肝纤维化大鼠肝窦内皮细胞整合素α6β1及粘着斑激酶表达的变化

目的研究正常及肝纤维化时大鼠肝窦内皮细胞(SEC)表面层粘连蛋白(LN)的整合素受体α 6 β 1及粘着斑激酶(FAK)的变化.方法用胶原酶原位灌注、Percoll不连续密度梯度离心法分离正常及四氯化碳(CCl4)实验性大鼠肝纤维化模型中的SEC,并进行体外培养.采用细胞-ELISA和免疫沉淀-蛋白质酪氨酸激酶活性测定的方法,分别观察SEC细胞表面整合素α 6 β 1表达及FAK活性的变化.结果正常大鼠SEC细胞表面几乎不表达整合素α6 β 1;在肝纤维化时SEC细胞表面α 6 β 1蛋白表达却明显增加(P＜0.05),且细胞中FAK活性明显增高(P＜0 05).结论在肝纤维化时SEC细胞表面整合素α 6 β 1的表达及FAK活性明显增高,可能在SEC的形态及功能改变中起重要作用.     

Investigation of relaxant effects of propofol on sheep sphincter of Oddi.

BACKGROUND/AIMS: Intravenous anesthetics are often used for conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi (SO) manometry. This study was designed to investigate the effects of propofol on sheep SO. METHODS: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to propofol (10(-8)-10(-4)M) in the presence or absence of L-NAME (3 x 10(-5)M), a non-specific inhibitor of nitric oxide (NO) synthase; indomethacin (10(-5)M), an inhibitor of cyclooxygenase; glibenclamide (10(-5)M), an inhibitor of ATP-sensitive potassium channels; tetraethylammonium (3 x 10(-4)M), inhibitors of calcium-activated potassium channels; 4-aminopyridine (10(-3)M), a voltage-dependent potassium channel blocker. Furthermore, we investigated the Ca(2+) antagonist feature of propofol in precontracted SO rings by CaCl(2). RESULTS: Carbachol (10(-9)-10(-5)M) induced concentration-dependent contraction responses in the SO rings. Propofol (10(-8)-10(-4)M) produced concentration-dependent relaxation on isolated SO rings precontracted by carbachol (10(-6)M). Preincubation of SO rings by L-NAME (3 x 10(-5)M), indomethacin (10(-5)M), glibenclamide (10(-5)M), and 4-aminopyridine (10(-3)M) did not produce a significant alteration on propofol-induced relaxation responses (p > 0.05), while preincubation by tetraethylammonium (3 x 10(-4)M) significantly decreased the propofol-induced relaxation responses (p < 0.05). Propofol (10(-8)-10(-4)M) induced concentration-dependently relaxations in precontracted isolated SO rings by CaCl(2). CONCLUSION: The results suggest that propofol induced concentration-dependent relaxations in precontracted isolated SO rings. These relaxations are independent from NO, cyclooxygenase metabolites, and opened ATP-sensitive and voltage-dependent potassium channels. Opened Ca(2+)-sensitive K(+) channels and inhibited L-type Ca(2+) channels existing in smooth muscle by propofol can contribute to these relaxations. Propofol can be beneficial as alternative drugs for obtaining selective relaxation during SO manometry after controlled clinical studies.     

Analysis of the three dimensional structure of the CXGXC motif in the CMGCC and CAGYC regions of alpha-and beta-subunits of human chorionic gonadotropin: importance of glycine residue (G) in the motif

The three dimensional structures of the C(1)X(2)G (3)(X(3))X(4)C(5) motif of hCG, which is considered to be important for noncovalent assembly of the alpha- and beta-subunits of glycoprotein hormones were analyzed to assess the importance of glycine (Gly) (G) at site X(3) in the motif by the conformational energy calculation using computational procedures. In the C(1)M(2)G (3)(X(3))C(4)C(5) motif of the alpha-subunit, Ramachandran plot analysis showing the allowed area of the dihedral angles demonstrated that only a Gly residue was allowed at site X(3). In calculating collision with surrounding atoms as a monomer the possible main chain models of the C(1)A(2)G(3)(X(3))Y(4)C(5) motif in the beta-subunit showed that only alanine (Ala) (A) or Gly at site X(3) is allowed to alleviate the collision with the cysteine (Cys) (C) residues which form a disulfide bridge. A mutant of the beta-subunit with the C(1)A(2)A(3)(X(3))Y(4)C(5) motif (Ala at site X(3)) may not compose a heterodimer with the alpha-subunit because of interference of intermolecular hydrogen bond formation. These findings indicate that the Gly residue at site X(3) (G(3)) in the motif is essential for heterodimer formation of glycoprotein hormones. The significance of similar motifs found in various human proteins other than glycoprotein hormones was suggested.     

Modulation of energy-dependent quenching of excitons in antennae of higher plants

Energy-dependent exciton quenching, or q(E), protects the higher plant photosynthetic apparatus from photodamage. Initiation of q(E) involves protonation of violaxanthin deepoxidase and PsbS, a component of the photosystem II antenna complex, as a result of lumen acidification driven by photosynthetic electron transfer. It has become clear that the response of q(E) to linear electron flow, termed "q(E) sensitivity," must be modulated in response to fluctuating environmental conditions. Previously, three mechanisms have been proposed to account for q(E) modulation: (i) the sensitivity of q(E) to the lumen pH is altered; (ii) elevated cyclic electron flow around photosystem I increases proton translocation into the lumen; and (iii) lowering the conductivity of the thylakoid ATP synthase to protons (g(H+)) allows formation of a larger steady-state proton motive force (pmf). Kinetic analysis of the electrochromic shift of intrinsic thylakoid pigments, a linear indicator of transthylakoid electric field component, suggests that, when CO(2) alone was lowered from 350 ppm to 50 ppm CO(2), modulation of q(E) sensitivity could be explained solely by changes in conductivity. Lowering both CO(2) (to 50 ppm) and O(2) (to 1%) resulted in an additional increase in q(E) sensitivity that could not be explained by changes in conductivity or cyclic electron flow associated with photosystem I. Evidence is presented for a fourth mechanism, in which changes in q(E) sensitivity result from variable partitioning of proton motive force into the electric field and pH gradient components. The implications of this mechanism for the storage of proton motive force and the regulation of the light reactions are discussed.     

Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) comprises molecularly distinct subgroups such as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCLs. We previously reported that CD5(+) and CD5(-)CD10(+) DLBCL constitute clinically relevant subgroups. To determine whether these 2 subgroups are related to ABC and GCB DLBCLs, we analyzed the genomic imbalance of 99 cases (36 CD5(+), 19 CD5(-)CD10(+), and 44 CD5(-)CD10(-)) using array-based comparative genomic hybridization (CGH). Forty-six of these cases (22 CD5(+), 7 CD5(-)CD10(+), and 17 CD5(-)CD10(-)) were subsequently subjected to gene-expression profiling, resulting in their division into 28 ABC (19 CD5(+) and 9 CD5(-)CD10(-)) and 18 GCB (3 CD5(+), 7 CD5(-)CD10(+), and 8 CD5(-)CD10(-)) types. A comparison of genome profiles of distinct subgroups of DLBCL demonstrated that (1) ABC DLBCL is characterized by gain of 3q, 18q, and 19q and loss of 6q and 9p21, and GCB DLBCL is characterized by gain of 1q, 2p, 7q, and 12q; (2) the genomic imbalances characteristic of the CD5(+) and CD5(-)CD10(+) groups were similar to those of the ABC and GCB types, respectively. These findings suggest that CD5(+) and CD5(-)CD10(+) subgroups are included, respectively, in the ABC and GCB types. Finally, when searching for genomic imbalances that affect patients' prognosis, we found that 9p21 loss (p16(INK4a) locus) marks the most aggressive type of DLBCL.     

Investigation of the relaxant effects of pinacidil and cromakalim on the sheep sphincter of Oddi.

