bacterial isolates were sensitive to amikacin. Fixed doses of amikacin 15 mg/kg, 12 mg/kg, and 8 mg/kg body weight were given once daily to patients with estimated creatinine clearance of > 80 ml/min., 50-80 ml/min., and < 50 ml/min, respectively. Forty-two causative gram-negative bacteria were isolated from 40 patients. The most common bacteria were Pseudomonas aeruginosa (18), and Escherichia coli (10). Overall clinical success and bacteriological eradication occurred in 85% and 87.5% of patients; 78.9% and 79% of patients with hospital-acquired infections; 90.5% and 95.2% of patients with community-acquired infections; and 62.5% and 81.3% of patients requiring mechanical ventilation, respectively. Therapeutic failure was documented in 15% of patients. Death due to infection was scored in two patients. The remaining were all due to persistence of the initial causative bacteria in patients with hospital-acquired infections. Persistence was documented with Ps. aeruginosa (2), Serratia spp. (1), and Acinetobacter spp. (1). Overall mortality occurred in 22.5% patients. Death unrelated to infection occurred in 7 patients. There was no clinical evidence of ototoxicity in any of our patients, however, nephrotoxicity was documented in 5%. In conclusion, once-daily amikacin combined with ceftazidime is practical, efficacious and probably safe in critically ill infected patients.     

Characterization of the binding properties of protein LG, an immunoglobulin-binding hybrid protein

Protein LG is a 50-kDa hybrid molecule containing four Ig-light-chain-binding domains from protein L of Peptostreptococcus magnus and two IgG-Fe-binding repeats from streptococcal protein G. Here we analyse the binding of protein LG to Ig from several mammalian species. Protein LG was shown to bind human IgG of all subclasses and other Ig classes that carry kappa chains. The binding to human IgG was only marginally influenced by changes in temperature (4-37 degrees C) or salt concentration (0-1.6 M), and was stable over a wide pH range (pH 4-10). Protein LG bound to Ig from 11 of 12 mammalian species, including those of rabbit, mouse and rat. The affinity constants obtained for the interactions between protein LG and polyclonal IgG from rabbit (4.0 x 10(9) M-1), mouse (1.7 x 10(9) M-1) and rat (1.3 x 10(9) M-1) were similar to the value previously reported for the interaction between the hybrid protein and human polyclonal IgG (5.9 x 10(9) M-1). The interaction between protein LG and a mouse IgG mAb was not influenced by the presence of the specific protein antigen, nor was the binding of this antibody to its ligand affected by protein LG. Inhibition experiments demonstrated that the Ig-binding site of one of the fusion partners retained its ligand-binding capacity when the other component was occupied. Protein LG selectively absorbed 85-90% of the total Ig present in human and rabbit sera and 75-80% of the Ig in sera from mouse and rat. Human serum depleted of C1q, factor D and properdin and preabsorbed by protein LG could be used as a source for other complement factors. These data demonstrate that protein LG is a very versatile Ig-binding protein.     

Purification and characterization of a soluble form of mammalian adenylyl cyclase

An engineered, soluble form of mammalian adenylyl cyclase has been expressed in Escherichia coli and purified by three chromatographic steps. The enzyme utilizes one molecule of ATP to synthesize one molecule of cyclic AMP and pyrophosphate at a maximal specific activity of 12.8 micromol/min/mg, corresponding to a turnover number of 720 min-1. Although devoid of membrane spans, the enzyme displays all of the regulatory properties that are common to mammalian adenylyl cyclases. It is activated synergistically by Gsalpha and forskolin and is inhibited by adenosine (P-site) analogs with kinetic patterns that are identical to those displayed by the native enzymes. The purified enzyme is also inhibited directly by the G protein betagamma subunit complex. After adenovirus-mediated expression in adenylyl cyclase-deficient HC-1 cells, the enzyme can be stimulated synergistically by Gs-coupled receptors and forskolin.     

