Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis

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多种金属离子与单宁酸反应媒染微血管的对比研究

目的　镜下观察单宁酸与金属盐溶液中Ca2 + 、Au+ 、Ag+ 、Pb2 + 、Cu2 + 、Al3 + 、U6+ 、K+ 联用显示大脑微血管的效果。方法　用单宁酸媒染固定液灌流大鼠 ,取脑切片 ,入氯化钙、氯化金、硝酸银、硝酸铅、硫酸铜、硫酸铝钾、醋酸双氧铀、高锰酸钾和重铬酸钾等溶液中呈色。结果　单宁酸与Ca2 + 、Cu2 + 、Ag+ 、Al3 + 结合显示血管清晰 ,与Au+ 、U6+ 、Pb2 + 、K+ 联用媒染血管效果欠佳。结论　含Ca2 + 、Cu2 + 、Ag+ 、Al3 + 的金属盐类可替代氯化铁媒染微血管 ,氯化金、醋酸双氧铀、硝酸铅、重铬酸钾和高锰酸钾不宜与单宁酸联用来显示血管     

Heavy-ion-induced mutations in the gpt delta transgenic mouse: comparison of mutation spectra induced by heavy-ion,X-ray,and gamma-ray radiation

Heavy-ion radiation accounts for the major component of absorbed cosmic radiation and is thus regarded as a significant risk during long-term manned space missions. To evaluate the genetic damage induced by heavy particle radiation, gpt delta transgenic mice were exposed to carbon particle irradiation and the induced mutations were compared with those induced by reference radiations, i.e., X-rays and gamma-rays. In the transgenic mouse model, deletions and point mutations were individually identified as Spi(-) and gpt mutations, respectively. Two days after 10 Gy of whole-body irradiation, the mutant frequencies (MFs) of Spi(-) and gpt were determined. Carbon particle irradiation significantly increased Spi(-) MF in the liver, spleen, and kidney but not in the testis, suggesting an organ-specific induction of mutations by heavy-ion irradiation. In the liver, the potency of inducing Spi(-) mutation was highest for carbon particles (3.3-fold increase) followed by X-rays (2.1-fold increase) and gamma-rays (1.3-fold increase), while the potency of inducing gpt mutations was highest for gamma-rays (3.3-fold increase) followed by X-rays (2.1-fold increase) and carbon particles (1.6-fold increase). DNA sequence analysis revealed that carbon particles induced deletions that were mainly more than 1,000 base pairs in size, whereas gamma-rays induced deletions of less than 100 base pairs and base substitutions. X-rays induced various-sized deletions and base substitutions. These results suggest that heavy-ion beam irradiation is effective at inducing deletions via DNA double-strand breaks but less effective than X-ray and gamma-ray irradiation at producing oxidative DNA damage by free radicals.     

Ca2+ and Sr2+ activation: Comparison of cardiac and skeletal muscle contraction models

The mechanism of contraction in rabbit fast-twitch, and bovine and rabbit cardiac muscle was examined using functionally skinned fibers, ATPase activity of myofibrils, and cardiac or skeletal troponintropomyosin regulated actin heavy meromyosin. The Ca²⁺ and Sr²⁺ activation properties for the different measures of contraction were evaluated. (1) Tension in rabbit and bovine cardiac skinned fibers and rabbit cardiac myofibrillar ATPase were activated equally well by either Ca²⁺ or Sr²⁺. By contrast, rabbit adductor magnus (fast-twitch) skinned fibers required substantially higher [Sr²⁺] than [Ca²⁺] for activation, as did rabbit myofibrils from back muscle (fast-twitch). (2) Substantially more Sr²⁺ than Ca²⁺ was also required for activation of skeletal muscle actin heavy meromyosin ATPase, controlled by either the skeletal or cardiac troponin-tropomyosin complex, similar to the activation of fast-twitch muscle. (3) The absence of correlation between the divalent cation selectivity properties of actin heavy meromyosin ATPase controlled by cardiac troponin-tropomyosin and cardiac muscle tension or myofibrillar ATPase activation by Ca²⁺ and Sr²⁺ suggests that troponin, if primarily responsible for the activation of cardiac muscle, has very different in vivo and in vitro binding properties. (4) The close correlation between percentage of maximal Ca²⁺- and Sr²⁺-activated myofibrillar ATPase and tension in skinned fibers strongly justifies the use of myofibrillar ATPase, in contrast to a reconstituted troponin-tropomyosin actin heavy meromyosin ATPase system, as a biochemical measure of contraction.     