BACKGROUND/AIMS: ATP-sensitive K+ (KATP) channels play an important role in the regulation of smooth muscle membrane potential. This study was designed to investigate the effects of pinacidil and cromakalim, KATP-sensitive channel activators, on sheep sphincters of Oddi (SO). METHODS: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to pinacidil (10(-9)-10(-4)M) and cromakalim (10(-9)-10(-4)M) in the presence or absence of glibenclamide (10(-6)M), a blocker of KATP channels. Furthermore, concentration-dependent contraction responses of carbachol were obtained. RESULTS: Carbachol (10(-9)-10(-5)M) induced concentration-dependent contraction responses in the SO rings. Pinacidil (10(-9)-10(-4)M) and cromakalim (10(-9)-10(-4)M) induced concentration-dependent relaxation in isolated SO rings precontracted with carbachol (10(-6)M). At their maximum effects, both pinacidil and cromakalim produced nearly full relaxation. In the presence of glibenclamide, concentration-relaxation curves for pinacidil and cromakalim underwent rightward parallel shifts. There were no significant differences between pEC50 and E(max) values of pinacidil and cromakalim in the absence of glibenclamide (10(-6)M) (p > 0.05), but pEC(50) values of pinacidil and cromakalim in the presence of glibenclamide (10(-6)M) were significantly reduced (p < 0.05). CONCLUSION: These results suggest that the relaxation caused in sheep SO by pinacidil and cromakalim is mediated through the same glibenclamide-sensitive KATP channel. Pinacidil and cromakalim have an equipotent relaxing effect in isolated sheep SO and they can be beneficial as alternative drugs for obtaining selective relaxation during SO manometry after controlled clinical studies.     

Law of conservation of the capital-output ratio

Just as simple harmonic motion, definable by a variational condition, delta [unk] ((1/2) x(2) - (1/2) x(2)) dt = 0, has motions which must conserve the sum of kinetic and potential energies, (1/2) x(2) + (1/2)x(2) congruent with constant, so in a neoclassical von Neumann economy, where all output is saved to provide capital formation for the system's growth, it will be true that there exists a conservation law-namely the constancy along any intertemporally-efficient motion of the capital-output ratio SigmaP(t) (j)K(t) (j)/SigmaP(t) (j)K(t) (j). This is derived as an "energy" integral of a time-free integrand(1) in an optimal-control problem of variational type.     

抑制5-脂氧合酶表达对胰腺癌细胞增殖和凋亡的影响

目的 应用RNA干扰(RNAi)技术阻断5-脂氧合酶(5-LOX)的表达,观察其对人胰腺癌细胞SW1990增殖及凋亡的作用.方法 构建4个靶向5-LOX的小干扰RNA(small interference,siRNA)和1个阴性对照siRNA质粒表达载体,采用Lipofectamine TM2000法转染SWl990细胞,RT-PCR和Western blot检测RNAi后SWl990细胞的5-LOX mRNA和蛋白表达,MTT法检测细胞的增殖抑制率,流式细胞仪检测细胞凋亡率.结果 阴性对照和4个序列特异性的siRNA对SWl990细胞5-LOXmRNA表达的抑制率分别为(3.0±1.4)%、(18.8±1.5)%、(53.5±2.3)%、(56.1±2.0)%、(52.4±2.5)%;5-LOX蛋白表达抑制率分别为(4.5±2.0)%、(18.1±2.5)%、(50.4±4.3)%、(48.9±4.4)%、(45.9±4.0)%.转染24 h后癌细胞增殖抑制率分别为(2.1±1.0)%、(5.5±1.3)%、(11.9±1.2)%、(13.4±1.1)%、(13.8±1.3)%.;48 h的增殖抑制率分别为(3.0±1.3)%、(16.0±2.2)%、(25.7±2.5)%、(25.3±3.1)%、(27.2±3.2)%.转染24 h细胞凋亡率分别为(2.0±0.8)%、(5.3±1.0)%、(10.6±1.2)%、(12.4±1.0)%、(10.6±0.9)%;转染48 h的凋亡率分别为(3.0±1.0)%、(7.1±1.1)%、(17.5±0.9)%、(21.5±1.1)%、(15.7±1.0)%.结论 通过RNAi可以有效、特异地阻断SWl990细胞5-LOX的表达,并可以有效抑制肿瘤细胞的增殖,促进肿瘤细胞凋亡.     