Influence of dietary fats upon systolic blood pressure in the rat

Studies were performed to determine whether feeding diets with differing fatty acid content and composition had an influence on systolic blood pressure in the rat. Weanling male rats were fed standard laboratory chow (2.9% fat in total), or synthetic diets (10% fat in total) containing fish oil, butter, coconut oil or corn oil, for 5 weeks. Coconut oil and butter diets were rich in saturated fatty acids, whilst fish oil and corn oil were rich in the n-3 and n-6 unsaturated fatty acids respectively. Systolic blood pressure was measured using an indirect tail-cuff method at the end of the feeding period, and compared to a group of weanling rats. Feeding the different diets did not alter the growth of the rats, so all animals were of similar weights at the time of blood pressure determination. Control (chow fed) animals, at nine weeks of age, had higher systolic blood pressures than the weanling, baseline control group. Fish oil fed rats had similar pressures to the chow fed rats. Corn oil fed rats had significantly lower systolic pressures than the controls. The rats led the diets rich in saturated fatty acids (butter and coconut oil) had significantly higher blood pressures than all other groups. Systolic blood pressure was found to be significantly related to the dietary intakes of saturated and unsaturated fatty acids. The dietary intake of linoleic acid was significantly higher in corn oil fed rats than in other groups. Systolic blood pressure was inversely related to linoleic acid intake. Feeding a diet rich in saturated fatty acids significantly increases blood pressure in the rat. A high intake of n-6 fatty acids, and in particular linoleic acid, appears to have a hypotensive effect. Prenatal exposure of the rats to a maternal low protein diet, abolished the hypertensive effects of the coconut oil diet and the hypotensive effect of the corn oil diet upon young adult females. The intrauterine environment may, therefore, be an important determinant of the effects of these fatty acids on blood pressure in later life.     

Collision tumors of the adrenal gland: demonstration and characterization at MR imaging

PURPOSE: To evaluate the magnetic resonance (MR) imaging findings in collision tumors of the adrenal gland. MATERIALS AND METHODS: MR images obtained in 104 patients with a known primary malignant tumor and an adrenal mass were reviewed to find adrenal glands that contained two contiguous but histologically distinct masses. The findings in such cases were correlated with histopathologic findings. RESULTS: In two (2%) cases, both MR and histopathologic findings showed a mass within the adrenal gland that consisted of contiguous adrenal adenoma and metastasis, which represented a collision tumor. The adenomatous component in each tumor showed a (quantitative) decrease in signal intensity relative to that of the liver (79% and 61%) on opposed-phase images, whereas the metastatic component showed an increase in signal intensity (50% and 15%). Similarly, the adrenal lesion-to-spleen signal intensity ratio on opposed-phase images was lower for the adenomatous component in each (0.39 and 0.43) than for the metastatic component (1.17 and 0.90). CONCLUSION: MR imaging can demonstrate and enable characterization of the separate components of collision tumors within the adrenal gland. These findings can be crucial in planning and guiding subsequent percutaneous needle biopsy and patient care.     

The presence of calbindin in rat cortical neurons protects in vitro from oxydative stress

Free radicals are highly reactive chemicals containing an unpaired electron and are normally produced by the cellular metabolism. The oxydative stress is defined as a lack of balance between the production of free radicals and the activity of antioxydant metabolites. It induces cellular damages to lipids, proteins and membranes. Abnormal calcium metabolism can be a consequence of oxydative stress leading to increased intracellular concentrations. Calbindin D28K is a calcium binding protein which could have a neuroprotective action against various cellular insults. In this study rat cortical cell cultures were exposed during various times and at different concentrations to the couple Xanthine/Xanthine oxydase (XA/XO), which produces the superoxyde radical O2-.. Neuronal survival revealed that XA/XO is toxic for cortical cell cultures. The Calbindin D28K immunocytochemical study shows that the percentages of Calbindin positive cells are greater in surviving neurons following the XA/XO exposure compared to controls. There is a time-dependent and a dose-dependent relation between the number of surviving neurons and the percentage of Calbindin positive neurons. These results suggest that the presence of cytosolic neuronal Calbindin D28k is associated with a greater resistance to oxydative stress.     

Multiple SH3 domain interactions regulate NADPH oxidase assembly in whole cells

Src homology 3 (SH3) domains mediate specific protein-protein interactions crucial for signal transduction and protein subcellular localization. Upon phagocyte stimulation, two SH3 domain-containing cytosolic components of the NADPH oxidase, p47phox and p67phox, are recruited to the membrane where they interact with flavocytochrome b558 to form an activated microbicidal oxidase. Deletion analysis of p47phox and p67phox in transfected K562 cells demonstrated multiple SH3-mediated interactions between p47phox and the transmembrane flavocytochrome b558 and also between the cytosolic components themselves. The core region of p47phox (residues 151-284), spanning both SH3 domains, was required for flavocytochrome-dependent translocation and oxidase activity in whole cells. Furthermore, translocation of p67phox occurred through interactions of its N-terminal domain (residues 1-246) with p47phox SH3 domains. Both of these interactions were promoted by PMA activation of cells and were influenced by the presence of other domains in both cytosolic factors. Deletion analysis also revealed a third SH3 domain-mediated interaction involving the C-termini of both cytosolic factors, which also promoted p67phox membrane translocation. These data provide evidence for a central role for p47phox in regulation of oxidase assembly through several SH3 domain interactions.