Noninvasive Assessment by Doppler and M-Mode Echocardiography of Hemodynamic Responses to Temporary Pacing and to Ventriculoatrial Conduction

A new, dual-chamber temporary pacing lead was introduced via the subclavian vein in 20 patients who needed a temporary pacemaker. Stroke volume (SV) was measured continuously by combining M-mode and noninvasive Doppier echocardiography during spontaneous rhythm (SR), AV sequential pacing at a positive AV interval (DP), ventricular pacing (VP) and AV sequential pacing at a negative AV interval (VA pacing). The valvular functions were determined by Doppler echocardiography. Left ventricular dimensions and function, and left atrial size were measured by M-mode echocardiography. In the nine patients with no valvular heart disease and with no ventriculoatrial (VA) conduction (group I) the CO increased 83 ±11% during DP and 42 ± 9% during VP as compared to during SR when the heart rate (HE) was increased from 34 ± 3 to 72 ± 1 beats/min. The CO was 29 ± 3% higher during DP than that during VP. In the seven patients with valvulox heart disease and with no VA conduction (group II), the increment in CO compared to that during Sfi was SZ ± 12% during DP and 31 ±17% during VP: the CO was 17 ± 4% higher during DP than that during VP. In the four patients with spontaneous VA conduction (group III), the CO during DP was 35 ± 10% greater than that during VP, which did not result in an increase in the CO compared to that during SR in spile of an increase in HR from 52 ± 8 to 74 ± 2 beats/min. The study demonstrated that DP is the preferred temporary pacing mode and also that VA conduction during VP resulted in a mean decrease of 20% in CO compared to that during VP without VA conduction. The hemodynamic benefit from DP compared to SR seems to decrease when the left ventricular end-diastolic dimension increases. Furthermore, patients with large left ventricular end-systolic dimensions seem to have a lower increase in stroke index during DP as compared to that during VP than patients with smaller end-systolic dimensions.     

Disease-modifying capability of murine Flt3-ligand DCs in experimental autoimmune encephalomyelitis

Dendritic cells (DCs) bridge the innate and adaptive immune response, are uniquely capable of priming na?ve T cells, and play a critical role in the initiation and regulation of autoimmune and immune-mediated disease. At present, in vivo expansion of DC populations is accomplished primarily through the administration of the recombinant human growth factor fms-like tyrosine kinase 3 ligand (hFL), and in vitro DCs are generated using cytokine cocktails containing GM-CSF +/- IL-4. Although hFL has traditionally been used in mice, differences in amino acid sequence and biological activity exist between murine FL (mFL) and hFL, and resultant DC populations differ in phenotype and immunoregulatory functional capabilities. This study developed and characterized mFL-generated DCs and determined the therapeutic capability of mFL DCs in the autoimmune disease experimental autoimmune encephalomyelitis (EAE). Our findings demonstrate that mFL and hFL expand splenic DCs equally in vivo but that mFL-expanded, splenic DCs more closely resemble normal, resting, splenic DCs. In addition, a novel method for generating mFL-derived bone marrow-derived DCs (BM-DCs) was developed, and comparison of mFL with hFL BM-DCs found mFL BM-DCs to be less mature (i.e., lower MHC Class II, CD80, and CD86) than hFL BM-DCs. These immature mFL DCs up-regulated costimulatory molecules in response to maturation stimuli LPS and TNF-alpha. Mature mFL BM-DCs were immunogenic and exacerbated the clinical disease course of EAE.     

妊娠期妇女高危型人乳头瘤病毒感染与宫颈病变的相关性研究

目的探讨妊娠期妇女高危型人乳头瘤病毒(HR-HPV)感染与宫颈病变的相关性。方法选取重庆华西妇产医院就诊的18~43岁妊娠期妇女486例,行第二代分子杂交捕获技术(HC2-HPV-DNA)和超微病原体可视检测技术(TH)2种方法联合检测及电子阴道镜下病理活检,以病理活检结果为诊断宫颈病变的金标准。结果 486例妊娠期妇女HR-HPV检测阳性患者161例,阳性率33.12%(161/486);病理组织学诊断出宫颈癌(ICC)及癌前病变(CIN)24例;HPV阳性患者的宫颈癌及癌前病变22例,敏感性91.67%(22/24)。HR-HPV感染情况在不同年龄段分布,差异有统计学意义(P0.05),HR-HPV病毒载量及阳性表达率越高,宫颈病变的程度越高。结论妊娠期妇女不同年龄段的HR-HPV感染率不同;HR-HPV阳病毒载量与CIN及ICC发生有关,与宫颈病变的发生过程有关,但与宫颈病变的严重程度无关;妊娠期妇女HPV感染的宫颈病变阳性率和病毒载量与非妊娠期妇女相似;HC2-HPV-DNA法是目前筛查癌前病变及宫颈癌的最佳方法。     

P38MAPK信号转导通路与血管细胞增殖及缺血再灌注的关系

丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)是广泛表达的丝氨酸/酪氨酸激酶,在真核生物细胞多种信号转导通路中起重要的作用,受多种因素的调控,作用底物多种多样。P38信号通路是MAPK通路中相当重要的一个分支,在炎症、细胞应激、凋亡、细胞周期和生长等多种生理、病理过程中起着重要作用。     