Effects of vasoconstrictor agents on flow rate of isolated epicardial coronary artery of humans with various degrees of atherosclerosis and of young pigs

Constriction of epicardial coronary arteries induces severe flow reduction causing myocardial ischaemia in patients with vasospastic angina. Whether such constriction is inherent in coronary arteries in general was determined by perfusing isolated epicardial coronary segments of humans and pigs at a constant perfusion pressure. Mean flow reduction after perfusion with potassium chloride (60 mmol.litre-1), acetylcholine (10(-9)-10(-5) mol.litre-1), and histamine (10(-8)-10(-4) mol.litre-1) was not different between humans and pigs. Prostaglandin F2 alpha (PGF2 alpha; 3 X 10(-6) mol.litre-1) decreased the flow more substantially in humans (by 74(9)%) than in pigs (by 6(1)%) (p less than 0.01). A pronounced flow reduction to 0 ml.min-1 was observed in eight of 17 human coronary arteries after potassium chloride, histamine, or PGF2 alpha perfusion but in none of the pigs. Histological examination of the coronary arteries showed no atherosclerotic lesions in the pigs but various lesions in humans, ranging from intimal thickening to 96% luminal stenosis in cross sectional area. Flow reduction after PGF2 alpha was significantly greater in human coronary arteries with stenoses greater than 50% (94(4)%) than in those with stenoses less than 25% (55(14)%) (p less than 0.05). Complete cessation of flow was observed more often in the stenotic arteries (greater than 50% stenosis) than in others (p less than 0.05). A substantial reduction in flow, which may cause myocardial ischaemia in vivo, was not seen in normal pig coronary arteries even after strong vasoconstrictor stimuli but was present in human coronary arteries with atherosclerosis.     

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

AIM To reveal the correlation between thefunctional differentiation phenotypes of gastriccarcinoma cells and the invasion and metastasisby a new way of cell-function classification.METHODS Surgically resected specimens of361 gastric carcinomas (GC) were investigatedwith enzyme-, mucin-, and tumor-related markerimmunohistochemistry. According to thedirection of cell-function differentiation,stomach carcinomas were divided into fivefunctionally differentiated types.RESULTS ① Absorptive function different-iation type (AFDT): there were 82 (22.7%)patients including 76 (92.7%) aged 45 years.Sixty-nine (84.1%) cases belonged to theintestinal type. Thirty-eight (46.3%) expressedCD44v6 and 9 (13.6%) of 66 male patientsdeveloped liver metastasis. The 5-year survivalrate of patients in this group (58.5%) was higherthan those with the other types (P<0.01). ②Mucin secreting function differentiation type(MSFDT): 54 (15%) cases. Fifty-three (98.1%)tumors had penetrated the serosa, 12 (22.2%)expressed ER and 22 (40.7%) expressedCD44v6. The postoperative 5-year survival ratewas 28.6%. ③ Absorptive and mucin-producingfunction differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%)aged yanger than 45 years. The tumor was morecommon in women (62, 34.4%,) and expressedmore frequently estrogen receptors (ER) (129,81.7%) than other types (P<0.01). Ovarymetastasis was found in 12 (19.4%) out of 62female subjects. The patients with this type GChad the lowest 5-year survival rate (24.7%)among all types. ① Specific functiondifferentiation type (SFDT) : 13 (3.6%) cases.Nine (69.2%) tumors of this type derived fromAPUD system, the other 4 (30.7%) were ofdifferent histological differentiation. Sixty percent of the patients survived at least five years.⑤ Non-function differentiation type (NFDT): 32(8.9%) cases. Nineteen (59.4%) cases hadlymph node metastases but no one with liver orovary metastasis. The 5-year survival rate was28.1%.CONCLUSION This new cell-functionclassification of GC is helpful in indicating thecharacteristics of invasion and metastasis of GCwith different cell-function differentiationphenotypes, Further study is needed to disclosethe correlation between the cell-functionaldifferentiation phenotypes and the relevantgenotypes and the biological behavior of gastriccarcinoma.     

Controlled study of the effect of nicardipine and ceruletide on the sphincter of Oddi.

Although sphincter of Oddi dysfunction is a recognised cause of post cholecystectomy pain, the control mechanisms involved in sphincter of Oddi function are poorly understood. Pharmacological relaxation of the sphincter of Oddi may have a beneficial effect particularly in sphincter of Oddi dysfunction where basal sphincter pressure is high. The aim of this study was to investigate the effects of calcium channel blockade (nicardipine) and synthetic cholecystokinin (ceruletide) on sphincter of Oddi pressures. Nineteen patients (median age 49 years; range 21-75) attending for routine endoscopic retrograde cholangiopancreatographic (ERCP) examination were studied. No patients with evidence of sphincter of Oddi dysfunction were included in the study. Each patient was randomly allocated to receive a three minute intravenous infusion of nicardipine 3 mg (six) ceruletide 5 ng/kg (seven) or placebo (six). Endoscopic biliary manometry was done with recording of basal sphincter of Oddi pressures, sphincter of Oddi phasic wave amplitude and frequency before and after intravenous infusions. In the nicardipine group patients showed a decrease in both basal and phasic amplitude sphincter of Oddi pressure (mm Hg) from the preinfusion values (mean (SEM)) of 24.7 (3.6) and 112.3 (13.4) to 12.9 (2.9) (p less than 0.01) and 89.9 (12.4) (p less than 0.03) after infusion respectively. Ceruletide produced a decrease in sphincter of Oddi phasic wave frequency (c/min) from 3.4 (0.3) before infusion to 2.6 (0.5) after infusion (p less than 0.05). We conclude that nicardipine effectively decreases sphincter of Oddi pressure. This drug may therefore be of value in the treatment of sphincter of Oddi dysfunction where raised sphincter pressures are thought to be the primary pathogenic feature.     

Biregular classification of Fano 3-folds and Fano manifolds of coindex 3

The Fano 3-folds and their higher dimensional analogues are classified over an arbitrary field k [unk] C by applying the theory of vector bundles (in the case B(2) = 1) and the theory of extremal rays (in the case B(2) >/= 2). An n-dimensional smooth projective variety X over k is a Fano manifold if its first Chern class c(1)(X) epsilon H(2)(X, Z) is positive in the sense of Kodaira [Kodaira, K. (1954) Ann. Math. 60, 28-48] (or ample). If n = 3 and c(1)(X) generates H(2)(X, Z), then either (i) X is a complete intersection in a Grassmann variety G with respect to a homogeneous vector bundle E on G: the rank of E is equal to codim(G)X and X is isomorphic to the zero locus of a global section of E, (ii) X is a linear section of a 10-dimensional spinor variety X(12) (10) [unk] P(k) (15), or (iii) X is isomorphic to a double cover of P(k) (3), a 3-dimensional quadric Q(k) (3), or a quintic del Pezzo 3-fold V(5) [unk] P(k) (6). If n = 4 and c(1)(X) is divisible by 2, then X [unk] C is isomorphic to (a) a complete intersection in a homogeneous space or its double cover, (b) a product of P(1) and a Fano 3-fold, (c) the blow-up of Q(4) [unk] P(5) along a line or along a conic, or (d) a P(1)-bundle compactifying a line bundle on P(3) or on Q(3) [unk] P(4).     

