Jacqueline Sawyer - Academia.edu (original) (raw)

Papers by Jacqueline Sawyer

The Lancet, Dec 1, 2015

for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of p... more for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of priority antivenoms from Dec 1, 2015. We are also ready to partner with all interested organisations to address this public health issue before existing technical capacity is lost and yet more lives are needlessly impaired or lost. We declare no competing interests.

Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation

The World Health Organisation develops and promotes international standards for pharmaceutical pr... more The World Health Organisation develops and promotes international standards for pharmaceutical products, in support of efforts to increase access to quality-assured medicines for all, and to safeguard patients from substandard and falsified medicines. The International Pharmacopoeia is a key output of this work. Its focus, processes to establish texts for inclusion or revision, response to COVID-19 and the collaboration with other Pharmacopoeias shall be discussed in this review. Pharmacopoeias provide public standards (written norms as well as physical reference standards), which ensure the quality of medicines by defining the attributes that are essential to their safety and efficacy. They consist of analytical methods to test for the identity, purity and content of pharmaceutical products, together with acceptance criteria to evaluate test results, and information about storage, labelling and production. Pharmacopoeias greatly facilitate the development of multi-source medicines ...

The Lancet, 2010

958 www.thelancet.com Vol 376 September 18, 2010 reason that our report stated the need for exten... more 958 www.thelancet.com Vol 376 September 18, 2010 reason that our report stated the need for extensive genotyping of APOA5 (and related loci) in relation to detailed lipoprotein assessments (such as those based on structural and functional characteristics). Jean Dallongeville and Aline Meirhaeghe suggest that caution should be exercised in interpreting our study because the results might not necessarily indicate a role for hypertriglyceridaemia itself, especially since triglyceride metabolism is modulated by factors such as diabetes, obesity, and smoking. It was due to such considerations that the title and conclusions of our report related to “triglyceride-mediated pathways” rather than to hypertriglyceridaemia. (Our study showed that the APOA5 –1131T>C genotype is not materially correlated to the prevalence of diabetes, obesity, and smoking.) Di Zeng and colleagues describe potential limitations of genetic association studies, including the possibility of confounding by other ge...

Journal of Cell Science, Jul 1, 1986

To evaluate the relative mobilities of cell surface glycoconjugates during myogenesis we have stu... more To evaluate the relative mobilities of cell surface glycoconjugates during myogenesis we have studied the redistribution of fluorescein-conjugated plant lectins on L6 rat myogenic cells. Previous experiments had demonstrated that the receptors for the lectins soybean agglutinin (SBA), wheat germ agglutinin, concanavalin A and Lens culinaris agglutinin all were relatively uniformly distributed on both myoblasts and myotubes, and that SBA receptors were capable of rapid redistribution on myotubes but not myoblasts at 4°C (Sawyer & Akeson, 1983). Here we show that when SBA-labelled myoblasts are incubated at 37°C, or for extended times at 4°C, the lectin aggregates as on myotubes. So it appears that SBA-binding components show a quantitative rather than qualitative change in their mobility during L6 differentiation. In addition, the redistribution of the three other lectins on myoblasts and myotubes was either 4ess prominent (i.e. showing fewer apparent surface clusters) or occurred less rapidly than with SBA. None of these three lectins showed striking differences in mobility between myoblasts and myotubes. Thus, it appears that SBA binds to a subset of surface glycoconjugates that is relatively highly mobile, and that this mobility is specifically enhanced with differentiation.

Health Professions - Clinical (The Ohio State University Denman Undergraduate Research Forum)

Proceedings of the National Academy of Sciences, 2011

Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major effo... more Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreov...

