Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Building a Methodological Foundation for Impactful Urban Planetary Health Science

Anthropogenic environmental change will heavily impact cities, yet associated health risks will depend significantly on decisions made by urban leaders across a wide range of non-health sectors, including transport, energy, housing, basic urban services, and others. A subset of planetary health researchers focus on understanding the urban health impacts of global environmental change, and how these vary globally and within cities. Such researchers increasingly adopt collaborative transdisciplinary approaches to engage policy-makers, private citizens, and other actors in identifying and evaluating potential policy solutions that will reduce environmental impacts in ways that simultaneously promote health, equity, and/or local economies—in other words, maximising ‘co-benefits’. This report presents observations from a participatory workshop focused on challenges and opportunities for urban planetary health research. The workshop, held at the 16th International Conference on Urban Health (ICUH) in Xiamen, China, in November 2019, brought together 49 participants and covered topics related to collaboration, data, and research impact. It featured research projects funded by the Wellcome Trust’s Our Planet Our Health (OPOH) programme. This report aims to concisely summarise and disseminate participants’ collective contributions to current methodological practice in urban planetary health research.     

Emergency surgery comparison of right versus left acute colonic diverticulitis: A 10-year outcome analysis

IntroductionThe difference in outcome between right (RCD) and left colonic diverticulitis (LCD) is not well established. The aim of this study was to analyse the presentation and surgical outcome of RCD versus left-sided disease following emergency surgery.MethodWe conducted a retrospective review of patients presenting with acute diverticulitis over a 10-year period from 2004 to 2014 to a tertiary unit. Patient demographics, Hinchey classification, need for emergency surgery, perioperative outcome and recurrence were evaluated.ResultsIn total 360 patients presented with acute diverticulitis, 218 (61%) were right-sided and 142 (39%) were left-sided. The mean age (57 yrs vs 68 yrs) and median length of stay (4 days vs 5 days) were significantly less in RCD (p < 0.001). The need for emergency surgery was similar between RCD and LCD (30.7% vs 23.2%, p = 0.12). Sixty-seven (31%) patients with RCD required emergency surgery, 42 (62.7%) of these were based on a presumptive diagnosis of appendicitis and underwent laparoscopic appendicectomy only. Operative morbidity (10.4% vs 51.5%, p < 0.001) and mortality were significantly higher in LCD (1.5% v 15.2%, p = 0.007). Subgroup analysis of non-appendicectomy, RCD patients, showed LCD were more likely to require surgery (11.5% vs 23.2%, p = 0.003). There was no difference in recurrence (p = 0.6).ConclusionRight colonic diverticulitis patients are younger and disease course is more benign compared to LCD. Presentation can be confused with appendicitis without proper imaging. In the rare cases where emergency surgery is required, RCD is associated with a lower operative morbidity and mortality compared to left-sided disease.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

Plasticity of autonomic nerves: Differential effects of long-term guanethidine sympathectomy on the sensory innervation of the rat uterus during maturation

The sensory nerves, containing substance P and calcitonin gene-related peptide, and noradrenaline-containing sympathetic nerves of the rat uterus were analyzed following long-term sympathectomy with guanethidine in prepubertal (four weeks), young adult (eight weeks) and fully adult animals (18 weeks). Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows:

1. (1) long-term guanethidine treatment completely abolished the noradrenergic innervation of the uterine horn and parametrial tissue and markedly reduced the tissue levels of noradrenaline in both regions at the three ages analysed;

2. (2) in the uterine hom guanethidine treatment had no effect on the tissue levels of either calcitonin gene-related peptide or substance P or on the density of calcitonin gene-related peptide-containing nerves, at any of the three ages studied;

3. (3) in the parametrial tissue increased levels of calcitonin gene-related peptide were observed at 8 and 18 weeks of age, together with a significant increase in the density of calcitonin gene-related peptide-containing nerves.

Substance P levels showed a transient increase in this tissue at eight weeks. In conclusion, long-term sympathectomy with guanethidine resulted in an increase in calcitonin gene-related peptide and substance P in sensory nerves in the parametrial tissue, but not in the uterine horn. The changes in the parametrial tissue only occurred after puberty. It is suggested that sensory nerves in the uterine horn may be less responsive to sympathetic denervation since loss of sympathetic nerves occurs as part of a normal physiological process during pregnancy in this region.

