Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG-CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is related to stage of infection

The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.     

丙二醛(MDA)对小鼠游泳能力的影响

MDA是脂质过氧化的重要中间产物之一,常用于表征氧化紧张.采用昆明小鼠(KMMice)研究MDA对整体动物的应激反应,考察一次性给药后小鼠的体重变化和游泳能力,结果发现:给药后10min,注射生理盐水(0.85%)能增加小鼠的体重,注射MDA(200mmol/L,0.01mL/g体重)能提高小鼠的游泳能力,二者均达到显著水平(P<0.05).这一结果对于了解氧应激疲劳和解释相关的体力恢复生化机制,具有一定的临床指导意义.     

两种人乳腺癌裸鼠移植模型的建立

目的建立简便的人乳腺癌裸鼠移植模型,并探讨其部分生物学特性。方法采用雌激素受体阴性的MDA-MB-231和SK-BR-3人乳腺癌细胞株,分别接种于10只裸鼠左侧腋窝皮下,移植细胞总数为1×107/只。观察肿块生长情况,第42天处死荷瘤鼠,切除肿块作病理切片。结果 MDA-MB-231接种后第5d在接种部位可见结节,成瘤率为90%（9/10）,接种42 d肿瘤体积426.6±333.8,瘤重0.417±0.276,病理学检查为浸润性导管癌;SK-BR-3接种后第11天在接种部位可见结节,成瘤率为80%（8/10）,接种42 d肿瘤体积357.5±246,瘤重0.325±0.167,病理学检查为浸润性导管癌。结论该方法建立的人乳腺癌裸鼠移植模型,皮下移植方法简单,易于操作,成功率较高,肿瘤可部分保持人乳腺癌生物学特性,为研究人乳腺癌提供了重要工具。     

Laboratory pesticide screening method for the aphid predatory midge Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae)

A laboratory pesticide screening method is described for the aphid predatory midge Aphidoletes aphidimyza. Four acaricides, 10 fungicides, 11 insecticides and one herbicide, all of which are in common usage, were evaluated against both the adult and larval stages of the predator. The acaricide dienochlor, the fungicides benomyl, bupirimate, chlorothalonil, iprodione and hexaconazole, the herbicide tralkoxydim and the insecticides Bacillus thuringiensis and diflubenzuron were all safe to both adult and larval A. aphidimyza. Adults were more susceptible to the pesticides than larvae. Pesticide was exposed to adults as a residue on glass plates and to larvae on a leaf section mounted on agar. The leaf material remained healthy and supported host aphids for several days without deteriorating. The method and apparatus have potential for use with many other pests and beneficial organisms required to be caged for several days on detached leaf material.     

人ApoE转基因小鼠与TGE_（7－2） TGE_（7－3）转基因鼠系的建立

用含小鼠金属硫蛋白（ＭＴ－１）基因启动子与突变的人ＡｐｏＥ７基因的６．０ＫｂＤＮＡ片段作为目的基因制备转基因小鼠,利用显微注射法将目的基因导入４４１枚受精卵,移植于２０只假孕鼠,其中１５只受孕,共产仔鼠８０只,经ａ－３２Ｐ斑点杂交与Ｓｏｕｔｈｅｒｎ杂交法鉴定出两只整合有人ＡｐｏＥ基因的转基因雌鼠,其拷贝数分别为２和５。将两只首建鼠（雌性Ｆｏ代）与正常雄鼠交配,建立Ｆ１代转基因鼠系ＴＧＥ７－２和ＴＧＥ７－３,为进一步从整体上研究ＡｐｏＥ在脂质代谢中的作用以及ＡｐｏＥ与动脉粥样硬化和Ａｌｚｈｅｉｍｅｒ’ｓ病的关系创造条件。     

The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3) in Huntington’s Disease Mice

