Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

The prognosis of rectal carcinoid tumours

Carcinoid tumours of the rectum are very rare, and they may present sprecial therapeutic problems for the surgeon. Tumour size and muscle layer invasion are the two most important factors predicting their malignant potential. A series of 20 patients with carcinoid tumours of the rectum were reviewed. 16 tumours less than 2 cm in diameter had neither muscle layer invasion nor lymph node metastases, with the exception of one tumour. Four patients with tumours larger than 2 cm died from metastatic carcinoid. In order to plan operative management endoluminal ultrasound should be performed preoperatively. Rectal carcinoid tumours should be treated like carcinomas of the rectum if they are 2 cm or more in diameter or if they demonstrate muscularis propria invasion independent of tumour size.

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Résumé Les tumeurs carcinoïdes du rectum sont très rares et peuvent présenter des problèmes thérapeutiques particuliers pour le chirurgien. Le calibre de la tumeur et l'invasion des couches musculaires sont les deux facteurs les plus importants pour prévoir leur potentiel malin. Une série de 20 malades présentant une tumeur carcinoïde du rectum a été revue. Les 16 tumeurs de moins de 2 cm de diamètre ne présentaient ni invasion des couches musculaires, ni métastase lymphatique à l'exception d'une seule. 4 patients avec des tumeurs plus grandes que 2 cm sont morts de métastases carcinoïdes. En vue de planifier la conduite opératoire l'échographie endo-rectale devrait être pratiquée pré-opératoirement. Les tumeurs carcinoïde du rectum devraient être traitées comme des cancers du rectum si leur diamètre dépasse 2 cm où si elles démontrent une invasion de la musculaire propre, indépendamment de la taille de la tumeur.

     

Immunocytochemical detection of p21 ras expression in fresh human leukaemic cells and cell lines

Summary The expression of p21 ^ras proteins was investigated by immunocytochemistry in permanent cell lines and in fresh human leukaemic cells. While high and low levels of p21 ^ras could be detected in most of the cell lines, no significant p21 ^ras immunoreactivity was noted in cells of ten human acute and chronic leukaemias. Thus, notwithstanding its possible role in the initial transformation process in human leukaemias, p21 ^ras expression appears not to be an irrevocable requirement for the maintenance of the transformed state.     

Motion artifacts in MRI: A complex problem with many partial solutions

Subject motion during magnetic resonance imaging (MRI) has been problematic since its introduction as a clinical imaging modality. While sensitivity to particle motion or blood flow can be used to provide useful image contrast, bulk motion presents a considerable problem in the majority of clinical applications. It is one of the most frequent sources of artifacts. Over 30 years of research have produced numerous methods to mitigate or correct for motion artifacts, but no single method can be applied in all imaging situations. Instead, a “toolbox” of methods exists, where each tool is suitable for some tasks, but not for others. This article reviews the origins of motion artifacts and presents current mitigation and correction methods. In some imaging situations, the currently available motion correction tools are highly effective; in other cases, appropriate tools still need to be developed. It seems likely that this multifaceted approach will be what eventually solves the motion sensitivity problem in MRI, rather than a single solution that is effective in all situations. This review places a strong emphasis on explaining the physics behind the occurrence of such artifacts, with the aim of aiding artifact detection and mitigation in particular clinical situations. J. Magn. Reson. Imaging 2015;42:887–901.     

Adapted Personalized Cognitive Counseling for Episodic Substance-Using Men Who Have Sex with Men: A Randomized Controlled Trial

Episodic drug use and binge drinking are associated with HIV risk among substance-using men who have sex with men (SUMSM), yet no evidence-based interventions exist for these men. We adapted personalized cognitive counseling (PCC) to address self-justifications for high-risk sex among HIV-negative, episodic SUMSM, then randomized men to PCC (n = 162) with HIV testing or control (n = 164) with HIV testing alone. No significant between-group differences were found in the three primary study outcomes: number of unprotected anal intercourse events (UAI), number of UAI partners, and UAI with three most recent non-primary partners. In a planned subgroup analysis of non-substance dependent men, there were significant reductions in UAI with most recent non-primary partners among PCC participants (RR = 0.56; 95 %CI 0.34–0.92; P = 0.02). We did not find evidence that PCC reduced sexual risk behaviors overall, but observed significant reductions in UAI events among non-dependent SUMSM. PCC may be beneficial among SUMSM screening negative for substance dependence.     

Opposing roles of membrane and soluble forms of the receptor for advanced glycation end products in primary respiratory syncytial virus infection

Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager(-/-)) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager(-/-) mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager(-/-) mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection.