[125I]CGP 42112 reveals a non-angiotensin II binding site in 1-methyl-4-phenylpyridine (MPP+)-induced brain injury

Summary 1. Intracerebral injection of the oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridine (MPP⁺), into the substantia nigra of adult rats resulted in a lesion at the injection site.2. Using autoradiography, we localized specific [¹²⁵]CGP 42112 binding that was not recognized by angiostensin II or angiotensin II AT₁ or AT₂ receptorselective ligands.3. Our results suggest that [¹²⁵I]CGP 42112 may be binding to activated microglia that appear at the lesion site.     

Enhanced Phosphodiestric Breakdown of Phosphatidylinositol Bisphosphate After Experimental Brain Injury

Abstract: Regional levels of lactate and inositol 1,4,5-trisphosphate (IP₃), a cellular second messenger of the excitatory neurotransmitter system, were measured after lateral fluid percussion (FP) brain injury in rats. At 5 min postinjury, tissue lactate concentrations were significantly elevated in the cortices and hippocampi of both the ipsilateral and contralateral hemispheres. By 20 min postinjury, lactate concentrations were elevated only in the cortices and hippocampus of the ipsilateral hemisphere. Whereas the IP₃ concentrations were elevated in the hippocampi of the ipsilateral and contralateral hemisphere and in the cortex of ipsilateral hemisphere at 5 min postinjury, no elevation in these sites was found at 20 min postinjury. Histologic analysis revealed neuronal damage in the cortex and CA3 regions of hippocampus ipsilateral to the injury at 24 h postinjury. The present results suggest activation of the phosphoinositide signal transduction pathway at the onset of injury and of a possible requirement of early persistent metabolic dysfunction (>20 min) such as the lactate accumulation in the delayed neuronal damage.     

Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer

We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p<0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a paragraph of methods.The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the high-risk patients for LC.     

Magnesium-deficiency potentiates free radical production associated with postischemic injury to rat hearts: Vitamin E affords protection

Preexisting magnesium deficiency may alter the susceptibility of rat hearts to postischemic oxidative injury (free radicals). This was examined in rats maintained for 3 weeks on a magnesium-deficient (Mg-D) diet with or without concurrent vitamin E treatment (1.2 mg/day, SC). Magnesium-sufficient (Mg-S) rats received the same diet supplemented with 100 mmol Mg/kg feed. Following sacrifice, isolated working hearts were subjected to 30-, 40-, or 60-min global ischemia and 30-min reperfusion. Postischemic production of free radicals was monitored using electron spin resonance (ESR) spectroscopy and spin trapping with -phenyl-N-tert butylnitrone (PBN, 3 mM final); preischemic and postischemic effluent samples were collected and then extracted with toluene. PBN/alkoxyl adduct(s) (PBN/RO·; _H = 1.93 G,_N = 13.63 G) were the dominant signals detected in untreated Mg-S and Mg-D postischemic hearts, with comparably higher signal intensities observed for the Mg-D group following any ischemic duration. Time courses of postischemic PBN/RO· detection were biphasic for both groups (maxima: 2–4 and 8.5–12.5 min), and linear relationships between the extent of PBN/RO· production and the severity of both mechanical dysfunction and tissue injury were determined. Following each duration of ischemia, Mg-D hearts displayed greater levels of total PBN adduct production (1.7 –2.0 times higher) and lower recovery of cardiac function (42–48% less) than Mg-S hearts. Pretreating Mg-D rats with vitamin E prior to imposing 40-min ischemia/reperfusion, led to a 49% reduction in total PBN/RO· production, a 55% lower LDH release and a 2.2-fold improvement in functional recovery, compared to untreated Mg-D hearts. These data suggest that magnesium deficiency predisposes postischemic hearts to enhanced oxidative injury and functional loss, and that antioxidants may offer significant protection against pro-oxidant influence(s) of magnesium deficiency.     

Effects of sulfur dioxide and ozone on intact leaves and isolated mesophyll cells of groundnut plants (Arachis hypogaea L.)

Difference between effects of sulfur dioxide (SO₂) and ozone (O₃) on groundnut plants (Arachis hypogaea L.) was studied by use of an exposure system of enzymatically-isolated mesophyll cells. SO₂ inhibited photosynthesis of intact groundnut leaves but induced no visible injury on leaves. SO₂ also inhibited photosynthesis of isolated mesophyll cells but did not kill the cells, suggesting that SO₂ inhibits photosynthesis by attacking rather specifically the photosynthetic apparatus in chloroplasts. O₃ inhibited photosynthesis of intact leaves and at the same time induced visible injury corresponding to the extent of photosynthesis inhibition. O₃ also inhibited photosynthesis of isolated mesophyll cells and killed the cells to the extent corresponding to photosynthesis inhibition, suggesting that O₃ inhibits photosynthesis not directly by attacking the photosynthetic apparatus but indirectly by killing cells. Since the response of intact leaves to each pollutant resembled that of isolated mesophyll cells, the difference between responses of intact leaves to both pollutants may considerably reflect that of mesophyll cells.     

Fibrolast growth factors in the nervous system

Fibroblast growth factors (FGFs) exhibit widespread mitogenic and neurotrophic activities. Nine members of the family are currently known, and FGF-1 and FGF-2 are present in relatively high levels in CNS. FGF-1 is expressed by a subset of neuronal populations, while FGF-2 is expressed by astrocytes. FGF-1 and FGF-2 lack signal peptides and appear to be present mainly in inracellular compartmens. This suggests that the factors may act as initiators of a repair response after injury. Support for this notion comes from observations that FGF-1 and FGF-2 levels are low during critical phases of development, but high in the adult CNS. A family of transmembrane tyrosine kinase receptors (FGFRs) mediates the effects of FGFs. Four different genes coding for FGF receptors are currently known, three of which are expressed in cell type-specific patterns in the CNS The main receptor variants present in this tissue, however, can by themselves not distinguish between FGF-1 and FGF-2. Additional selectivity may be established by interaction of the FGFs and their receptors with select heparan proteoglycans (HSPGs). Therefore, the precise physiological role of FGFs is determined by the combination of cell type-specific patterns of expression of FGFs, FGFRs and HSPGs together with the mechanisms that regulate the extracellular availability of FGFs. 1994 John Wiley & Sons, Inc.     

内毒素致大鼠肺损伤时肺组织β受体的变化与膜磷脂代谢的关系

采用放射性配基结合分析法,现察内毒大致大鼠急性肺损伤时肺β－肾上腺素能受体（β－ＡＲ）的变化。分别用荧光偏振法和高效液相色谱测定肺组织细胞膜脂流动性和磷脂含量。结果显示：（１）静脉注射内毒素后４ｈ,大鼠肺β－ＡＲ的最大结合容量明显降低,较对照组减少４７％;（２）内毒素组肺膜脂流动性和磷脂含量均明显降低,同时伴有肺组织磷脂酶Ａ２（ＰＬＡ２）活性升高。提示：（１）β－ＡＲ下调导致其介导的功能减弱,在内毒素诱导的大鼠急性肺损伤发病机理中起一定作用;（２）ＰＬＡ２激活是膜磷脂减少的重要原因,后者可导致膜脂流动性降低,结果引起β－ＡＲ的侧向扩散和旋转运劝减弱,从而减少β－ＡＲ与配基结合的机率,出现β－ＡＫ下调。     

人肝刺激因子对大鼠实验性慢性肝损伤的保护作用

从健康孕妇水囊引产４─６个月龄的胎儿取肝,采用ＬａＢｒｅｃｑｕｅ方法提取人肝刺激因子（ｈＨＳＳ）。经３Ｈ－胸腺嘧啶核苷参入肝ＤＮＡ法测定其生物活性。表明此ｈＨＳＳ可刺激肝细胞ＤＮＡ合成。采用皮下注射ＣＣｌ４和饮用１０％乙醇来制备慢性肝损伤动物模型,观察了ｈＨＳＳ的保护肝脏作用。结果表明：ｈＨＳＳ可使ＣＣｌ４－乙醇所致慢性肝损伤大鼠的死亡率、血清谷丙转氨酶水平、肝组织中羟脯氨酸含量的升高以及肝组织中丙二醛的含量降低。肝组织切片表明：ｈＨＳＳ能减轻肝组织的损伤程度,促进肝细胞再生,并能明显防止肝纤维化的形成和发展。可见,ｈＨＳＳ对ＣＣｌ４－乙醇所致的慢性肝损伤大鼠有明显的保护作用,其机制可能与促进肝细胞再生及抑制肝细胞膜的脂质过氧化有关。     

重组BCG口服免疫诱导的细胞和体液免疫应答

重组ＢＣＧ口服免疫诱导的细胞和体液免疫应答最近研究证明,外源基因能在牛分枝杆菌ＢＣＧ中表达,用这些重组分枝杆菌免疫小鼠可诱导抗外来蛋白的细胞和抗体免疫应答。近年来的许多研究也证实了肠道和呼吸道粘膜淋巴系统在防御感染方面的贡献,因此,迫切需要能够刺激粘...     

Characteristics of two cell lines derived from a histologically undifferentiated bronchial carcinoma expressing neuroendocrine markers

Summary This study investigates the characteristics of two human cell lines—1PT and 1PT VARIANT A—both derived from the same histologically undifferentiated, neuroendocrine positive, non-small cell lung carcinoma (NSCLC) and capable of growth in unsupplemented serum-free minimum essential medium. In stationary culture, the cells of both lines grew both attached to a plastic substratum and in suspension; the 1PT VARIANT A line formed three-dimensional clusters of loosely adherent cells. The cell lines differed in their DNA content, the 1PT having 1.44 times and the 1PT VARIANT A having 2.39 times the normal human diploid DNA content. Chromosome counts supported this observation, the ploidy of the 1PT and VARIANT A lines being 1.11 and 1.64, respectively. On transmission electron microscopy the cells of both lines had dense core granules and immature desmosomes, whereas only the 1PT VARIANT A line had mucin granules. Both lines formed, in nude mice, tumors that, like the original tumor from which they were derived, were histologically undifferentiated and showed local invasion. The original tumor and both lines had demonstrable neuroendocrine markers. Cytokeratins were apparent in the tumor but not the cell lines, and neurofilaments were present in the cell lines only. Staining for epithelial membrane antigen, neural cell adhesion molecule, and desmoplakin differentiated between the two lines. These lines provide a useful model for the investigation of the biology of the neuroendocrine positive subgroup of NSCLC, which is clinically important because of the possible responsiveness of these tumors to chemotherapy.