An important epigenetic modification in Huntington’s disease (HD) research is histone acetylation, which is regulated by histone acetyltransferase and histone deacetylase (HDAC) enzymes. HDAC inhibitors have proven effective in HD model systems, and recent work is now focused on functional dissection of the individual HDAC enzymes in these effects. Histone deacetylase 3 (HDAC3), a member of the class I subfamily of HDACs, has previously been implicated in neuronal toxicity and huntingtin-induced cell death. Hence, we tested the effects of RGFP966 ((E)-N-(2-amino-4-fluorophenyl)-3-(1-cinnamyl-1H-pyrazol-4-yl)acrylamide), a benzamide-type HDAC inhibitor that selectively targets HDAC3, in the N171-82Q transgenic mouse model of HD. We found that RGFP966 at doses of 10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration, accompanied by neuroprotective effects on striatal volume. In light of previous studies implicating HDAC3 in immune function, we measured gene expression changes for 84 immune-related genes elicited by RGFP966 using quantitative PCR arrays. RGFP966 treatment did not cause widespread changes in cytokine/chemokine gene expression patterns, but did significantly alter the striatal expression of macrophage migration inhibitory factor (Mif), a hormone immune modulator associated with glial cell activation, in N171-82Q transgenic mice, but not WT mice. Accordingly, RGFP966-treated mice showed decreased glial fibrillary acidic protein (GFAP) immunoreactivity, a marker of astrocyte activation, in the striatum of N171-82Q transgenic mice compared to vehicle-treated mice. These findings suggest that the beneficial actions of HDAC3 inhibition could be related, in part, with lowered Mif levels and its associated downstream effects.     

Functional Effects of a Restrictive-Cardiomyopathy-Linked Cardiac Troponin I Mutation (R145W) in Transgenic Mice

The human cardiac troponin I (hcTnI) mutation R145W has been associated with restrictive cardiomyopathy. In this study, simultaneous measurements of ATPase activity and force in skinned papillary fibers from hcTnI R145W transgenic mice (Tg-R145W) were explored. Tg-R145W fibers showed an ∼ 13-16% increase in maximal Ca²⁺-activated force and ATPase activity compared to hcTnI wild-type transgenic mice. The force-generating cross-bridge turnover rate (g) and the energy cost (ATPase/force) were the same in all groups of fibers. Also, the Tg-R145W fibers showed a large increase in the Ca²⁺ sensitivity of both force development and ATPase. In intact fibers, the mutation caused prolonged force and intracellular [Ca²⁺] transients and increased time to peak force. Analysis of force and Ca²⁺ transients showed that there was a 40% increase in peak force in Tg-R145W muscles, which was likely due to the increased Ca²⁺ transient duration. The above cited results suggest that: (1) there would be an increase in resistance to ventricular filling during diastole resulting from the prolonged force and Ca²⁺ transients that would result in a decrease in ventricular filling (diastolic dysfunction); and (2) there would be a large (approximately 53%) increase in force during systole, which may help to partly compensate for diastolic dysfunction. These functional results help to explain the mechanisms by which these mutations give rise to a restrictive phenotype.     

Levels of Endogenous lnterleukin-1, Interleukin-6, and Tumor Necrosis Factor in Congenic Mice Infected with Borrelia garinii

This study describes the levels of interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) in the sera and parenchymal organs of various congenic mouse strains infected with Borrelia garinii. A significant elevation of inflammatory cytokine levels was found in the organs of C3H/HeN (H-2^k) and B10.BR (H-2^k) mice but not in those of BALB/c mice (H-2^d). Focally produced cytokines can contribute to antimicrobial defense against these organisms. High levels of IL-1α were observed in the sera of C3H/HeN, B10.BR and B10 (H-2^b) mice infected with B. garinii and they were associated with the presence of spirochetes in the skin. Thus, susceptible mice demonstrated a stronger cytokine response than resistant mice. This study presents in vivo evidence that B. garinii infection affects the immunopathogenesis of Lyme disease.     

Effects of Estrogen on Activity and Fear-Related Behaviors in Mice

Estrogen has been shown to affect nonreproductive behaviors in humans and rodents, including anxiety, fear, and activity levels. Rat studies have shown increases and decreases in these behaviors. Inconsistencies may be due to differences in testing conditions and the extent to which each test measures anxiety, fear, or activity. Few mouse studies have been performed. The present study was conducted to address these issues by examining the effect of estradiol benzoate (EB) in ovariectomized (OVX), C57BL/6 mice on a range of behavioral paradigms measuring anxiety [open field (OF), dark-light transition (DLT), elevated plus maze (EP)], activity [running wheel (RW)], and conditioned fear learning (FCon). In OF, vehicle (Veh) animals spent more time in the center than EB-treated animals and were more active overall. In DLT, Veh animals were more active than EB-treated animals in both the dark and light compartments and made more transitions between the two. In EP, Veh animals entered a greater number of arms. During FCon, EB animals froze more than Veh to the conditioned stimulus. In contrast, in the home cage RW, EB animals were more active than Veh. Factor analysis was used to characterize intertask correlations of females' behavior and to explore the possibility that estrogen may have an impact on a general arousal factor. In sum, estrogen treatment heightened fear responses in a range of fear and anxiety-provoking situations (OF, DLT, EP, and FCon), while increasing activity in the safer RW. We suggest that EB treatment may result in a generally more aroused animal.     