Role of thyrotropin in metabolism of thyroid hormones in nonthyroidal tissues

T(4) conversion into T(3) in peripheral tissues is the major source of circulating T(3). However, the exact mechanism of this process is ill defined. Several in vitro studies have demonstrated that thyrotropin facilitates deiodination of T(4) into T(3) in liver and kidneys. However, there is a paucity of in vitro studies confirming this activity of thyrotropin. Therefore, this study was conducted to examine the influence of thyrotropin on thyroid hormone metabolism in nonthyroidal tissues. We assessed T(4), T(3), reverse T(3) (rT(3)), and T(3) resin uptake (T(3)RU) responses up to 12 hours at intervals of 4 hours in 6 thyroidectomized female mongrel dogs rendered euthyroid with LT(4) replacement therapy before and after subcutaneous (SC) administration of bovine thyrotropin (5 U) on one day and normal saline (0.5 mL) on another in a randomized sequence between 08:00 and 09:00 am. Euthyroid state after LT(4) replacement was confirmed before thyrotropin administration. Serum T(4), T(3), rT(3), and T(3)RU all remained unaltered after SC administration of normal saline. No significant alteration was noted in serum T(3)RU values on SC administration of thyrotropin. However, serum T(3) rose progressively reaching a peak at 12 hours with simultaneous declines being noted in both serum T(4) and rT(3) concentrations (P < .05 vs prethyrotropin values for all determinations). The changes after SC administration were significantly different (P < .001) in comparison to those noted on SC administration of normal saline. Thyrotropin may promote both the conversion of T(4) to T(3) and metabolism of rT(3) into T(2) in nonthyroidal tissues via enhancement of the same monodeionase.     

犬Marshall韧带心肌细胞电生理特性的研究

目的　研究Marshall韧带(ligamentofMarshall, LOM)内心肌细胞的电生理特性。方法　组织块酶解法分离犬LOM内单个心肌细胞,在倒置显微镜下直接比较细胞形态;采用全细胞膜片钳技术记录心肌细胞动作电位的时程 (APD90,APD50 )和振幅 (APA),测量ICa,L、Ito、IK1、IK、INa等离子电流密度。结果　LOM内有两种不同形态的心肌细胞:一种为短矩形,另一种为长杆形,两者的长宽比分别为 2 .99±0. 95和 12. 05±2 .41,P<0. 01。两种形态细胞均表现为快反应动作电位,短矩形细胞的APA(mV)、APD50 (ms)和APD90 (ms)均小于长杆形细胞,分别为 80. 02±3 .68比 91 .72±7. 56、69 .62±6 .33比 83. 14±3 .66和 107. 55±4 .25比 144. 00±5 .15,P<0 .05。两种细胞的INa、ICa,L、Ito、IK1等离子的电流密度差异有统计学意义。结论　Marshall韧带中肌细胞呈现两种形态,并且在动作电位及许多离子电流密度上存在差异,两者的细胞电生理呈不均一性。     

氟对大鼠腰椎骨组织形态计量学的影响

目的 观察氟对大鼠腰椎的骨组织形态计量学影响.方法 90只2月龄SPF级SD大鼠,雌雄各半,按体质量随机分成9组,其中对照组分为幼年(CS)、成年(AS)、长期(NS)组,用药组分为幼年高氟(CHS)、幼年低氟(CIS)、成年高氟(AHS)、成年低氟(ALS)、幼年长期高氟(CLHS)、幼年长期低氟(CLLS)组.对照组生理盐水灌胃,用药组分别按相应时间给予不同剂量的氟化钠灌胃.实验验结束后,取腰椎制成不脱钙骨切片,行骨组织形态计量学测量.包括骨小粱面积百分数(Tb.Ar)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、单位骨小梁面积破骨细胞数(Oc.N)、破骨细胞周长百分数(%Oc.Pm)、荧光周长百分率(%L.Pm)、骨矿化沉积率(MAR)、骨小梁周长形成率(BFR/BS)、骨小梁面积形成率(BFR/BV)、骨组织总面积形成率(BFR/TV)、成骨细胞周长(Ob.PM).结果 [1]CHS组的%Tb.Ar、Tb.Th、Tb.N、%L.Pm、MAR、BFR/BS、BFR/BV、和BFR/TV[(50.63±7.44)%,(150.26±27.51)μm,(3.44±0.47)N/mm,(50.63±7.44)%,(0.85±0.03)μm/d、(8.45±2.36)μm/d×100、(381.16±41.62)%/year、(75.07±4.81)%/year]均高于CS组[(29.71±9.32%)、(1 10.93±28.19)μm、(2.68±0.34)N/mm、(24.00±1.22)%、(0.65±0.03)μm/d、(5.43±0.18)μm/d×100、(141.32±9.29)%/year、(58.14±2.3)%/year,P<0.05].CLS组的%Tb.A、Tb.Th、%L.Pm、MAR、BFR/BS、BFR/BV、BFR/TV和Ob.PM[(40.76±6.43)%、(164.25±45.65)μm、(42.02±6.12)%、(0.85±0.04)μm/d、(8.95±3.73)μm/d×100、(378.73±35.39)%/year、(73.52±8.71)%/year、(1.41±0.05)μm]均高于CS组(P均<0.05).[2]AHS组的%Tb.Ar、Oc.N、%Oc.Pm、%L.Pm、MAR、BFR/BS、BFR/BV和BFR/TV[(50.62±5.76)%、(0.51±0.05)N/mm、(1.13±0.05)%、(42.3±7.02)%、(1.28±0.09)μm/d、(12.91±1.52)μm/d×100、(390.12±43.56)%/year、(65.21±22.13)%/year]均高于AS组[(42.73±5.22)%、(0.41±0.17)N/mm、(0.77±0.52)%、(28.43±6.93)%、(0.80±0.03)μm/d、(9.83±1.44)μm/d ×100、(324.43±53.44)%/year和(48.35±9.36)%/year,P均<0.05].A15组的%Tb.Ar、Oc.N、%Oc.Pm、%L.Pm、MAR、BFR/BS、BFR/BV和BFR/TV[(51.14±6.22)%、(O.49±0.61)N/mm、(1.17±0.11)%、(45.06±6.92)%、(1.39 ±0.08)μm/d、(12.87±1.35)μm/d × 100、(394.6±50.23)%/year和(66.31±18.93)%/year]均高于AS组(P均<0.05).[3]CLHS组的Ob.PM、Oc.N和%Oc.Pm[(1.47±0.27)μm、(0.58±0.13)N/mm、(1.14±0.07)%]均高于NS组[(0.82±1.2)μm、(0.42±0.25)N/mm和(0.75±0.64)%,P均<0.05)].结论 短期染氟导致幼年、成年大鼠的腰椎成骨活动增强;长期染氟虽然增加成骨细胞数目,但是腰椎骨量增加不明显,有促进骨吸收,降低骨质量的可能,随着氟化钠使用时间的延长,逐渐表现出对生长期大鼠骨代谢和骨质量的负作用.     

The features of cases of intrathoracic lymphomas

In this study, 18 patients who had been diagnosed as intrathoracic lymphoma between January 1999 and August 2001 had been evaluated retrospectively to guide the diagnostic approaches. 12 (66.6%) of the patients were male and 6 (33.4%) were female. The mean age was 46.47 +/- 17.31. The leading symptoms were disapnea, cough, weight loss and fever. The most frequently seen laboratory findings were decreased hemoglobin and hematocrit rates (72.2%) and increased Lactate Dehydrogenase levels (44.4%). Radiologically, 18 (100%) patients had mediastinal lymph node enlargement, 8 (44.4%) patients had bilateral and 6 (33.3%) had unilateral hilar enlargement, 3 (16.6%) patients had appearance of mass lesion, 1 (5.5%) had appearance of consolidation, 2 (11.1%) patients had atelectasis, 3 (16.6%) patients had appearance of pleural effusion. Histopathological diagnosis were undertaken with lymph node biopsies in 11(61.1%) patients, with bronchial biopsies in 2 (11.1%) patients, with pleural biopsy in 1 (5.5%) patient, with lymph node and bronchial biopsies in 3 (16.6%) patients, with lymph node and pleural biopsies in 1 (5.5%) patient. 11 (61.1%) patients were diagnosed as Hodgkin Disease (nine as nodular type, two as mixed cellular type). 7 (38.9%) patients were diagnosed as non Hodgkin Lymphoma. After taking diagnosis the patients were sent to medical oncology clinics for follow up and therapy. These findings showed that different locations of intrathoracic lymphomas could be seen with nodal or extranodal presentations so it must be taken into account in differential diagnosis of other pathological conditions.     