Mu opioid receptors are in somatodendritic and axonal compartments of GABAergic neurons in rat hippocampal formation

Activation of mu opioid receptors (MORs) has a net excitatory effect in the hippocampal formation through inhibition of gamma-amino butyric acid (GABA)-containing interneurons. To determine the precise subcellular targets of MOR agonists, immunoreactivity against MOR1 and GABA was examined in single sections of the hippocampal formation prepared for dual-labeling electron microscopy. In both the CA1 region of hippocampus and the dentate gyrus, MOR-like immunoreactivity (-li) was present in neuronal somata, dendrites, axons, and axon terminals, as well as a very few glial processes. Axon terminals with MOR-li formed symmetric synapses with principal cell dendrites and somata. Many MOR-labeled profiles of all types also contained GABA-li, and the vast majority possessed the ultrastructural characteristics of interneurons. Additionally, in the dentate gyrus a very small proportion of granule cell dendrites contained MOR-li. MOR-li, identified using immunogold-silver particles, was often affiliated with the extrasynaptic regions of neuronal plasma membranes, consistent with responsiveness to diffusing endogenous neuropeptide ligands. Semiquantitative analysis of the distribution of MOR-li revealed significantly more "presynaptic" (axons and terminals) than "postsynaptic" (somata and dendrites) labeled profiles in most laminae. We conclude that in addition to previously described somatodendritic MOR-li, a substantial amount of MOR-li in hippocampal formation is presynaptic. Furthermore, MORs are almost exclusively in GABAergic interneurons.     

p75NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles

To localize neurotrophin binding sites within the rat dentate gyrus, the distribution of low-affinity p75 neurotrophin receptor (p75NTR) immunoreactivity (IR) was examined by using antiserum raised against the cytoplasmic domain of the receptor. Semiquantitative electron microscopic examination of p75NTR-labeled sections showed that most p75NTR-labeled profiles were axons and axon terminals (72% from a total of 3,975); p75NTR-IR was observed throughout the extent of these structures and was not limited to the plasmalemmal surface. Axons and axon terminals containing p75NTR-IR were distributed in approximately equal proportions across the hilus, infragranular zone, and the inner, middle, and outer molecular layers; significantly fewer p75NTR-labeled profiles were observed in the granule cell layer. Axon terminals containing p75NTR-IR, which made synapses (296 of 552), formed equal proportions of symmetric and asymmetric synapses, primarily with the shafts and spines of dendrites. The remainder of the p75NTR-labeled terminals apposed unlabeled somata and dendrites without forming synapses in the single sections analyzed. In addition, p75NTR-IR was contained within some astrocytes (17.5% of 3,975) and dendritic shafts (3%) and spines (5%). Within dendritic spines, p75NTR-IR was most often associated with the plasmalemmal surface near postsynaptic densities; in dendritic shafts, p75NTR labeling was associated with microfilaments distant from the plasmalemma. Most p75NTR-labeled dendritic profiles were located in the molecular layer, and some originated from granule cells. Moreover, in some granule cell somata (<1% of 3,975), p75NTR-IR was associated with endosomes. The primary localization of p75NTR-IR to presynaptic structures in the dentate gyrus, presumably arising from medial septal/diagonal band neurons, agrees with previous reports. However, p75NTR-IR within some astrocytes, somata, and dendritic structures suggests that this receptor may also be involved in controlling local neurotrophin levels and possibly modulating the viability of local hippocampal cell populations.     

Needs of disabled children and their families.

In the new NHS those who provide services for disabled children need to measure and demonstrate their effectiveness, but there are no easily available outcome measures for use by child development centres and teams. The development of an alternative approach, using a series of statements of good practice, is described. Parents of children with cerebral palsy were asked to participate in semistructured interviews, to ascertain the value and relevance of these quality statements. Parents were most concerned about the standard of news breaking and early follow up, the sharing of information, and the supply and repair of equipment. The findings were used to modify the quality checklist and it is proposed that this should form the basis of a "charter for disabled children and their families''.