Proceedings of the National Academy of Sciences, 2010

Cervical carcinomas are initiated through a series of well-defined stages that rely on the expres... more Cervical carcinomas are initiated through a series of well-defined stages that rely on the expression of human papillomavirus (HPV) oncogenes. A panel of 100 small hairpin RNAs that target essential kinases in many tumor types was used to study the stepwise appearance of kinase requirements during cervical tumor development. Twenty-six kinases were commonly required in three cell lines derived from frank carcinomas, and each kinase requirement was traced to the specific stage in which the requirement emerged. Six kinases became required following HPV-induced immortalization, and the requirement for two kinases, SGK2 and PAK3, was mapped to the inactivation of p53 in primary human epithelial cells. Loss of the p53 tumor suppressor in other primary epithelial cells also induced dependence on SGK2 and PAK3. Hence, SGK2 and PAK3 provide important cellular functions following p53 inactivation, fulfilling the classical definition of synthetic lethality; loss of p53, SGK2, or PAK3 alone ha...

Proceedings of the National Academy of Sciences, 2008

shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promotin... more shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: ( i ) in repeat experiments using the same cells, ( ii ) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and ( iii ) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this stu...

Proceedings of the National Academy of Sciences, 2008

Functional differences among human cells have been difficult to identify by standard biochemical ... more Functional differences among human cells have been difficult to identify by standard biochemical methods. Loss-of-function shRNA screens provide an unbiased method to compare protein requirements across cell lines. In previous work, we have studied kinase requirements in two settings, either among a panel of cells from numerous tissues or between two cell lines that differ only by the expression of a chosen oncoprotein or tumor suppressor protein. Here we examine the patterns of kinase requirements between two unrelated cells, the cervical carcinoma cell line HeLa and the renal carcinoma cell line 786-O. By using time courses of cell proliferation after shRNA transduction and by introducing different levels of the shRNAs, we were able to carefully compare the kinase requirements. These comparisons identified 10 kinases that were required in HeLa but not 786-O, and 5 kinases that were required in 786-O but not HeLa. The patterns of growth inhibition due to particular sets of shRNAs i...

The Conservation Atlas of Tropical Forests Africa, 1992

Based on thorough bibliographic research of a highly controversial topic, this report, jointly sp... more Based on thorough bibliographic research of a highly controversial topic, this report, jointly sponsored by IUCN, UNEP and WWF, shows the potential of plantations, while also exposing problems which may arise if massive tree plantations proposed for the tropics are to be established. Major issues covered include; species selection, soil and water cycle effects, fires, pests and diseases, effects on biodiversity, carbon dioxide fixation, land tenure and social issues, and plantation economics. Some broad conclusions and guidelines to be considered when establishing large scale plantations in the tropics complete this study.

BMJ, Jun 10, 2006

Scrums are contested in junior rugby Editor-Bourke's statement that contested scrums are not allo... more Scrums are contested in junior rugby Editor-Bourke's statement that contested scrums are not allowed in the under 19 game is incorrect. 1 Scrums in schoolboy games are certainly contested. The differences from the senior game in terms of contesting are that the scrum cannot be wheeled more than 45°as opposed to 90°, and the scrum is not allowed to be pushed more than 1.5 m. 2 He is also incorrect in stating that in rugby league pushing has not been allowed since 1996. It is technically still allowed according to the rule book, but it is accepted in the game that it is not done. 3 As someone who played rugby union from a very early age and is still playing now, I disagree with the author. I have never played in a game with such an injury in over 20 years, and the scrum does not just allow a tactical advantage-games are won and lost there. I attended a rugby playing school in England, where an excellent coach taught safety at the scrum first, then competent technique. Competent refereeing is also important in keeping players safe. Most players of rugby union, a hugely popular social game in the United Kingdom, are not professional and therefore would not be covered under the Health and Safety at Work Act. Players suffering such injuries should indeed be compensated adequately, and national union insurance policies should reflect this. Despite this, as members of their respective unions, rugby players are in a better position for such compensation than those independently undertaking such activities as horse riding and skiing or snowboarding, where the risk may be higher and any injuries sustained would be accountable only to themselves. The unfortunate events that Bourke has witnessed do not give sufficient case to change a game hundreds of thousands of people enjoy the way it is, despite knowing what could happen.

Lancet (London, England), Jan 5, 2015

for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of p... more for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of priority antivenoms from Dec 1, 2015. We are also ready to partner with all interested organisations to address this public health issue before existing technical capacity is lost and yet more lives are needlessly impaired or lost. We declare no competing interests.

