Jon Geske - Academia.edu (original) (raw)

Papers by Jon Geske

Cell Death & Differentiation, Feb 1, 2001

Virology Journal, 2010

BackgroundLassa fever is a neglected tropical disease with significant impact on the health care ... more BackgroundLassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV)-like particle (VLP)-based modular vaccine ...

The American Journal of Pathology, 2001

Apoptosis is a type of cell death that has specific morphological, biochemical, and regulatory ch... more Apoptosis is a type of cell death that has specific morphological, biochemical, and regulatory characteristics, somehow different from necrosis. 1 It was described in our time by the Australian pathologist John Kerr 2,3 and given its present name by Kerr et al in 1972. 4 It is interesting that this type of cell death was also described by Glucksman in 1951 as present in normal embryological development. 5 We found recently that the famous German pathologist and biologist Rudolf Virchow (1821-1902) described apoptosis in a lecture given in 1858. 6 In it, he described two types of cell death, necrobiosis versus necrosis. The former is "always here to deal with a gradual decay and death, a dissolution.. .. Necrobiosis is death brought on by (altered) life, a spontaneous wearing out of living parts, the destruction and annihilation consequent on life, natural as opposed to violent death (mortification).. .. But the idea of necrosis really does not offer any analogy to these processes.. . ." In summary, we should add to Virchow's accomplishments the early suggestion of apoptosis, which he called necrobiosis and which, he made very clear, was different from necrosis.

International Journal of Laboratory Hematology, 2012

YN, JN, MA, and FJG have been or are employed at Precision BioLogic, manufacturer of the VWF:CB a... more YN, JN, MA, and FJG have been or are employed at Precision BioLogic, manufacturer of the VWF:CB assay components. EJF was an employee of Sydney West Area Health Service (SWAHS) at the time of this study; SWAHS was financially remunerated for consulting services provided by EJF to Precision BioLogic, including the analysis of data presented in this manuscript.

Chemical & Engineering News

animal feeds animal hair, hoofs, etc. bark bones corn cobs cotton crab shells feathers felt ferti... more animal feeds animal hair, hoofs, etc. bark bones corn cobs cotton crab shells feathers felt fertilizers fish bones foam rubber gelatin glass fiber grain hay lead scrap leather paper plastics rayon roots seeds shellac spaghetti teeth tin foil titanium scrap tobacco wood pulp etc., etc.

Journal of Mammary Gland Biology and Neoplasia, May 1, 2002

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as... more The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoetic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.

Method Cell Biol, 1995

ABSTRACT

Molecular diagnosis & therapy, 2008

Journal of mammary gland biology and neoplasia, 2002

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as... more The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoietic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.

Methods in Cell Biology, 1995

ABSTRACT

Methods in Cell Biology, 1995

ABSTRACT

PLoS Neglected Tropical Diseases, 2014

Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is... more Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings: Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the postconflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

Molecular Diagnosis & Therapy, 2008

Lupus, 2010

Since β2-glycoprotein I (β2GPI) was described as the major antigenic target for antiphospholipid ... more Since β2-glycoprotein I (β2GPI) was described as the major antigenic target for antiphospholipid antibodies, many studies have focused their attention to the physiological role of β2GPI and anti-β2GPI antibodies on autoimmune-mediated thrombosis. Studies reporting the physiological role of β2GPI have been numerous, but the exact mechanism of action(s) has yet to be completely determined. β2GPI’s epitopes for anti-β2GPI autoantibodies have been characterized, however, not all of the heterogeneous anti-β2GPI antibodies are pathogenic. The pathophysiologic role of β2GPI has been reported in the fields of coagulation, fibrinolysis, angiogenesis, and atherosclerosis. Our understanding of the impact of β2GPI, its metabolites and autoantibodies to β2GPI on these physiological functions may contribute to the development of better therapeutic strategies to treat and prevent autoimmune-mediated atherothrombotic vascular disease. Lupus (2010) 19, 379—384.

Journal of Vascular Surgery, 2009

International Journal of Hematology, 2002

Clearance of cellular corpses is a critical feature of apoptosis in vivo during development, tiss... more Clearance of cellular corpses is a critical feature of apoptosis in vivo during development, tissue homeostasis, and resolution of inflammation. As the professional phagocytes of the body, macrophages play a key role in this process. By recognizing emerging signals using several different receptors, macrophages engulf apoptotic cells swiftly and efficiently. In addition, the binding of apoptotic cells profoundly down-regulates the ability of the macrophage to produce inflammatory mediators by inducing the release of antiinflammatory mediators. Finally, macrophages may actually induce cell death in specific cells during embryogenesis. Abnormalities of apoptotic cell clearance may contribute to the pathogenesis of chronic inflammatory diseases, including those of autoimmune etiology. It is also possible that certain malignant tumor cells co-opt the mechanisms for apoptotic cell clearance to avoid immune surveillance by subverting macrophage and dendritic cell responses.

Journal of mammary gland …, 2002

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as... more The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoetic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.

Cell Death & Differentiation, Feb 1, 2001

Virology Journal, 2010

BackgroundLassa fever is a neglected tropical disease with significant impact on the health care ... more BackgroundLassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV)-like particle (VLP)-based modular vaccine ...

