Morphological evolution of the mammalian cecum and cecal appendix

The evolutionary pressures leading to the appearance of the cecal appendix, its evolutionary relationships with the cecum, and the link between these gastrointestinal characters and ecology remain controversial. We collected data on appendix presence and size, other gastrointestinal characters, ecological variables, dietary habits, and social characters hypothesized to drive appendix evolution for 533 mammalian species. Using phylogeny-informed analyses, we identified the first evidence of a positive correlation between appendix presence and cecal apex thickness, and a correlation with cecal morphology, suggesting that the appendix and cecum may be evolving as a module, the cecoappendicular complex. A correlation between appendix presence and concentration of cecal lymphoid tissue supports the hypothesis of an adaptive immune function for this complex. Other new findings include an inverse correlation between relative cecum length and habitat breadth, and positive relationships between cecum length and mean group size, and between colon length and weaning age.     

Structural requirements of 5-hydroxytryptamine-moduline analogues to interact with the 5-hydroxytryptamine1B receptor

Using magnetic resonance methods and a clinically relevant rodent model of sepsis, we have made in vivo measurements of increased intracellular calcium in a pathologic state in the CNS. The intracellular calcium concentration was increased nearly twofold in septic rat brain compared with controls (p < 0.0001). This result, in a fully intact functioning mammalian system, ties together a previous spectrum of indirect evidence from numerous laboratories suggesting an important role for elevated intracellular calcium in sepsis. In addition, levels of the proinflammatory cytokine tumor necrosis factor-a were elevated threefold in septic rat brain (p < 0.02), and electron microscopic examination revealed scattered injury in approximately 0.25% of glial cells. These findings are discussed in light of the current understanding of the pathophysiology of sepsis.     

京尼平对脓毒血症小鼠T细胞的免疫调节作用及其潜在机制

目的:探究京尼平对脓毒血症小鼠T细胞的免疫调节作用及其潜在机制。方法:小鼠盲肠结扎穿孔手术(CLP)后,分别在0h和24 h尾静脉注射1 mg/kg、2.5 mg/kg、5 mg/kg京尼平和磷酸盐缓冲液(PBS),连续7d观察和记录小鼠的死亡数。另取小鼠分为Sham组(n=8)、Genipin组(n=8)、CLP组(n=8)、Genipin+CLP组(n=14),Sham组注射PBS并实施假手术,Genipin组注射2.5 mg/kg京尼平并实施假手术,CLP组注射PBS并实施手术,Genipin+CLP组注射2.5 mg/kg京尼平并实施手术。CLP手术26 h后收集脾脏,检测脾脏淋巴细胞总数、CD4~+、CD8~+、细胞因子和凋亡蛋白FADD、caspase-3、caspase-8表达水平。结果:给药2.5 mg/kg的京尼平小鼠存活率高于其他小鼠。CLP组小鼠脾脏淋巴细胞总数、CD4~+、CD8~+、白介素(IL)-2、干扰素(IFN)-γ水平低于Sham组,CLP+Genipin组小鼠上述指标高于CLP组(P0.05);CLP组小鼠凋亡蛋白FADD、caspase-3、caspase-8表达、IL-4、IL-10水平高于Sham组,CLP+Genipin组小鼠上述指标低于CLP组(P0.05)。结论:京尼平能够通过抑制T细胞凋亡改善脓毒血症后期的免疫抑制,提高脓毒性小鼠的存活率。     

Role of nitric oxide in the expression of hepatic vascular stress genes in response to sepsis

This study examined the role of nitric oxide (NO) on the expression of the hepatic vasoregulatory gene during polymicrobial sepsis. Aminoguanidine (AG, 100 mg/kg) or Nomega-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) was injected intraperitoneally at 0, 3, 6, 10, and 20 h after a cecal ligation and puncture (CLP). The heart rate increased 24 h after the CLP, and this increase was attenuated by L-NAME and further attenuated by AG. The mean arterial pressure in the CLP animals did not change significantly 24 h after the onset of sepsis but was increased after the L-NAME injection. Sepsis increased the serum aminotransferase levels, which were attenuated by AG but augmented by L-NAME. CLP increased the mRNA level of the ET-1 and ETB receptors in the liver. This increase was prevented by AG but augmented by L-NAME. The level of iNOS and HO-1 mRNA expression were increased by CLP, which was prevented by both AG and L-NAME. The level of TNF-alpha and COX-2 mRNA expression increased after CLP, and was attenuated by AG. These results show that iNOS and eNOS are regulated differently in sepsis. While eNOS appears to have a protective role in liver microcirculation, the strong upregulation of iNOS might contribute to a microvascular dysfunction and hepatic injury.     

The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock

Neuromedin U (NMU) is a neuropeptide involved in appetite, circadian rhythm, and pronociception. However, the NMU receptor NMU-R1 has been shown to be expressed in immune cells and NMU promotes mast cell-dependent inflammation. In this study, we demonstrated that NMU plays an important role in IL-6 production in macrophages. NMU-deficient mice were resistant against cecal ligation puncture- as well as LPS-induced septic shock. IL-6 but not TNF-alpha levels were markedly reduced in LPS-treated NMU-deficient mice compared with wild type mice. Both NMU and NMU-R1 were expressed in wild type peritoneal macrophages, and treatment with LPS resulted in up-regulation of NMU but down-regulation of NMU-R1 expression, however, no down-regulation of NMU-R1 was observed in NMU-deficient macrophages where LPS-induced IL-6 production was severely reduced. These data suggest that LPS-induced IL-6 expression is partly dependent on autocrine/paracrine activation of the NMU-NMU-R1 signals in macrophages.     

