Roger Pool - Academia.edu (original) (raw)

Papers by Roger Pool

Journal of Hematopathology, 2015

High-grade non-Hodgkin's lymphomas with plasmablastic differentiation are frequently encountered ... more High-grade non-Hodgkin's lymphomas with plasmablastic differentiation are frequently encountered in HIV-positive patients. Differentiating between diffuse large B cell lymphoma (DLBCL) with plasmablastic differentiation and true cases of plasmablastic lymphoma (PBL) is sometimes challenging, particularly as a substantial overlap in immunphenotype exists between late-stage B cell neoplasms and PBL. This study sought to develop an immunohistochemical panel to more reliably distinguishing between PBL and DLBCL with plasmablastic differentiation. Thirty-nine CD20negative, ALK-negative, HHV8-negative non-Hodgkin's lymphomas with plasmablastic differentiation defined by their morphological features, high proliferation index and positivity for MUM1/IRF4 and PRDM/Blimp1 protein expression were compared regarding their protein expression profiles, viral status and c-MYC-gene aberrations. These lymphomas were subsequently divided in two groups utilising CD10 and Pax5. Tumours without reactivity for either of these markers exhibited higher expression of CD138 and CD117 frequently used as the plasma cell (PC) markers, whilst tumours with reactivity for one or both markers showed a significantly higher expression of CD38 and MYC-gene aberrations. A novel diagnostic scoring system which includes the immunohistochemical expression of CD10 and Pax5 is proposed to differentiate between DLBCL with plasmablastic differentiation and true cases of PBL.

The human innate immune system is indispensable for protection against potentially invasive micro... more The human innate immune system is indispensable for protection against potentially invasive microbial and
viral pathogens, either neutralising them or containing their spread until effective mobilisation of the slower,
adaptive (specific), immune response. Until fairly recently, it was believed that the human innate immune
system possessed minimal discriminatory activity in the setting of a rather limited range of microbicidal or
virucidal mechanisms. However, recent discoveries have revealed that the innate immune system possesses
an array of novel pathogen recognition mechanisms, as well as a resourceful and effective alternative
mechanism of phagocyte (predominantly neutrophil)-mediated, anti-infective activity known as NETosis.
The process of NETosis involves an unusual type of programmed, purposeful cell death, resulting in the
extracellular release of a web of chromatin heavily impregnated with antimicrobial proteins. These structures,
known as neutrophil extracellular traps (NETs), immobilise and contribute to the eradication of microbial
pathogens, ensuring that the anti-infective potential of neutrophils is sustained beyond the lifespan of these
cells. The current review is focused on the mechanisms of NETosis and the role of this process in host
defence. Other topics reviewed include the potential threats to human health posed by poorly controlled,
excessive formation of NETs, specifically in relation to development of autoimmune and cardiovascular
diseases, as well as exacerbation of acute and chronic inflammatory disorders of the airways.

European Respiratory Journal, 2015

South African journal of child health

British Journal of Haematology, 2003

A two-year-old black African boy was referred to Ga-Rankuwa Hospital with generalized lymphadenop... more A two-year-old black African boy was referred to Ga-Rankuwa Hospital with generalized lymphadenopathy, hepatomegaly and multiple non-tender swellings over the head. A whole-body isotope [meta-iodobenzylguanidine (MIBG)] scan (left) was performed, which demonstrated a large primary tumour in the region of the left adrenal gland together with extensive skeletal metastases. A MIBG scan images the adrenal medulla and sympathetic nervous tissue, and these results, therefore, suggested metastatic neuroblastoma.

British Journal of General Practice, 2011

The primary objective of the current study was to investigate the potential of the pneumococcal t... more The primary objective of the current study was to investigate the potential
of the pneumococcal toxin, pneumolysin (Ply), to activate neutrophil
extracellular trap (NET) formation in vitro. Isolated human blood
neutrophils were exposed to recombinant Ply (5-20 ng ml21) for 30–90 min
at 378C and NET formation measured using the following procedures to
detect extracellular DNA: (i) flow cytometry using VybrantVR DyeCycleTM
Ruby; (ii) spectrofluorimetry using the fluorophore, SytoxVR Orange (5 lM);
and (iii) NanoDropVR technology. These procedures were complemented
by fluorescence microscopy using 40, 6-diamino-2-phenylindole (DAPI)
(nuclear stain) in combination with anti-citrullinated histone monoclonal
antibodies to visualize nets. Exposure of neutrophils to Ply resulted in
relatively rapid (detected within 30–60 min), statistically significant
(P < 005) dose- and time-related increases in the release of cellular DNA
impregnated with both citrullinated histone and myeloperoxidase.
Microscopy revealed that NETosis appeared to be restricted to a
subpopulation of neutrophils, the numbers of NET-forming cells in the
control and Ply-treated systems (10 and 20 ng ml21) were 43 (42), 14.3
(99) and 165 (75), respectively (n 5 4, P < 00001 for comparison of the
control with both Ply-treated systems). Ply-induced NETosis occurred in the
setting of retention of cell viability, and apparent lack of involvement of
reactive oxygen species and Toll-like receptor 4. In conclusion, Ply induces
vital NETosis in human neutrophils, a process which may either contribute
to host defence or worsen disease severity, depending on the intensity of the
inflammatory response during pneumococcal infection.

