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S Majeed

Publications and source records attributed to S Majeed.

9 recordsLinked to original sources
PubMed2002

The death-inducing signalling complex is recruited to lipid rafts in Fas-induced apoptosis.

Membrane microdomains known as lipid rafts have been shown recently to be involved in Fas signalling and apoptosis in T and B cell lines. Here, we have investigated further the role of lipid rafts in Fas-induced apoptosis in non-transformed human CD4 T cells. We show that Fas-induced apoptosis in CD4 T cells was inhibited by the lipid raft disrupter methyl-beta-cyclodextrin. When lipid rafts were isolated from control and Fas ligand treated cells, we found that a small proportion of Fas was present in the raft fraction in untreated cells and that this was greatly increased upon Fas ligation. The other components of the Death Inducing Signalling Complex (DISC), FADD, and procaspase 8, were also present at higher levels in the raft fraction isolated from Fas ligand treated cells. We conclude that formation of the DISC occurs in lipid rafts and that these membrane microdomains are required for efficient Fas signalling and apoptosis.

Apoptosis↗
PubMed2000

Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates.

BACKGROUND: The gp120 exterior envelope glycoprotein of HIV-1 binds sequentially to CD4 and chemokine receptors on cells to initiate virus entry. During natural infection, gp120 is a primary target of the humoral immune response, and it has evolved to resist antibody-mediated neutralization. We previously reported the structure at 2.5 A of a gp120 core from the HXBc2 laboratory-adapted isolate in complex with a 2 domain fragment of CD4 and the antigen binding fragment of a human antibody. This revealed atomic details of gp120-receptor interactions and suggested multiple mechanisms of immune evasion. RESULTS: We have now extended the HXBc2 structure in P222, crystals to 2.2 A. The enhanced resolution enabled a more accurate modeling of less-well-ordered regions and provided conclusive identification of the density in the central cavity at the crux of the gp120-CD4 interaction as isopropanol from the crystallization medium. We have also determined the structure of a gp120 core from the primary clinical HIV-1 isolate, YU2, in the same ternary complex but in a C2 crystal lattice. Comparisons of HXBc2 and YU2 showed that while CD4 binding was rigid, portions of the gp120 core were conformationally flexible; overall differences were minor, with sequence changes concentrated on a surface expected to be exposed on the envelope oligomer. CONCLUSIONS: Despite dramatic antigenic differences between primary and laboratory-adapted HIV-1, the gp120 cores from these isolates are remarkably similar. Taken together with chimeric substitution and sequence analysis, this indicates that neutralization resistance is specified by quaternary interactions involving the major variable loops and thus affords a mechanism for viral adaptation. Conservation of the central cavity suggests the possibility of therapeutic inhibitors. The structures reported here extend in detail and generality our understanding of the biology of the gp120 envelope glycoprotein.

Amino Acid Sequence↗
PubMed2000

Refractory priapism of unknown etiology in a pediatric patient.

Priapism is a urologic emergency that can occur in any age group and every patient should receive prompt urologic consultation. Management of priapism is based on the recognition of underlying pathophysiology; ready differentiation between high-flow and low-flow priapism; reversal of any potential precipitating factors; the use of corporal aspiration irrigation combined with intracavernosal alpha adrenergic therapy; and when necessary, a shunting procedure. Delay in recognition or treatment can be crucial as the incidence of long-term complication rises substantially with the duration of the priapism.

Adolescent↗
PubMed1978

Ultrastructural study of mesenteric lymph nodes in old rats.

The large mononuclear cells showed the features of mononuclear phagocytes and were mainly characterised by a large number of vacuolar structures. The results suggest that there is storage of lipids and mucosubstances, probably in enlarged lysosomes.

Aging↗
PubMed1978

Histochemical study of mesenteric lymph nodes in old rats.

The main positive reactions in the large mononuclear cell occurring in some nodes were shown with PAS, alcian blue, Sudan black B and acid haematin. The results suggest that in these cells, considered to be mononuclear phagocytes, there is a storage of hexose-containing mucosubstances, acid mucopolysaccharides and choline-containing phospholipids.

Aging↗