Comparative anatomy and phylogenetic distribution of the mammalian cecal appendix

A recently improved understanding of gut immunity has merged with current thinking in biological and medical science, pointing to an apparent function of the mammalian cecal appendix as a safe‐house for symbiotic gut microbes, preserving the flora during times of gastrointestinal infection in societies without modern medicine. This function is potentially a selective force for the evolution and maintenance of the appendix, and provides an impetus for reassessment of the evolution of the appendix. A comparative anatomical approach reveals three apparent morphotypes of the cecal appendix, as well as appendix‐like structures in some species that lack a true cecal appendix. Cladistic analyses indicate that the appendix has evolved independently at least twice (at least once in diprotodont marsupials and at least once in Euarchontoglires), shows a highly significant (P < 0.0001) phylogenetic signal in its distribution, and has been maintained in mammalian evolution for 80 million years or longer.     

注水式结肠镜检查法的研究进展

注水式结肠镜检查法是指用注水代替传统的注气,通过向肠腔内注水以扩张肠管,循腔进镜的肠镜检查方法。自1984年《新英格兰杂志》首次报道应用传统的注气式结肠镜检查失败时,应用辅助注水的方式帮助寻找肠腔走行,有利于内镜顺利通过憩室段以来,经过三十年的发展与研究,注水式结肠镜检查法较传统的注气式结肠镜检查具有减轻患者腹痛、缩短进镜时间及提高盲肠插管成功率等方面的优势。本文主要就注水式结肠镜检查法的历史起源、发展历程、研究进展、存在的问题以及应用前景等进行了综述。     

Using stable isotopes and C:N ratios to examine the life‐history strategies and nutritional sources of larval lampreys

Natural abundance stable‐isotope analysis (δ¹³C and δ¹⁵N) and C:N ratios were used to study the ammocoete phase of two common non‐parasitic lamprey species (least brook lamprey Lampetra aepyptera and American brook lamprey Lethenteron appendix) in two tributaries of the Ohio River (U.S.A.). The C:N ratios suggest that each species employs different lipid accumulation strategies to support its metamorphosis and recruitment into an adult animal. Ammocoete δ¹³C values generally increased with increasing C:N values. In contrast to δ¹³C, ammocoete δ¹⁵N values were weakly related to the total length (L_T) in L. aepyptera, but positively correlated to both L_T and C:N ratios in L. appendix. In L. appendix, C:N also correlated positively with L_T, and presumably age. A Bayesian mixing model using δ¹³C and δ¹⁵N was used to estimate nutritional subsidies of different potential food resources to ammocoetes at each site. The models suggested that although nutritional subsidies to ammocoetes varied as a function of site, ammocoetes were generally reliant on large contributions (42–62% at three sites) from aquatic plants. Contributions from aquatic sediment organic matter were also important at all sites (32–63%) for ammocoetes, with terrestrially derived plant materials contributing smaller amounts (4‐33%). These findings provide important insights into the feeding ecology and nutrition of two species of lampreys. They also suggest that similar and other quantitative approaches are required to (1) fully understand how the observed stable‐isotopes ratios are established in ammocoetes and (2) better assess ammocoete nutritional subsidies in different natal streams.     

High RAD51 mRNA levels in young rabbit appendix. A role in B-cell gene conversion?

 The rabbit has a limited number of V _H genes that rearrange. As in the chicken, the 3′-most V _H 1 gene is rearranged in most B lymphocytes. This laboratory reported that by 6 weeks after birth, diversification of rearranged V _H genes occurs, at least in part, by gene conversion-like events in the appendix, suggesting that this organ is a homologue of the avian bursa of Fabricius. Rad51 contributes to the repair of double-strand breaks in DNA during somatic and meiotic recombination. The gene was first identified in lower eukaryotes, and later in vertebrates including chicken, as encoding an Escherichia coli RecA-like protein. We report the cloning and sequencing of RAD51 from the rabbit. Because the chicken bursa was shown to express high levels of RAD51 message, we investigated the expression of RAD51 in the rabbit appendix and other tissues. Using a quantitative polymerase chain reaction mimic assay and conventional northern analyses, we found high RAD51 expression in young rabbit appendix comparable to levels in testis where there is an abundance of meiotic recombination. RAD51 levels were three times higher in appendix B lymphocytes compared with T lymphocytes and were lower in adult appendix, as well as in spleen and Peyer's patches of young rabbits. We measured the levels of message in several appendix cell sub-populations obtained by fluorescence-activated cell sorting and found that sub-populations of B lymphocytes corresponding to different stages of B-cell development as well as B cells undergoing isotype switch did not have significantly different mRNA levels. Received: 18 October 1997 / Revised: 10 December 1997