阿尔茨海默病的~(18)F-FDDNP脑断层扫描显像

目的探讨标记物18F-FDDNP在脑断层扫描(PET)显像中诊断阿尔茨海默病(AD)的价值。方法分别对7例AD患者(AD组)、6例血管性痴呆(VaD)患者(VaD组)及6例智能正常老年对照者(NC,NC组)进行18F-FDDNP脑PET显像,受试者分别在药物注射后5 min2、5 min和45 min采集图像。结果AD患者3个时段放射性清除情况与其他2组图像有明显的不同。药物注射45 min后脑内放射性清除率较VaD组、NC组明显减低。结论18F-FDDNP脑PET显像是诊断AD的一个有效的影像学指标。     

热量限制对人二倍体成纤维细胞衰老相关基因表达的影响

目的观察热量限制对人二倍体成纤维细胞IMR-90衰老相关基因表达的影响。方法应用RT-PCR和Western blot的方法，对含低浓度（3．0mmol／L）、高浓度（22．5mmol／L）葡萄糖和正常对照组（含5．0mmol／L葡萄糖）培养条件下的IMR-90细胞衰老相关基因p16、p21和p53的mRNA和蛋白表达水平进行分析。结果与对照组和高糖培养条件下的早期和晚期细胞相比较，低浓度葡萄糖培养条件下的早期和晚期细胞p16和p21在mRNA水平均显著下降（P〈0．05）；低浓度葡萄糖组、对照组和高浓度葡萄糖培养组晚期细胞p16蛋白水平分别为4．2、7．4、9．7，比各自早期细胞表达（0．6、1．0、1．8）增加5～7倍；低浓度葡萄糖组，对照组和高浓度葡萄糖培养早期细胞和低糖培养晚期细胞p21蛋白水平差异无统计学意义，分别为1．1、1．0、1．3、0．9，但与对照组和高糖培养晚期细胞p21蛋白水平（3．1、4．2）相比较则降低3～4倍；各组培养条件下的早期和晚期细胞中p53表达差异均无统计学意义（P〉0．05）。结论各组晚期细胞比各自早期细胞p16基因表达增高；对照组和高糖培养条件下的晚期细胞比各自早期细胞p21基因表达增高；低浓度葡萄糖培养延缓IMR-90细胞衰老并伴有p16和p21基因表达下调；p53基因可能不是IMR-90细胞复制衰老主要调节因子。     

Role of C-terminal domains of the G protein beta subunit in the activation of effectors

The prenyl group on the G protein gamma subunit is an important determinant of protein-protein interactions between the betagamma dimer and its targets, such as alpha subunits, receptors, and effectors. In an effort to identify domains of the beta subunit important for the activation of effectors, we have prepared two types of mutants, one set in the domain suggested to form a hydrophobic prenyl-binding pocket for the gamma subunit's prenyl group (prenyl pocket mutants) and the other set in a domain between Gly(306) and Gly(319) in the beta propeller, which undergoes a conformational change when the dimer binds to phosducin (conformational change mutants). Recombinant baculoviruses for each set of mutants were prepared, and the nine mutant beta subunits were overexpressed with either the gamma(2) subunit (modified with geranylgeranyl) or the gamma(2-L71S) subunit (gamma(2) with altered CAAX sequence and modified with farnesyl). The purified dimers were tested for their ability to couple Galpha(i1) to the A1 adenosine receptor and to activate phospholipase C-beta or type II adenylyl cyclase. All dimers containing mutant beta subunits were indistinguishable from wild-type beta(1)gamma(2) or beta(1)gamma(2-L71S) in coupling the receptor to Galpha(i1). The prenyl pocket mutants expressed with gamma(2) were 10-fold less potent in activating phospholipase C-beta and adenylyl cyclase than beta(1)gamma(2) and had similar activities to beta(1)gamma(2-L71S). The conformational change mutants caused a 15- to 23-fold decrease in EC(50) values for activation of these two effectors. Overall, the results suggest that the sites in Gbeta identified by these mutants are very important in the activation of effectors. Furthermore, the nature of the prenyl group on Ggamma may play an important role in the conformational change leading to the activity of Gbetagamma on effectors.     

Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity

Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro(39)Pro and Ile(178)Ile) and three nonsynonymous variants (Ala(242)Ser, Arg(517)Cys, and Gly(532)Val). Furthermore, the rare Ala(242)Ser was identified in two families and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and Arg(517)Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.