Correlation between percentage fiber type area and myosin heavy chain content in human skeletal muscle

Histochemical methods are routinely used to delineate skeletal muscle fiber types. In the present investigation, this qualitative determination of fiber type composition was compared to the electrophoretically determined myosin heavy chain (MHC) content from a large number of human muscle biopsy samples. Biopsies were taken from the vastus lateralis muscle at the beginning and every 2 weeks during 8 weeks of highi-ntensity resistance training from men (n = 13) and woman (n = 8). Muscle was also extracted from nontraining men (n = 7) and women (n = 5) at the same periods. Six muscle fiber types (I, IC, IIAC, IIA, IIAB, and IIB) were determined using basic myofibrillar adenosine triphosphatase histochemistry. Cross-sectional areas were determined for the three major fiber types (I, IIA, and IIB) and used to calculate the percentage area of these types. Electrophoretic techniques were used to separate and quantify the percentage MHC content in these same biopsy samples, and these data were then used to compare with the percentage fiber type area. Correlation analyses suggest a relationship between the histochemically assessed percentage fiber type area and the electrophoretically assessed MHC content in human limb musculature. However, because of possible histochemical misclassification of some fibers (especially in trained muscle) both techniques may be essential in yielding important information about fiber type composition and possible fiber type transformations.     

Characterization of idiotopes on MOPC 315 IgA using monoclonal antiidiotypic antibodies

The isologous antiidiotypic response in BALB/c mice to immunization with the DNP-binding IgA myeloma protein, MOPC 315, alters the expression of the anti-DNP antibody repertoire and confers immunity against MOPC 315 myeloma tumors. In order to characterize the idiotopes on MOPC 315 IgA which elicit this response we have isolated four monoclonal antiidiotypic antibodies (AIA), D10 (IgG_2a), A2(IgG₁), G3 (IgG_2b) and F1 (IgG_2a), produced by splenocytes of BALB/c mice immunized with MOPC 315 IgA in three independent fusion experiments. These AIA react with MOPC 315 IgA. reassociated H³¹⁵ L³¹⁵ and F³¹⁵_V but not with free H³¹⁵, L³¹⁵, V³¹⁵_H or V³¹⁵₂. In addition the AIA do not react with the closely related DNP-binding IgA myeloma protein, MOPC 460, suggesting that they are directed against private idiotopes on MOPC 315 IgA. These idiotopes can be divided into two groups. Group I, defined by D10, A2 and G3 consists of two overlapping idiotopes, one of which is related to the hapten-binding site. The two idiotopes are formed by an interaction of amino acids in H³¹⁵ and L³¹⁵. Group II defined by F1 consists of one idiotope which is related to the hapten-binding site. This idiotope is comprised of an aminoacid sequence on H³¹⁵ which requires an interaction with either L³¹⁵ or L⁴⁶⁰ for expression. A2 and G3 react identically with the same idiotope but were derived from two independent fusion experiments. This indicates an identity of AIA clonotypes among individual mice and suggests that the isologous AIA response to MOPC 315 IgA is restricted.     

