Molecular breeding : new strategies in plant improvement, 2018
Adult plant resistance against plant pathogens is of interest as a means to achieve durable resis... more Adult plant resistance against plant pathogens is of interest as a means to achieve durable resistance. Prior to this research, the barley lines CLE210 (from Uruguay) and Denar (from the Czech Republic) had been reported to exhibit adult-plant resistance against powdery mildew. Here, populations of doubled haploid lines from crosses of these lines with the susceptible cultivar Baudin were evaluated for powdery mildew resistance in field experiments. Using linkage maps constructed from genotyping-by-sequencing (GBS) data, it was determined that differences in resistance were largely attributable to a region on the long arm of chromosome 5H (5HL). Therefore, KASP assays were developed based on GBS tag sequences mapped on that chromosome, providing more reliable genetic maps. In each population, a large-effect QTL was mapped on 5HL. As no sequence variation was detected between CLE210 and Denar in this region of 5HL, the two sources of resistance may be identical by descent in the QTL ...
The aim of this manuscript is to review available data to evaluate the present status of proprote... more The aim of this manuscript is to review available data to evaluate the present status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed. The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol and other atherogenic lipid fractions was studied in various Phase 2 and Phase 3 trials of Alirocumab, Evolocumab, and Bococizumab. The results of published long-term ODYSSEY and OSLER studies are summarized. There have been three excellent meta-analysis studies on PCSK9 inhibitors which are outlined. The complex problem of cost-effectiveness was carefully evaluated by the Institute for Clinical and Economic Review (ICER). The draft report (ICER-2015) is summarized herewith. The cardiovascular outcome trials with Evolocumab (FOURIER), Alirocumab (ODYSSEY OUTCOME) and Bococizumab (SPIRE-1 and SPIRE-2) are the ongoing clinical trials, and their results are expected...
Journal of Hepato-Biliary-Pancreatic Sciences, 2016
Telomeres play an important role in cancer progression. Recently it has been shown that subtelome... more Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones. Relative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non-tumor. We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones. This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels.
Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention... more Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20-30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through 'Risk evaluation and Mitigation Strategy (REMS)'. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and ...
Tetralogy of Fallot is one of the commonest congenital cyanotic heart disease affecting children ... more Tetralogy of Fallot is one of the commonest congenital cyanotic heart disease affecting children older than one year of age. Apart from its classical features it is associated with certain extra-cardiac manifestations which occur in varying frequency. They include CATCH22 monosomy, Down’s Syndrome, Velocardiofacial abnormalities, CHARGE Syndrome, Goldenhar Syndrome (Occulo-auriculo-vertebral),Poland Syndrome, Syndactyly, Brachydactyly and Hypoplasia of Ipsilatral hand.
Catheterization and Cardiovascular Diagnosis, 1998
Pharmacological therapy remains the treatment of choice for Prinzmetal angina. We report an uncon... more Pharmacological therapy remains the treatment of choice for Prinzmetal angina. We report an unconventional approach of coronary artery stenting to treat coronary artery spasm in variant angina refractory to triple drug therapy. Favorable clinical and angiographic results and a negative Ergonovine test, under less aggressive medical therapy, are valuable arguments for stenting. Four-month angiographic follow-up showed absence of intrastent restenosis with a negative Ergonovine test. However, long-term follow-up is necessary before advocating this as a systematic approach.
Molecular breeding : new strategies in plant improvement, 2018
Adult plant resistance against plant pathogens is of interest as a means to achieve durable resis... more Adult plant resistance against plant pathogens is of interest as a means to achieve durable resistance. Prior to this research, the barley lines CLE210 (from Uruguay) and Denar (from the Czech Republic) had been reported to exhibit adult-plant resistance against powdery mildew. Here, populations of doubled haploid lines from crosses of these lines with the susceptible cultivar Baudin were evaluated for powdery mildew resistance in field experiments. Using linkage maps constructed from genotyping-by-sequencing (GBS) data, it was determined that differences in resistance were largely attributable to a region on the long arm of chromosome 5H (5HL). Therefore, KASP assays were developed based on GBS tag sequences mapped on that chromosome, providing more reliable genetic maps. In each population, a large-effect QTL was mapped on 5HL. As no sequence variation was detected between CLE210 and Denar in this region of 5HL, the two sources of resistance may be identical by descent in the QTL ...
The aim of this manuscript is to review available data to evaluate the present status of proprote... more The aim of this manuscript is to review available data to evaluate the present status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed. The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol and other atherogenic lipid fractions was studied in various Phase 2 and Phase 3 trials of Alirocumab, Evolocumab, and Bococizumab. The results of published long-term ODYSSEY and OSLER studies are summarized. There have been three excellent meta-analysis studies on PCSK9 inhibitors which are outlined. The complex problem of cost-effectiveness was carefully evaluated by the Institute for Clinical and Economic Review (ICER). The draft report (ICER-2015) is summarized herewith. The cardiovascular outcome trials with Evolocumab (FOURIER), Alirocumab (ODYSSEY OUTCOME) and Bococizumab (SPIRE-1 and SPIRE-2) are the ongoing clinical trials, and their results are expected...
Journal of Hepato-Biliary-Pancreatic Sciences, 2016
Telomeres play an important role in cancer progression. Recently it has been shown that subtelome... more Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones. Relative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non-tumor. We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones. This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels.
Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention... more Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20-30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through 'Risk evaluation and Mitigation Strategy (REMS)'. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and ...
Tetralogy of Fallot is one of the commonest congenital cyanotic heart disease affecting children ... more Tetralogy of Fallot is one of the commonest congenital cyanotic heart disease affecting children older than one year of age. Apart from its classical features it is associated with certain extra-cardiac manifestations which occur in varying frequency. They include CATCH22 monosomy, Down’s Syndrome, Velocardiofacial abnormalities, CHARGE Syndrome, Goldenhar Syndrome (Occulo-auriculo-vertebral),Poland Syndrome, Syndactyly, Brachydactyly and Hypoplasia of Ipsilatral hand.
Catheterization and Cardiovascular Diagnosis, 1998
Pharmacological therapy remains the treatment of choice for Prinzmetal angina. We report an uncon... more Pharmacological therapy remains the treatment of choice for Prinzmetal angina. We report an unconventional approach of coronary artery stenting to treat coronary artery spasm in variant angina refractory to triple drug therapy. Favorable clinical and angiographic results and a negative Ergonovine test, under less aggressive medical therapy, are valuable arguments for stenting. Four-month angiographic follow-up showed absence of intrastent restenosis with a negative Ergonovine test. However, long-term follow-up is necessary before advocating this as a systematic approach.
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