The Lancet, Dec 1, 2015

for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of p... more for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of priority antivenoms from Dec 1, 2015. We are also ready to partner with all interested organisations to address this public health issue before existing technical capacity is lost and yet more lives are needlessly impaired or lost. We declare no competing interests.

Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation

The World Health Organisation develops and promotes international standards for pharmaceutical pr... more The World Health Organisation develops and promotes international standards for pharmaceutical products, in support of efforts to increase access to quality-assured medicines for all, and to safeguard patients from substandard and falsified medicines. The International Pharmacopoeia is a key output of this work. Its focus, processes to establish texts for inclusion or revision, response to COVID-19 and the collaboration with other Pharmacopoeias shall be discussed in this review. Pharmacopoeias provide public standards (written norms as well as physical reference standards), which ensure the quality of medicines by defining the attributes that are essential to their safety and efficacy. They consist of analytical methods to test for the identity, purity and content of pharmaceutical products, together with acceptance criteria to evaluate test results, and information about storage, labelling and production. Pharmacopoeias greatly facilitate the development of multi-source medicines ...

The Lancet, 2010

958 www.thelancet.com Vol 376 September 18, 2010 reason that our report stated the need for exten... more 958 www.thelancet.com Vol 376 September 18, 2010 reason that our report stated the need for extensive genotyping of APOA5 (and related loci) in relation to detailed lipoprotein assessments (such as those based on structural and functional characteristics). Jean Dallongeville and Aline Meirhaeghe suggest that caution should be exercised in interpreting our study because the results might not necessarily indicate a role for hypertriglyceridaemia itself, especially since triglyceride metabolism is modulated by factors such as diabetes, obesity, and smoking. It was due to such considerations that the title and conclusions of our report related to “triglyceride-mediated pathways” rather than to hypertriglyceridaemia. (Our study showed that the APOA5 –1131T>C genotype is not materially correlated to the prevalence of diabetes, obesity, and smoking.) Di Zeng and colleagues describe potential limitations of genetic association studies, including the possibility of confounding by other ge...

Journal of Cell Science, Jul 1, 1986

To evaluate the relative mobilities of cell surface glycoconjugates during myogenesis we have stu... more To evaluate the relative mobilities of cell surface glycoconjugates during myogenesis we have studied the redistribution of fluorescein-conjugated plant lectins on L6 rat myogenic cells. Previous experiments had demonstrated that the receptors for the lectins soybean agglutinin (SBA), wheat germ agglutinin, concanavalin A and Lens culinaris agglutinin all were relatively uniformly distributed on both myoblasts and myotubes, and that SBA receptors were capable of rapid redistribution on myotubes but not myoblasts at 4°C (Sawyer & Akeson, 1983). Here we show that when SBA-labelled myoblasts are incubated at 37°C, or for extended times at 4°C, the lectin aggregates as on myotubes. So it appears that SBA-binding components show a quantitative rather than qualitative change in their mobility during L6 differentiation. In addition, the redistribution of the three other lectins on myoblasts and myotubes was either 4ess prominent (i.e. showing fewer apparent surface clusters) or occurred less rapidly than with SBA. None of these three lectins showed striking differences in mobility between myoblasts and myotubes. Thus, it appears that SBA binds to a subset of surface glycoconjugates that is relatively highly mobile, and that this mobility is specifically enhanced with differentiation.

Health Professions - Clinical (The Ohio State University Denman Undergraduate Research Forum)

Proceedings of the National Academy of Sciences, 2011

Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major effo... more Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreov...

Proceedings of the National Academy of Sciences, 2010

Cervical carcinomas are initiated through a series of well-defined stages that rely on the expres... more Cervical carcinomas are initiated through a series of well-defined stages that rely on the expression of human papillomavirus (HPV) oncogenes. A panel of 100 small hairpin RNAs that target essential kinases in many tumor types was used to study the stepwise appearance of kinase requirements during cervical tumor development. Twenty-six kinases were commonly required in three cell lines derived from frank carcinomas, and each kinase requirement was traced to the specific stage in which the requirement emerged. Six kinases became required following HPV-induced immortalization, and the requirement for two kinases, SGK2 and PAK3, was mapped to the inactivation of p53 in primary human epithelial cells. Loss of the p53 tumor suppressor in other primary epithelial cells also induced dependence on SGK2 and PAK3. Hence, SGK2 and PAK3 provide important cellular functions following p53 inactivation, fulfilling the classical definition of synthetic lethality; loss of p53, SGK2, or PAK3 alone ha...