紫杉醇联合卡铂治疗局部晚期乳腺癌的临床研究

目的:探讨紫杉醇联合卡铂治疗局部晚期乳腺癌的临床疗效和安全性。方法:选取2010年3月~2012年8月在我院接受治疗的局部晚期乳腺癌患者80例,以其中采用紫杉醇联合卡铂治疗的40例患者作为实验组,紫杉醇联合表阿霉素治疗的40例患者作为对照组,化疗后患者行乳腺癌改良根治术或保乳术,观察和比较两组患者的治疗有效率、不良反应的发生情况及术后复发和转移情况。结果:两组患者的治疗有效率及不良反应的发生率比较均并无统计学差异(P>0.05),而实验组患者术后复发及转移的发生率明显低于对照组患者(P<0.05)。结论:紫杉醇联合卡铂治疗局部晚期乳腺癌的临床疗效及安全性与紫杉醇联合表阿霉素化疗相当,但是能够明显降低患者的术后复发率及转移率,改善患者的预后。     

Effects of insecticides on life history parameters of the aphid parasitoidAphidius rhopalosiphi [Hym.: Aphidiidae]

The effects of four insecticides (two organophosphates, a pyrethroid and a carbamate), applied at different dosages, on different life history parameters of the aphid parasitoidAphidius rhopalosiphi (De Stefani-Perez) were tested. The methods used simulated field conditions in the laboratory. After application on the mummies, only two treatments (parathion and the high dosage of pirimicarb) caused a significant reduction of adult hatching. Fertility and longevity of the wasps were not affected by any of the tested insecticides. Dried residues of parathion, but not of the other insecticides, killed a considerable number ofA. rhopalosiphi females. The searching behaviour of the wasps was affected by demeton-S-methyl and fenvalerate. A direct application of demeton-S-methyl, parathion, and the high dosage of pirimicarb onA. rhopalosiphi females caused high mortality.     

ES细胞（MESPU13）嵌合体小鼠的GPI分析

为了评判小鼠ＥＳ细胞系ＭＥＳＰＵ１３的分化潜能,我们对１９只嵌合小鼠的心、肝、脾、肺、肾、胰腺、生殖腺、肌肉和血液的ＧＰＩ（磷酸葡萄糖异构酶）进行了分析。在这些样品中,来源于ＥＳ细胞的Ａ型条带的检出情况和小鼠的毛色嵌合率成正比关系。当毛色嵌合率低于４０％时,除了少数小鼠的肾脏外,没有看到Ａ型的条带。当毛色嵌合率大于８５％时,几乎所有的器官组织都检测到Ａ型条带,显示了ＥＳ细胞在发育形成内、中、外胚层的细胞方面具有很高的分化潜能。另外,在毛色嵌合率大于８５％的其中的６只嵌合鼠的肌肉中,只观察到Ａ型的条带,表明这些肌肉只单独来源于ＥＳ细胞。     

MTP-PE in liposomes as a biological response modifier in the treatment of cancer: Current status

MTP-PE in liposomes is a BRM which can be given relatively safely to patients with cancer. The maximum tolerated dose appears to be higher than the optimal dose inducing immunomodulatory effects such as cytokine induction and monocyte/macrophage activation. The most consistently induced cytokines measured in the plasma of patients a few hours after MTP-PE are TNF and IL-6. Indirect evidence supports the assumption that increased levels of TNF and IL-6 are signs of macrophage activation occurringin situ in tissues taking up liposomal MTP-PE shortly after injection. These tissues are mainly lungs, liver and spleen, as shown in 4 patients injected with radiolabelled liposomes containing MTP-PE. Assuming that activated monocytes and macrophages cannot eliminate gross tumor load, the main targets for MTP-PE are micrometastases after removal of the primary tumor. Thus, adjuvant treatment using liposomal MTP-PE in combination with chemotherapy is a major goal for the future.     