Journal of Hematopathology, 2015

High-grade non-Hodgkin's lymphomas with plasmablastic differentiation are frequently encountered ... more High-grade non-Hodgkin's lymphomas with plasmablastic differentiation are frequently encountered in HIV-positive patients. Differentiating between diffuse large B cell lymphoma (DLBCL) with plasmablastic differentiation and true cases of plasmablastic lymphoma (PBL) is sometimes challenging, particularly as a substantial overlap in immunphenotype exists between late-stage B cell neoplasms and PBL. This study sought to develop an immunohistochemical panel to more reliably distinguishing between PBL and DLBCL with plasmablastic differentiation. Thirty-nine CD20negative, ALK-negative, HHV8-negative non-Hodgkin's lymphomas with plasmablastic differentiation defined by their morphological features, high proliferation index and positivity for MUM1/IRF4 and PRDM/Blimp1 protein expression were compared regarding their protein expression profiles, viral status and c-MYC-gene aberrations. These lymphomas were subsequently divided in two groups utilising CD10 and Pax5. Tumours without reactivity for either of these markers exhibited higher expression of CD138 and CD117 frequently used as the plasma cell (PC) markers, whilst tumours with reactivity for one or both markers showed a significantly higher expression of CD38 and MYC-gene aberrations. A novel diagnostic scoring system which includes the immunohistochemical expression of CD10 and Pax5 is proposed to differentiate between DLBCL with plasmablastic differentiation and true cases of PBL.

The human innate immune system is indispensable for protection against potentially invasive micro... more The human innate immune system is indispensable for protection against potentially invasive microbial and
viral pathogens, either neutralising them or containing their spread until effective mobilisation of the slower,
adaptive (specific), immune response. Until fairly recently, it was believed that the human innate immune
system possessed minimal discriminatory activity in the setting of a rather limited range of microbicidal or
virucidal mechanisms. However, recent discoveries have revealed that the innate immune system possesses
an array of novel pathogen recognition mechanisms, as well as a resourceful and effective alternative
mechanism of phagocyte (predominantly neutrophil)-mediated, anti-infective activity known as NETosis.
The process of NETosis involves an unusual type of programmed, purposeful cell death, resulting in the
extracellular release of a web of chromatin heavily impregnated with antimicrobial proteins. These structures,
known as neutrophil extracellular traps (NETs), immobilise and contribute to the eradication of microbial
pathogens, ensuring that the anti-infective potential of neutrophils is sustained beyond the lifespan of these
cells. The current review is focused on the mechanisms of NETosis and the role of this process in host
defence. Other topics reviewed include the potential threats to human health posed by poorly controlled,
excessive formation of NETs, specifically in relation to development of autoimmune and cardiovascular
diseases, as well as exacerbation of acute and chronic inflammatory disorders of the airways.

European Respiratory Journal, 2015

South African journal of child health

British Journal of Haematology, 2003

A two-year-old black African boy was referred to Ga-Rankuwa Hospital with generalized lymphadenop... more A two-year-old black African boy was referred to Ga-Rankuwa Hospital with generalized lymphadenopathy, hepatomegaly and multiple non-tender swellings over the head. A whole-body isotope [meta-iodobenzylguanidine (MIBG)] scan (left) was performed, which demonstrated a large primary tumour in the region of the left adrenal gland together with extensive skeletal metastases. A MIBG scan images the adrenal medulla and sympathetic nervous tissue, and these results, therefore, suggested metastatic neuroblastoma.

British Journal of General Practice, 2011

The primary objective of the current study was to investigate the potential of the pneumococcal t... more The primary objective of the current study was to investigate the potential
of the pneumococcal toxin, pneumolysin (Ply), to activate neutrophil
extracellular trap (NET) formation in vitro. Isolated human blood
neutrophils were exposed to recombinant Ply (5-20 ng ml21) for 30–90 min
at 378C and NET formation measured using the following procedures to
detect extracellular DNA: (i) flow cytometry using VybrantVR DyeCycleTM
Ruby; (ii) spectrofluorimetry using the fluorophore, SytoxVR Orange (5 lM);
and (iii) NanoDropVR technology. These procedures were complemented
by fluorescence microscopy using 40, 6-diamino-2-phenylindole (DAPI)
(nuclear stain) in combination with anti-citrullinated histone monoclonal
antibodies to visualize nets. Exposure of neutrophils to Ply resulted in
relatively rapid (detected within 30–60 min), statistically significant
(P < 005) dose- and time-related increases in the release of cellular DNA
impregnated with both citrullinated histone and myeloperoxidase.
Microscopy revealed that NETosis appeared to be restricted to a
subpopulation of neutrophils, the numbers of NET-forming cells in the
control and Ply-treated systems (10 and 20 ng ml21) were 43 (42), 14.3
(99) and 165 (75), respectively (n 5 4, P < 00001 for comparison of the
control with both Ply-treated systems). Ply-induced NETosis occurred in the
setting of retention of cell viability, and apparent lack of involvement of
reactive oxygen species and Toll-like receptor 4. In conclusion, Ply induces
vital NETosis in human neutrophils, a process which may either contribute
to host defence or worsen disease severity, depending on the intensity of the
inflammatory response during pneumococcal infection.