Proceedings of the National Academy of Sciences, 2008

shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promotin... more shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: ( i ) in repeat experiments using the same cells, ( ii ) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and ( iii ) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this stu...

Proceedings of the National Academy of Sciences, 2008

Functional differences among human cells have been difficult to identify by standard biochemical ... more Functional differences among human cells have been difficult to identify by standard biochemical methods. Loss-of-function shRNA screens provide an unbiased method to compare protein requirements across cell lines. In previous work, we have studied kinase requirements in two settings, either among a panel of cells from numerous tissues or between two cell lines that differ only by the expression of a chosen oncoprotein or tumor suppressor protein. Here we examine the patterns of kinase requirements between two unrelated cells, the cervical carcinoma cell line HeLa and the renal carcinoma cell line 786-O. By using time courses of cell proliferation after shRNA transduction and by introducing different levels of the shRNAs, we were able to carefully compare the kinase requirements. These comparisons identified 10 kinases that were required in HeLa but not 786-O, and 5 kinases that were required in 786-O but not HeLa. The patterns of growth inhibition due to particular sets of shRNAs i...

The Conservation Atlas of Tropical Forests Africa, 1992

Based on thorough bibliographic research of a highly controversial topic, this report, jointly sp... more Based on thorough bibliographic research of a highly controversial topic, this report, jointly sponsored by IUCN, UNEP and WWF, shows the potential of plantations, while also exposing problems which may arise if massive tree plantations proposed for the tropics are to be established. Major issues covered include; species selection, soil and water cycle effects, fires, pests and diseases, effects on biodiversity, carbon dioxide fixation, land tenure and social issues, and plantation economics. Some broad conclusions and guidelines to be considered when establishing large scale plantations in the tropics complete this study.

BMJ, Jun 10, 2006

Scrums are contested in junior rugby Editor-Bourke's statement that contested scrums are not allo... more Scrums are contested in junior rugby Editor-Bourke's statement that contested scrums are not allowed in the under 19 game is incorrect. 1 Scrums in schoolboy games are certainly contested. The differences from the senior game in terms of contesting are that the scrum cannot be wheeled more than 45°as opposed to 90°, and the scrum is not allowed to be pushed more than 1.5 m. 2 He is also incorrect in stating that in rugby league pushing has not been allowed since 1996. It is technically still allowed according to the rule book, but it is accepted in the game that it is not done. 3 As someone who played rugby union from a very early age and is still playing now, I disagree with the author. I have never played in a game with such an injury in over 20 years, and the scrum does not just allow a tactical advantage-games are won and lost there. I attended a rugby playing school in England, where an excellent coach taught safety at the scrum first, then competent technique. Competent refereeing is also important in keeping players safe. Most players of rugby union, a hugely popular social game in the United Kingdom, are not professional and therefore would not be covered under the Health and Safety at Work Act. Players suffering such injuries should indeed be compensated adequately, and national union insurance policies should reflect this. Despite this, as members of their respective unions, rugby players are in a better position for such compensation than those independently undertaking such activities as horse riding and skiing or snowboarding, where the risk may be higher and any injuries sustained would be accountable only to themselves. The unfortunate events that Bourke has witnessed do not give sufficient case to change a game hundreds of thousands of people enjoy the way it is, despite knowing what could happen.

Lancet (London, England), Jan 5, 2015

for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of p... more for the antivenoms area of work. Nevertheless, we are committed to starting prequalification of priority antivenoms from Dec 1, 2015. We are also ready to partner with all interested organisations to address this public health issue before existing technical capacity is lost and yet more lives are needlessly impaired or lost. We declare no competing interests.