The impact of two insecticides on predatory ground beetles (Carabidae) in newly-sown grass

Field scale experiments carried out over three years showed that chlorpyrifos reduced the numbers of several carabid beetle species caught in pitfall traps. Fonofos seed treatment was also shown to affect selected species. Consideration of the biology of individuals of groups of species provided explanations of why some species such as Nebria brevicollis, Notiophilus spp., Bembidion spp., and Trechus quadristriatus were severely affected by one or other of the chemicals, whereas other species (e.g. Amara spp., Harpalus spp.) were able to survive or recolonise pastures shortly after chemical application. Measurements of elytral and pronotal widths and counts of mature eggs in N. brevicollis, which was trapped in reduced numbers over a long period, were made and provided some information about the mode of action of these chemicals.     

Physiological susceptibility of the predator Macrolophus basicornis (Hemiptera: Miridae) to pesticides used to control of Tuta absoluta (Lepidoptera: Gelechiidae)

In order to aid the integration of biological and chemical controls for the tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), this study evaluated the relative toxicity of five insecticides to the leaf miner predator Macrolophus basicornis (Stal) (Hemiptera: Miridae). The insecticides evaluated were teflubenzuron, abamectin, chlorantraniliprole, chlorfenapyr, and cartap hydrochloride, all of which are recommended for control of T. absoluta in Brazil. Nymphs and adults of M. basicornis were exposed to tomato leaves treated with the insecticides, under laboratory and greenhouse conditions. The overall mortality caused by the products in both situations was recorded, and the survival of congeneric groups was analysed using the Weibull model. The persistence of the insecticides was also evaluated and they were categorised into toxicity classes proposed by the International Organisation for Biological Control (IOBC) based on predator mortality and persistence. Abamectin and chlorfenapyr were toxic to M. basicornis nymphs and adults in all bioassays. Cartap hydrochloride was slightly harmful to adults in laboratory assays, but harmful to nymphs, and moderately harmful under greenhouse conditions. Chlorantraniliprole and teflubenzuron were harmless in most assays, except when nymphs were exposed in the laboratory, where they were moderately and slightly harmful, respectively. Chlorantraniliprole and teflubenzuron should be preferred insecticides for use in tomato leaf miner IPM programmes that aim to conserve M. basicornis populations.     

Life Cycle of Isospora rivolta (Grassi, 1879) in Cats and Mice*

SYNOPSIS. The endogenous development of Isospora rivolta (Grassi) was studied in cats fed oocysts, and was compared with the endogenous cycle after feeding them mice infected with I. rivolta. For the mouse-induced cycle, 14 newborn cats were killed 12 to 240 h after having been fed mesenteric lymph nodes and spleens of mice. Asexual and sexual development occurred throughout the small intestine, in epithelial cells of the villi and glands of Lieberkuhn. The number of asexual generations was not determined with certainty, but there were at least 3 structurally different meronts. Type I meronts appeared at 12–48 h postinoculation (HPI). They were 8.5(6–13) × 5.1(3–6) μm, contained 2–8 merozoites, and divide by binary division or endodyogeny. Type II meronts were multinucleate merozoite-shaped meronts within a single parasitophorous vacuole. They were found at 48–172 HPI and measured 12.6(9–18) × 9.8(9–13) μm. Individual multinucleate merozoite-shaped meronts were 7–13 × 3–5 μm in sections and contained 2–30 slender (5.5 × 1.0 μm) merozoites. Type III meronts occurred at 72–192 HPI and gamonts at 72–96 HPI. Mature microgamonts measured 11.3(9–15) × 8.0(6–9) μm in sections and up to 21.5 × 14 μm in smears, and contained up to 70 microgametes. Macrogamonts measured 13.3(11–18) × 9.0(5–13) μm in sections and 18 × 16 μm in smears. Oocysts were 10–15 × 9–15 μm in sections and 19.8(17–24) × 18.0(17–23) μm in fixed and stained smears. Unsporulated oocysts in feces were 22.3(18–25) × 19.7(16–23) μm and spomlated oocysts 25.4(23–29) × 23.4(20–26) μm. Sporulation was completed within 24 h at 22–26 C. For the study of the oocyst-induced cycle in cats, 18 newborn cats were killed between 6 and 192 HPI. The endogenous development was essentially similar to the mouse-induced cycle, but merogony and gametogony occurred 12–48 h later than in the latter cycle. Isospora rivolta was pathogenic for newborn but not for weaned cats. Newborn cats fed 10⁵ sporocysts or infected mice usually developed diarrhea 3–4 days after inoculation. Microscopically, desquamation of the tips of the villi and cryptitis were seen in the ilium and cecum in association with meronts and gamonts. For the study of the development of I. rivolta in mice, mice were killed from day 1 to 23 months after having been fed 10⁵–10⁵ sporocysts, and their tissues were examined for the parasites microscopically, and by feeding to cats. The following conclusions were drawn. (A) Isospora rivolta most frequently invaded the mesenteric lymph nodes of mice and remained there for 23 months at least. It also invaded the spleen, liver, and skeletal muscles of mice. This species could not be passed from mouse to mouse. Sporozoites increased in size from ?6.8 × 4.9 μm on day 1 to ?13.4 × 6.9 μm on day 31 postinoculation. Division was not seen. Prepatent period was 4–7 days and patent periods ranged from 2 to several weeks.     

