腺病毒载体介导的PML生长抑制因子对前列腺癌细胞生长和致瘤能力的抑制效果

为探讨用腺病毒载体携带ＰＭＬ（ＰｒｏｍｙｅｌｏｃｙｔｉｃＬｅｕｋｅｍｉａ）基因作为前列腺癌基因治疗的可能性，应用重组人携带ＰＭＬ基因腺病毒（ＡｄＰＭＬ）感染培养的前列腺癌细胞，观察表达ＰＭＬ蛋白的癌细胞与对照组癌细胞的体外生长和裸鼠体内致瘤能力变化，对荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ，观察治疗组和对照组肿瘤生长的变化。结果显示，感染ＡｄＰＭＬ的前列腺癌细胞体外生长和裸鼠体内致瘤能力明显下降，荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ后肿瘤生长速度明显减慢。证实了ＰＭＬ是一种生长抑制因子，提示其可能被应用于前列腺癌的基因治疗研究     

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

Lymph node infarction – a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever

Background  

Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature.     

Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin

The integrin alpha4beta7 binds to MAdCAM-1 and contributes to homing of lymphocytes to gut and other mucosal tissues. In humans, the alpha4beta7(hi) subset of circulating memory cells appears to have been primed in mucosal tissues. The factors that determine whether alpha4beta7(lo) naive cells become alpha4beta(hi) or alpha4beta7(-) cells upon differentiation are poorly understood but could include an influence of the activating antigen-presenting cell. To address this point, the induction of alpha4beta7 following activation of mouse cells with the APC-dependent stimulus soluble anti-CD3 has been examined. Almost all mouse T cells freshly isolated from mesenteric lymph nodes (MLN) and peripheral (PLN; axillary, brachial and inguinal) lymph nodes stained only weakly for alpha4beta7 but a subpopulation became alpha4beta7(hi) upon activation with anti-CD3 in a cell cycle- and accessory cell-dependent manner. A small proportion (approximately 1.5 %) of the starting cells gave rise to alpha4beta7(hi) cells after culture. A higher proportion of alpha4beta7(hi) cells were generated in MLN than PLN cultures. Peyer's patch cultures gave intermediate values. In crossover experiments, MLN dendritic cells (DC) induced higher proportions and numbers of alpha4beta7(hi) cells than PLN DC irrespective of the source of T cells. Therefore, in addition to their other immunoregulatory roles, DC have the potential to shape immune responses by influencing the homing of the lymphocytes they activate.     

Bladder pheochromocytoma encountered on sonography

Pheochromocytomas of the bladder are rare neoplasms, constituting <0.06% of all vesical tumours. Common presenting features of this tumour include episodes of sweating, hypertension, haematuria and postmicturition syncope. We describe a case of bladder pheochromocytoma in a 66‐year‐old man whose only symptom of macroscopic haematuria was initially assessed with ultrasonography. Clinical presentation highlights the need for a high index of suspicion during sonographic evaluation of bladder neoplasms because such tumours might present without symptoms of adrenergic excess.     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.     

Acute coronary syndromes

The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or ‘primary’ percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.