Royal Postgraduate Medical School

London, United Kingdom

Royal Postgraduate Medical School

London, United Kingdom

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Walters M.C.,Childrens Hospital | Hardy K.,Childrens Hospital | Edwards S.,Childrens Hospital | Adamkiewicz T.,Emory University | And 20 more authors.
Biology of Blood and Marrow Transplantation | Year: 2010

We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease. © 2010 American Society for Blood and Marrow Transplantation.


PubMed | UK National Institute for Medical Research and Royal Postgraduate Medical School
Type: Journal Article | Journal: Immunology today | Year: 2014

There is considerable evidence that, in vivo, C3 is required for the induction and maintenance of memory cells of the B-cell lineage. Recent data from in-vitro systems indicate that ligation of C3 receptors on B cells can activate these cells, and that appropriately presented C3 split products can act as B-cell growth factors. Here, Gerry Klaus and John Humphrey propose that in vivo these growth-promoting effects of C3 may operate within the microenvironment of germinal centres, where B cells encounter antigen-antibody-C3 complexes on the surfaces of follicular dendritic cells.


PubMed | Royal Postgraduate Medical School
Type: Journal Article | Journal: Leukemia & lymphoma | Year: 2010

Splenectomy specimens from 8 cases of chronic lymphocytic leukaemia (CLL) were examined. The infiltrate in the red pulp consisted predominantly of small lymphocytes. In contrast the predominant cells in the white pulp were pro-lymphocytes and para-immunoblasts. The Ki67 marker, which identifies cells in growth phase, was also concentrated among the transformed cells in the white pulp. Staining with monoclonal antibodies for CD21, which identifies the CR2 receptor, showed that the cells in the white pulp were strongly positive in contrast to those in the red pulp which were weak or negative. These findings suggest that factors present in the white pulp promote transformation and proliferation of CLL cells.


PubMed | Royal Postgraduate Medical School
Type: Journal Article | Journal: Fish physiology and biochemistry | Year: 2013

The current state of knowledge about regulatory peptides in endocrine cells and nerves of the alimentary canal of lampreys and hagfishes is reviewed. Cyclostomes have a wide range of peptides similar immunochemically to those of higher vertebrates. They include, in the endocrine cells of the intestine, peptides resembling glucagon, gastrin/cholecystokinin, peptide YY (pancreatic polypeptide/neuropeptide Y), substance P, vasoactive intestinal peptide, somatostatin and, in the larval stages at least, insulin. The enteric nerves of some lamprey species contain peptides resembling bombesin (gastrin-releasing peptide) and calcitonin gene-related peptide, as well as serotonin. The occurrence of other peptides is less well documented.Little is known of the molecular structure or the biological roles of the enteric peptides in cyclostomes. Extraction, purification, sequencing and physiological experiments are greatly needed.


PubMed | Royal Postgraduate Medical School
Type: Journal Article | Journal: Biochemical pharmacology | Year: 2010

Human and rat liver microsomal fractions exhibit non-linear Michaelis-Menten kinetics in the O-deethylation of both phenacetin and 7-ethoxycoumarin. Comparison of various models indicated that the data were best described by a biphasic plot, which could be interpreted in terms of two populations of cytochrome P-450. The K(m)s of the high affinity phase of 7-ethoxycoumarin O-deethylase activity were 1.8 +/- 0.4 microM and 2.3 +/- 0.4 microM for human and rat respectively while the K(m)s of the low affinity phase were 205 +/- 20 microM and 237 +/- 59 microM in the two species respectively. V(max) of the high affinity phase of human 7-ethoxycoumarin O-deethylase activity was 96.9 +/- 19.0 pmol mg(-1) min(-1) and the activity of the corresponding phase in the rat was 2.7 times greater. The activities of the low affinity phase were 10-15 times greater than the respective activity of the high affinity phase. Rat and human also had similar values for the K(m)s of the two phases of phenacetin O-deethylase activity, around 5 microM for the high affinity phase and 300 microM for the low affinity phase. Total activity was very similar in the two species, 1500-1750 pmol mg(-1) min(-1) and the difference between the two phases of activity was only 2.5-fold in man and 10-fold in rat. Studies on the effects of the in vitro modifiers of monooxygenase activity alpha-naphthoflavone and metyrapone further supported the hypothesis that the two phases of O-deethylase activity represent two different forms or populations of cytochrome P-450.

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