Ⅰ期非小细胞肺癌淋巴结微转移规律的研究

目的探讨几个问题：（1）Ⅰ期非小细胞肺癌淋巴结微转移比率；（2）淋巴结微转移与肿瘤大小、病理类型、细胞分化程度、部位、分型、分期进行Logstic回归分析，确定影响微转移的主要因素；（3）探讨微转移的方式、顺序。方法对91例非小细胞肺癌清扫的肺门和隆突下淋巴结进行MCK（AEI／AE3）免疫组化标志检测微转移的存在。另外收集45例肺部良性病变手术时切除的肺门淋巴结45枚和Ⅱ期、Ⅲ期肺癌常规病理检查阳性的肺门淋巴结45枚进行MCK（AEI／AE3）免疫组化（SP法）标志，分别作为阴性和阳性对照。结果45例肺部良性病变手术时切除的肺门淋巴结45枚进行MCK（AEI／AE3）免疫组化标志均为阴性；Ⅱ期和Ⅲ期常规病理检查阳性的肺门淋巴结45枚进行MCK（AEI／AE3）免疫组化标志均为阳性。91例Ⅰ期非小细胞肺癌总的微转移率为49％（45／91）。结论Ⅰ期非小细胞肺癌淋巴结中存在微转移；Ⅰb期非小细胞肺癌微转移率明显高于Ⅰa期；有必要对Ⅰb期非小细胞肺癌进行术后化疗；肿瘤分期和分化程度是影响淋巴结微转移的主要因素；淋巴结微转移遵循肺门到纵隔的途径；腺癌存在跳跃式微转移。     

A phenytoin-sensitive cationic current participates in generating the afterdepolarization and burst afterdischarge in rat neocortical pyramidal cells

We report here on the ionic mechanisms underlying the depolarizing afterpotential (DAP) in neocortical pyramidal cells, with special interest in those underlying the burst afterdischarge. Injections of short depolarizing current pulses under whole-cell current clamp with a CsCl-based internal medium generated, in most pyramidal cells, a single action potential with a plateau phase (plateau-AP), followed by a slowly decaying DAP both in the absence and presence of TTX. Under voltage-clamp, the same cells displayed a slow tail current (tail-I) at the offset of depolarization. When intracellular free Ca²⁺ was chelated with 10 mm BAPTA or when extracellular Ca²⁺ was replaced with equimolar Ba²⁺, neither the slow DAP nor the slow tail-I was observed. Extracellular application of Co²⁺ or Cd²⁺ reduced Ca²⁺ currents and the slow tail-I. Cation substitution experiments revealed that the channel generating the slow tail-I was permeable to K⁺ and Cs⁺ more than to Na⁺ (P_K≈P_Cs > P_Na > P_NMDG≈P_TEA). The cationic slow tail-I was not reduced by applying antagonists of the metabotropic glutamate receptor (MCPG, 1 mm ) and the muscarinic receptor (atropine, 1–10 μm ). Thus, the slow DAP was produced by activation of the cationic channel whose gating is solely dependent on [Ca²⁺]_i. An increase in [K⁺]_o from 3 to 6 or 9 mm enhanced the slow DAP, and resulted in a generation of burst afterdischarges. An anticonvulsant, phenytoin (PT; 1–10 μm ) suppressed the slow DAP while enhancing the plateau-AP in the presence of TTX, most likely by blocking the cationic channel.     

INVOLVEMENT OF PHOSPHOPROTEIN PHOSPHATASE 1 IN COLLAGEN-PLATELET INTERACTION

The binding of type I collagen to its receptor initiates platelet aggregation, but the relationship of the receptor to other signal transduction components is not yet established. Correlation of platelet aggregation and anti-type I collagen receptor antibody immunoprecipitation of type I collagen treated [³²PO4]-labeled platelets showed that there are two phosphoproteins (M_r 53 kDa and 21 kDa) that coprecipitated with the 65 kDa platelet type I collagen receptor. In the present investigation, we have identified one of the phosphoproteins. A soluble component the 100,000×g supernatant fraction of 53 kDa protein is recognized by polyclonal anti-PP1 antibody. The activity of the precipitated phosphatase is inhibited by okadaic acid and inhibitor 1, suggesting that it is protein phosphatase 1 (PP 1). Phosphorylation decreases PP 1 activity as was found with [³²PO4]-phosphorylase b as the substrate. The immunocoprecipitation of the type-1 collagen receptor and PP 1 inot the result of cross reactivity of the anti-type I collagen receptor antibody with the PP I protein. These results indicate that the platelet type I collagen receptor, PP 1, and unidentified 21 kDa protein are in close association with the platelet type I collagen receptor upon the binding of type I collagen by the receptor. Copyright © 1996 Elsevier Science Ltd     

Synthesis of two nitro analogs of tranylcypromine: Relations of aromatic substitution of nitro groups to MAO-Inhibitory activity

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treatingt-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate andt-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate withp-toluenesulfonic acid in CH₃CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at bothin vitro andex vivo levels. It was found fromin vitro measurements that(E)-p-NTCP at 6.0×10^?5M elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast,(E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with IC₅₀ values, 2.5×10^?7M and 1.4×10^?6M, respectively. It was also noted from(E)-m-NTCP thatm-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According toex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by(E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas,(E)-p-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between(E)-m-NTCP and(E)-p-NTCP were sought in relation to differing electron withdrawing effects ofm-andp-substituents which will influence electron density of the side chain amino functions and the partitions.     

Preventive and therapeutic effects of oral tolerance in a murine model of asthma

Allergic asthma is an inflammatory disease of the airways, and Th2 cells secreting IL-4 and IL-5 play a pivotal role in its pathogenesis. We have previously demonstrated that oral tolerance can be induced and maintained more profoundly in a Th2-related immune response, and that an ongoing immune response can be suppressed by the oral administration of antigen combined with an appropriate feeding regimen. In the present study, we examined the preventive and therapeutic effects of the oral administration of allergen on a Th2-mediated immune disorder using a murine model of asthma. Our results show that the development of asthma can be blocked completely by orally administering allergen. Airway hyperreactivity, allergen-specific IgE production, Th2-derived cytokines, allergen-induced T cell proliferation and the infiltration of inflammatory effector cells into the lung were prevented by such oral administration. To assess the therapeutic effects of oral administration on the progression of asthma, we tested the effects of oral tolerance in an established asthma model, and found that a multiple high dose-feeding regimen was effective at suppressing the progression of mild asthma. In the high dose-feeding group, the number of eosinophils in bronchoalveolar lavage fluid was reduced and airway reactivity also decreased. However, this was insufficient to reduce airway reactivity and eosinophilia in bronchoalveolar lavage fluid in cases of severe asthma. These results demonstrate that allergic asthma may be ameliorated by feeding allergen; there is hope that these results will provide a new immunotherapeutic strategy for allergic asthma.     

Cell physiology of cAMP sensor Epac

Many animal studies and human epidemiological findings have shown that impaired growth in utero is associated with physiological abnormalities in later life and have linked this to tissue programming during suboptimal intrauterine conditions at critical periods of development. However, few of these studies have considered the contribution of the placenta to the ensuing adult phenotype. In mammals, the major determinant of intrauterine growth is the placental nutrient supply, which, in turn, depends on the size, morphology, blood supply and transporter abundance of the placenta and on synthesis and metabolism of nutrients and hormones by the uteroplacental tissues. This review examines the regulation of placental nutrient transfer capacity and the potential programming effects of nutrition and glucocorticoid over-exposure on placental phenotype with particular emphasis on the role of the Igf2 gene in these processes.     