Neuroendocrine modulation of chronic relapsing experimental autoimmune encephalomyelitis: a critical role for the hypothalamic-pituitary-adrenal axis

Murine relapsing EAE can be profoundly suppressed by restraint stress (RST) administered beginning prior to neuroantigen immunization. This study determined what hormone pathway(s) mediate disease suppression. Our results showed that nadolol (NAD), a β₂-adrenergic antagonist, did not reverse the RST-induced suppression of EAE. However, administration of either RU486 or aminoglutethimide, which block the action of peripheral glucocorticoids, resulted in a partial reversal of EAE suppression. Administration of exogenous corticosterone mimicked the effects of RST, in terms of suppression of EAE, decrease in lymphoid cell numbers and decrease in Th1 cytokine production. Therefore, the HPA axis plays a more profound role in the RST-induced suppression of EAE than does the sympathetic nervous system.     

Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone secretion in women with polycystic ovarian syndrome

The suppression of the pituitary-gonadal axis by the administration of gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an adjunct therapy with gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS). A number of recent clinical studies have suggested that women with polycystic ovaries (PCO) may have disturbances of normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth factor (IGF)-I system. The purpose of this study was to determine the effect of GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in women with PCOS. Eight women with PCO and six control women were studied before and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg monthly injections). GHRH was given as a single i.v. injection and blood samples for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min. The GH responses were expressed as the area under the curve (AUC) or the differences from the basal value (delta(max)). The GH response to GHRH (mean +/- SEM) was lower in women with PCO (AUC 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min, P < 0.05 and delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml, P < 0.05). After treatment with the GnRH-a, the GH response to GHRH was significantly smaller than before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller response. These data demonstrate that women with PCO have a reduced GH response to GHRH compared with normal controls and that GnRH-a administration causes a further GH reduction in both groups. Women with PCO have a greater suppression of GH response to GHRH during treatment with GnRH-a. This suggests that a different level of sensitivity in the somatotrophic axis exists in PCOS.      

Differential chemokine response of murine macrophages stimulated with cytokines and infected with Listeria monocytogenes

During inflammatory processes the infected macrophage is a rich source of chemokines which induce infiltration of leukocytes to the site of infection. We investigated the regulation of chemokine production by murine macrophages in response to infection with the intracellular bacterial pathogen, Listeria monocytogenes. As a source of quiescent macrophages, murine bone marrow-derived macrophages (BMM) cultured under serum-free conditions were used. With RT-PCR, we detected induction of RNA message for the chemokines macrophage inflammatory protein (MIP)-2, KC, MIP-1alpha, MIP-1beta, IFN-gamma-inducible protein- 10 and RANTES in L. monocytogenes-infected macrophages. Accordingly, ELISA-detectable MIP-1alpha, MIP-2 and KC protein was induced by infection with L. monocytogenes. In contrast, L. monocytogenes infection of BMM alone failed to induce considerable expression of monocyte chemoattractant protein (MCP)-1 at the mRNA or protein level, but co-treatment with IFN-gamma was necessary. Release of infection- triggered MIP-2, MIP-1alpha and KC was negatively regulated by IFN- gamma. Similarly, IL-4 stimulated MCP-1 release by infected macrophages but reduced production of MIP-1alpha, MIP-2 and KC. IL-10 turned out to be a general deactivator in terms of macrophage chemokine production. IL-13 had no effect on MIP-1alpha, MIP-2 and KC production by infected BMM, but slightly reduced MCP-1 release. By using IFN-gamma and IL-4 gene deletion mutant mice, in vivo regulation of these chemokines by IL- 4 and IFN-gamma in listeriosis was studied. In summary, our results show that chemokines are produced by macrophages infected with L. monocytogenes, and that chemokine release is differentially regulated by the macrophage modulators IFN-gamma, IL-4, IL-10 and IL-13.      

Effects of IL-13 on murine listeriosis

Acquired resistance against Listeria monocytogenes is a typical T helper (Th) 1 dominated immune response, whereas Th2 cytokines are thought to worsen listeriosis. We investigated effects of recombinant IL-13 (rIL-13) on the host response to L. monocytogenes in mice. Although IL-13 has been described as a Th2 cytokine with deactivating anti-inflammatory activities, it was found to enhance antilisterial resistance. In vitro, rIL-13 increased IL-12 p40 and p70 production by bone marrow macrophages infected with L. monocytogenes. In vivo, numbers of viable bacteria in spleens and livers were decreased after treatment of mice with rIL-13. In addition, granuloma formation was impaired and NK cell activity of spleen cells was enhanced. At the onset of infection, frequencies of IL-12-producing cells were increased and numbers of IL-4- and IFN-gamma-secreting cells were diminished in rIL-13-treated mice as compared to controls. In contrast, on day 6 after infection, IL-12, IL-4 and IFN-gamma levels in rIL-13-treated animals were equal to or even higher than those in controls. Although direct activation of host macrophages by IL-13 is possible, we consider it more likely that IL-13 acted indirectly through stimulation of IL-12 production and inhibition of IL-4 release early after infection. In contrast, our data argue against an apparent role of IFN-gamma in IL-13- induced antilisterial resistance.