烧伤膏对小鼠皮肤烫伤创面愈合的修复作用研究

目的:探讨烧伤膏对烫伤小鼠皮肤创面修复的可能作用机制。方法:将50只小鼠随机分为5组:正常组、模型组,烧伤膏高、中、低剂量组。除正常组和模型组外,烧伤膏实验组小鼠每天外涂烧伤膏治疗,连用15天。治疗结束后,采用Masson染色技术检测各组小鼠皮肤厚度及细胞病理形态;采用生化法检测皮肤中羟脯氨酸(Hyp)含量;采用ELISA技术检测皮肤中的TNF-α,IL-1β、Collagen I、EGF和TGF-β1的含量。结果:与正常组相比,模型组小鼠皮肤烫伤创面可见表皮细胞脱落,结构模糊,细胞变性坏死,表皮和真皮厚度明显减少,胶原纤维变薄,排列紊乱无序,呈断裂状;烧伤后创面局部组织中Hyp、TNF-α、IL-1β的含量显著升高(P0.01,P0.01,P0.01),而EGF、TGF-β1和Collagen I含量均明显减少(P0.01,P0.01,P0.01),而应用烧伤膏治疗15天后,上述各项实验指标明显得到改善。结论:烧伤膏抑制创面早期感染,减少胶原蛋白的分解和促进后期创面修复的作用可能与抑制炎性细胞因子和增加皮肤相关生长因子表达的作用机制有关。     

Enhanced Aspartate Release Related to Epilepsy in (EL) Mice

Abstract: Previous studies have shown that potassium-evoked, calcium-dependent, endogenous aspartate release is greater from hippocampal slices of adult epileptic (EL) mice than from nonepileptic control C57BL/6J (B6) mice. To examine further the association between epilepsy and enhanced aspartate release in EL mice, endogenous neurotransmitter release from hippocampal slices was studied in young, seizure-free EL mice and in two nonseizure control mouse strains, DDY and B6. DDY is the parental strain from which EL arose, and it has a genetic background similar to EL. Released amino acid neurotransmitters were quantitated by HPLC with fluorescent detection and were expressed as picomoles of amino acid released per minute of incubation per slice ± SEM. Aspartate release was significantly higher in EL mice (15.8 ± 0.8) than in either the control B6 or DDY mice (8.5 ± 1.4 and 8.4 ± 1.7, respectively). No significant differences were found among the B6, DDY, and EL mice for the release of glutamate (23.0 ± 2.0, 32.3 ± 5.8, and 25.9 ± 2.6, respectively) or GABA (23.5 ± 0.7, 19.5 ± 3.2, and 21.8 ± 3.2, respectively). Thus, enhanced aspartate release precedes the onset of EL seizures and may be related to the cause rather than to the effects of seizure activity.     

小鼠骨髓内皮细胞条件培养液复合FL及TPO对HPP—CFC及CFU—GM增殖的影响

通过传代培养小鼠骨髓内皮细胞,收集无血清条件培养液（ECM）,并经超滤得到大于10kD的浓缩液,分别观察ECM和大于10kD的浓缩液复合flt3ligand(FL)及thrombopoietin(TPO)对体外培养HPP-CFC、CFU-GM的影响,结果表明：ECM或大于10kD的浓缩液对HPP-CFC、CFU-GM的生长均有支持作用;FL或/和TPO与ECM或大于10kD的浓缩液合用能加强对HPP-CFC、CFU-GM生长的刺激作用;FL加TPO与ECM或大于10kD的浓缩液合用对HPP-CFC、CFU-GM生长的刺激作用更加明显;选择FL和TPO特异性的引物,用RT-PCR技术未能检测到小鼠骨髓内皮细胞有FL和TPOmRNA的表达。