The American Journal of Pathology, 2001

Apoptosis is a type of cell death that has specific morphological, biochemical, and regulatory ch... more Apoptosis is a type of cell death that has specific morphological, biochemical, and regulatory characteristics, somehow different from necrosis. 1 It was described in our time by the Australian pathologist John Kerr 2,3 and given its present name by Kerr et al in 1972. 4 It is interesting that this type of cell death was also described by Glucksman in 1951 as present in normal embryological development. 5 We found recently that the famous German pathologist and biologist Rudolf Virchow (1821-1902) described apoptosis in a lecture given in 1858. 6 In it, he described two types of cell death, necrobiosis versus necrosis. The former is "always here to deal with a gradual decay and death, a dissolution.. .. Necrobiosis is death brought on by (altered) life, a spontaneous wearing out of living parts, the destruction and annihilation consequent on life, natural as opposed to violent death (mortification).. .. But the idea of necrosis really does not offer any analogy to these processes.. . ." In summary, we should add to Virchow's accomplishments the early suggestion of apoptosis, which he called necrobiosis and which, he made very clear, was different from necrosis.

International Journal of Laboratory Hematology, 2012

YN, JN, MA, and FJG have been or are employed at Precision BioLogic, manufacturer of the VWF:CB a... more YN, JN, MA, and FJG have been or are employed at Precision BioLogic, manufacturer of the VWF:CB assay components. EJF was an employee of Sydney West Area Health Service (SWAHS) at the time of this study; SWAHS was financially remunerated for consulting services provided by EJF to Precision BioLogic, including the analysis of data presented in this manuscript.

Chemical & Engineering News

animal feeds animal hair, hoofs, etc. bark bones corn cobs cotton crab shells feathers felt ferti... more animal feeds animal hair, hoofs, etc. bark bones corn cobs cotton crab shells feathers felt fertilizers fish bones foam rubber gelatin glass fiber grain hay lead scrap leather paper plastics rayon roots seeds shellac spaghetti teeth tin foil titanium scrap tobacco wood pulp etc., etc.

Journal of Mammary Gland Biology and Neoplasia, May 1, 2002

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as... more The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoetic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.

Method Cell Biol, 1995

ABSTRACT

Molecular diagnosis & therapy, 2008

Journal of mammary gland biology and neoplasia, 2002

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as... more The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoietic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.

Methods in Cell Biology, 1995

ABSTRACT

Methods in Cell Biology, 1995

ABSTRACT

PLoS Neglected Tropical Diseases, 2014

Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is... more Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings: Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the postconflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

Molecular Diagnosis & Therapy, 2008

Lupus, 2010

Since β2-glycoprotein I (β2GPI) was described as the major antigenic target for antiphospholipid ... more Since β2-glycoprotein I (β2GPI) was described as the major antigenic target for antiphospholipid antibodies, many studies have focused their attention to the physiological role of β2GPI and anti-β2GPI antibodies on autoimmune-mediated thrombosis. Studies reporting the physiological role of β2GPI have been numerous, but the exact mechanism of action(s) has yet to be completely determined. β2GPI’s epitopes for anti-β2GPI autoantibodies have been characterized, however, not all of the heterogeneous anti-β2GPI antibodies are pathogenic. The pathophysiologic role of β2GPI has been reported in the fields of coagulation, fibrinolysis, angiogenesis, and atherosclerosis. Our understanding of the impact of β2GPI, its metabolites and autoantibodies to β2GPI on these physiological functions may contribute to the development of better therapeutic strategies to treat and prevent autoimmune-mediated atherothrombotic vascular disease. Lupus (2010) 19, 379—384.

Journal of Vascular Surgery, 2009

International Journal of Hematology, 2002

Clearance of cellular corpses is a critical feature of apoptosis in vivo during development, tiss... more Clearance of cellular corpses is a critical feature of apoptosis in vivo during development, tissue homeostasis, and resolution of inflammation. As the professional phagocytes of the body, macrophages play a key role in this process. By recognizing emerging signals using several different receptors, macrophages engulf apoptotic cells swiftly and efficiently. In addition, the binding of apoptotic cells profoundly down-regulates the ability of the macrophage to produce inflammatory mediators by inducing the release of antiinflammatory mediators. Finally, macrophages may actually induce cell death in specific cells during embryogenesis. Abnormalities of apoptotic cell clearance may contribute to the pathogenesis of chronic inflammatory diseases, including those of autoimmune etiology. It is also possible that certain malignant tumor cells co-opt the mechanisms for apoptotic cell clearance to avoid immune surveillance by subverting macrophage and dendritic cell responses.

Journal of mammary gland …, 2002

The processes by which the involuting mammary gland clears residual milk and milk fat, as well as... more The processes by which the involuting mammary gland clears residual milk and milk fat, as well as apoptotic cells, have gone largely unstudied in the modern literature. Here we review the evidence for and against the involvement of professional phagocytes of hematopoetic lineage in this process. Additionally we present evidence that mammary epithelial cells themselves are capable of phagocytosis and may be responsible for the majority of apoptotic cell and residual milk clearance during murine involution. In this scheme these cells regulate their cytokine production in response to apoptotic cells in a manner similar to other cells, including macrophages. The ensuing model describes a process of involution that actively suppresses an inflammatory response in the gland, allowing for effective tissue remodeling and damage prevention.