Regulation and chance in the ontogeny of B and T cell antigen receptor repertoires

The adaptive immune system has to economically generate a large array of T and B cell antigen receptors (T cell receptors [TCRs], B cell receptors [BCRs]) that eliminate both longstanding and novel antigens from the host while preventing the production of deleterious (e.g., autoreactive) antigen receptors. Our studies focus on the mechanisms that shape the development of these antigen receptor repertoies during human ontogeny. The key to BCR and TCR diversity is the third complementarity determining region (CDR3) of the variable domain, which in the immunoglobulin heavy chain and TCR β chain, is created by the junction between the variable, diversity, and joining gene segments. The CDR3 diversity is constrained by overrepresentation of gene segments and lack of N regions during the first trimester of gestation and then increases exponentially during ontogeny until it reaches adult levels months after birth. This process parallels, and may contribute to, the stepwise acquisition of the ability to respond to specific antigens. Recent studies indicate that maturation of the CDR 3 repertoire is not accelerated by premature exposition to extrauterine antigen and thus appears to follow a strictly developmentally regulated program whose pacemaker(s) is still unknown.     

Energy state and myosin heavy chain isoforms in single fibres of normal and transforming rabbit muscles

 Energy-rich phosphates, [ATP]/[ADP_free] ratios, and the myosin heavy chain (MHC) complement were determined in single fibres from normal rabbit muscles, and in fibres isolated from tibialis anterior muscle undergoing fast-to-slow conversion by chronic low-frequency stimulation (CLFS). In normal muscles, energy-rich phosphate contents and [ATP]/[ADP_free] ratios could thus be assigned to different MHC-based fibre types. Phosphocreatine (PCr) contents and [ATP]/[ADP_free] ratios differed markedly between fast- and slow-twitch fibres, as well as within the fast fibre subtypes. Both magnitudes were approximately twofold higher in the fastest (type IIB) fibres as compared to the slowest (type I) fibres. According to PCr contents and [ATP]/[ADP_free] ratios pure and hybrid fibres were aligned in an order similar to that determined by their contractile properties and myofibrillar ATPase activities. CLFS for up to 30 days induced pronounced decreases in PCr and [ATP]/[ADP_free] which attained levels twofold lower than in normal slow-twitch fibres. In both normal and stimulated muscles, PCr and [ATP]/[ADP_free] ratios were correlated, indicating their equilibrium in the different fibre types. The relationship detected between MHC isoform expression and the [ATP]/[ADP_free] ratio suggests that the drastic and persistent depression of the cellular energy state may act as an important signal initiating fast-to-slow transformation processes in muscle fibres. Received: 26 June 1998 / Accepted: 31 July 1998     

伊贝沙坦对血管紧张素Ⅱ所致心肌细胞蛋白质合成和肌球蛋白重链表达的影响

目的 观察伊贝沙坦对血管紧张素Ⅱ（AngⅡ）所致心肌细胞中蛋白质合成速率及肌球蛋白重链（MHC）基因表达改变的影响.方法 以AngⅡ及伊贝沙坦分别或同时作用于培养的细胞.采用放射性同位素[^3H]-leu掺入法检测培养心肌细胞蛋白质合成速率.应用荧光定量PCR方法检测心肌细胞心房利钠肽因子（ANF）以及α-MHC、β-MHC的表达.结果 AngⅡ处理使心肌细胞中[^3H]-Leu掺人增加（P＜0.05）,同时ANF mRNA的表达明显高于正常（P＜0.05）;α-MHC mRNA的表达显著低于正常（P＜0.05）,而β-MHC mRNA的表达显著高于正常（P＜0.05）,α-MHC/β-MHC的比值下降（P＜0.05）.当伊贝沙坦与AngⅡ共同作用于培养的心肌细胞时,与AngⅡ组比较,[^3H]-Leu的掺入明显下降（P＜0.05）,与正常组比无统计学意义（P＞0.05）;同时ANF的表达下降,与正常组比无统计学意义（P＞0.05）;心肌细胞中α-MHC的表达明显增高（P＜0.05）,而β-MHCmRNA的表达显著降低（P＜0.05）,α-MHC/β-MHC的比值上升（P＜0.05）.结论 伊贝沙坦能抑制AngⅡ所致的心肌细胞肥大和细胞中α-MHC向β-MHC表达的转换.