St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

A Study of the Nuclear Apparatus of Bacteria

Abstract: Dumbbell-shaped bodies giving a positive Feulgen reaction and possessing a strong affinity for nuclear dyes have been observed in resting bacterial spores and vegetative cells from young cultures. A special study was made of the resting and germinating spores of two strains of Bacillus mycoides . Resting spores contain one chromatinic dumbbell body, closely attached to, but distinct from, a rod of non- chromatinic protoplasm. Division forms of this body occur in a few spores. When germination begins, the dumbbell body enters the rod of protoplasm , where it soon becomes invisible. When it reappears at a later stage of the germination process, it has divided into two closely contiguous dumbbell bodies. Further divisions of the chromatinic bodies precede the divisions of the vegetative cells in a regular way. Each vegetative cell usually contains a pair of dumbbell bodies. Similar chromatinic bodies have been demonstrated in the cells of Proteus vulgaris and two Sarcinae. The two single Feulgen-positive bodies described by previous authors in the resting cells of various spore-forming and non-sporing organisms thus appear to consist of two pairs of dumbbell bodies, separated by a delicate boundary. The single ‘cells’ to which these writers refer are in fact short, two-celled filaments. It is concluded that the dumbbell bodies are comparable to the chromosomes of plant and animal cells.

The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia.

Abstract: The incidence of bronchopulmonary dysplasia (BPD) among ventilated infants is estimated to be between 4 and 40% depending on gestation but undoubtedly the highest incidence, in excess of 70%, occurs in infants weighing 1000 g or less at birth.' The incidence of BPD may further increase in the coming decade as advances in neonatal intensive care enable clinicians to save even smaller, lower gestation, and more critically ill infants. BPD is already a major cause of mortality and long term morbidity. A significant proportion of infants will be oxygen dependent for a prolonged period of time. Growth delay and neurodevelopmental deficit have also been reported with increasing frequency.' Thus, effective therapeutic measures are urgently required. Dexamethasone, a potent, long acting steroid with almost exclusive glucocorticoid property, was intensively studied and appeared promising in improving pulmonary function. This article examines the efficacy and adverse effects of dexamethasone treatment in preterm infants with BPD.

A p55 TNF Receptor Immunoadhesin Prevents T Cell-Mediated Intestinal Injury by Inhibiting Matrix Metalloproteinase Production

Abstract: Anti-TNF-alpha Ab therapy has been shown to be of benefit in the treatment of active Crohn's disease, but the tissue-injuring processes in the gut mediated by TNF-alpha that might be inhibited by neutralizing Ab are unknown. In this work, we have used a p55 TNF receptor-human IgG fusion protein (TNFR-IgG) to prevent the severe mucosal injury that ensues when lamina propria T cells in explant cultures of human fetal small intestine are directly activated with the lectin PWM. Following T cell activation and associated with mucosal injury, there is a marked elevation of soluble TNF-alpha in organ culture supernatants and a large increase in TNF-alpha mRNA transcripts. The addition of TNFR-IgG at the onset of cultures greatly reduced PWM-induced tissue injury, without inhibiting the increase in TNF-alpha and IFN-gamma transcripts seen following T cell activation. Mucosal injury in this model is mediated by endogenously-produced matrix metalloproteinases (MMPs). When TNFR-IgG was added to PWM-stimulated explants, there was a reduction in MMPs in the explant culture supernatants, especially stromelysin-1. Recombinant TNF-alpha and IL-1beta added directly to mucosal mesenchymal cell lines also caused an increase in MMP production, but only the former was inhibited by the TNFR-IgG. These results suggest that one of the ways in which TNF-alpha causes tissue injury in the gut is by stimulating mucosal mesenchymal cell to secrete matrix-degrading metalloproteinases. Neutralization of this activity should help maintain tissue integrity.

Leukocyte transmigration, but not rolling or adhesion, is selectively inhibited by dexamethasone in the hamster post-capillary venule. Involvement of endogenous lipocortin 1.

Abstract: This study investigates the effect of dexamethasone on leukocyte extravasation in the post-capillary venules of the hamster cheek pouch, using an intravital microscopy technique, and seeks to clarify the potential involvement of the steroid-inducible protein lipocortin 1. Topical application of FMLP (10 nmol), or substance P (10 nmol), to the superfused cheek pouch induced at the level of the post-capillary venules the three characteristic phenomena of leukocyte rolling, adhesion, and transmigration. Pretreatment of hamsters with an anti-inflammatory dose of dexamethasone (1 mg/kg) increased lipocortin 1 levels in circulating leukocytes as assessed by flow cytometry, but did not modify either leukocyte rolling or the number of adherent cells; however approximately 65% of the adherent leukocytes subsequently detached and returned to the blood stream, whereas those that entered into the diapedesis process exhibited a long latency (approximately three- to fourfold longer than in control animals) before transmigration. In hamsters passively immunized with a polyclonal anti-lipocortin 1 serum, leukocyte diapedesis started at similar times in both control and dexamethasone-treated animals, whereas a significant prolongation was observed in those animals treated with a non-immune sheep serum. These observations indicate that 1) lipocortin 1 is elevated in circulating leukocytes following dexamethasone treatment; 2) the step of leukocyte extravasation affected by dexamethasone in the actual transmigration process, and 3) this specific effect upon leukocyte diapedesis is mediated by endogenous lipocortin 1.

Targeting the FMS-like tyrosine kinase 3 in acute myeloid leukemia

Abstract: Acute myeloid leukemia (AML) is a highly heterogenous disease with multiple signaling pathways contributing to its pathogenesis. A key driver of AML is the FMS-like tyrosine kinase receptor-3 (FLT3). Activating mutations in FLT3, primarily the FLT3-internal tandem duplication (FLT3-ITD), are associated with decreased progression-free and overall survival. Identification of the importance of FLT3-ITD and the FLT3 pathway in the prognosis of patients with AML has stimulated efforts to develop therapeutic inhibitors of FLT3. Although these inhibitors have shown promising antileukemic activity, they have had limited efficacy to date as single agents and may require use in combination with cytotoxic chemotherapies. Here, we review clinical and preclinical results for the clinically mature FLT3 inhibitors currently in development. We conclude that multitargeted FLT3 inhibitors may have more utility earlier in the course of disease, when in vitro evidence suggests that AML cells are less dependent on FLT3 signaling, perhaps because of upregulation of multiple other signaling pathways. More potent agents may have greater utility in relapsed and heavily pretreated patients, in whom high levels of circulating FLT3 ligand may necessitate use of an agent with a very favorable pharmacokinetic/pharmacodynamic profile. Novel combination regimens are also discussed.