Modification of Si(100) surface by the grafting of poly(ethylene glycol) for reduction in protein adsorption and platelet adhesion

The modification of argon plasma-pretreated single-crystal Si(100) wafer surfaces via the UV-induced graft polymerization of poly(ethylene glycol) methacrylate (PEGMA) macromonomer (molecular weight approximately 340) for biomaterials applications was explored. The modified Si(100) surfaces were characterized by X-ray photoelectron spectroscopy and atomic force microscopy. Surface peroxide concentrations resulting from the argon plasma treatment and subsequent atmospheric exposure were determined by a coupling reaction with diphenylpicrylhydrazyl. The results suggested that a short plasma treatment time of 10 s and brief air exposure were sufficient for generating an optimum amount of peroxides and hydroperoxides for the subsequent UV-induced graft polymerization. The graft concentration of the PEGMA polymer increased with increasing PEGMA macromonomer concentration for the graft polymerization and with increasing UV graft polymerization time. The PEGMA graft-polymerized silicon surface with a high poly(ethylene glycol) graft concentration was very effective in preventing protein adsorption and platelet adhesion. The grafted PEGMA polymer layer on the Si(100) surface exhibited fairly good stability during storage in a buffer solution.     

Controlled elimination of intracellular H(2)O(2): regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification

The predominant enzymes responsible for elimination of hydrogen peroxide (H(2)O(2)) in cells are peroxiredoxins (Prxs), catalase, and glutathione peroxidases (GPxs). Evidence suggests that catalytic activities of certain isoforms of these H(2)O(2)-eliminating enzymes are extensively regulated via posttranslational modification. Prx I and Prx II become inactivated when phosphorylated on Thr(90) by cyclin B-dependent kinase Cdc2. In addition, the active-site cysteine of Prx I-IV undergoes a reversible sulfinylation (oxidation to cysteine sulfinic acid) in cells. Desulfinylation (reduction to cysteine) is achieved by a novel enzyme named sulfiredoxin. c-Abl and Arg nonreceptor protein tyrosine kinases associate with catalase in cells treated with H(2)O(2) by mechanisms involving the SH3 domains of the kinases and the Pro(293)PheAsnPro motif of catalase and activate catalase by phosphorylating it on Tyr(231) and Tyr(386). Similarily, GPx1 is activated by c-Abl- and Arg-mediated phosphorylation. The tyrosine phosphorylation is critical for ubiquitination-dependent degradation of catalase.     

Malignant granular cell tumor at the retrotracheal space

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The patient was a 21-year-old woman, who was 5 months pregnant. The tumor occurred in the retrotracheal space, extending from the level of the larynx to the thoracic inlet. In addition, there were multiple, variable-sized tumor nodules within both lung fields on chest CT scan. Histologically, tissue biopsied from the periphery of the tumor consisted of solid sheets of large ovoid cells with ample, eosinophilic cytoplasm, eccentric nuclei, and prominent nucleoli. Each cell showed slight atypism of the nuclei. There was a focal necrosis at the periphery of the lesion. These cells stained strongly for S-100 protein, neuron-specific enolase (NSE) and CD68. On electron microscopy, the tumor cells contained autophagic vacuoles. The patient refused further treatment and died 7 months later. The exact cause of death was not known. Until now, the diagnosis of MGCTs has been made only when metastasis and an aggressive clinical course are identified, although some observers advocate that some histologic features such as nuclear pleomorphism, necrosis, and the presence of any mitotic activity are indicative of malignancy. These histologic findings are not easily detectable in every case of MGCT, as in our case. So the diagnosis of a MGCT should be considered in cases with aggressive clinical findings and some histologic features, such as necrosis, nuclear atypism, and mitotic activities, which could suggest the malignant behavior of this neoplasm.     

The effect of an intercollegiate soccer game on maximal power performance.

The effect of a competitive soccer match on maximal power performance was assessed on 19 members of an NCAA Division III female soccer team. Performance testing occurred within 24 hours prior to the game (Pre), immediately postgame (IP), and 24 hours postgame (24P). Each subject performed a squat jump (SJ) and countermovement jump (CMJ). Comparisons between starters (n = 10) and nonstarters (n = 9) revealed no between-group differences in power performance at IP, but starters were found to have significantly lower power and force measures at 24P than nonstarters. There were significant correlations between playing time and peak force during the SJ at 24P (r = -0.47), and between playing time and peak power during the SJ at IP (r = -0.57) and 24P (r = -0.51), and during the CMJ at IP (r = -0.49). Comparisons between different positions revealed no differential fatigue patterns. Results of this study show that power performance appears to be maintained for the duration of a soccer match but declines significantly within 24 hours after the match. Position played does not appear to affect performance decrements seen at 24 hours postmatch.