Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1977
SummaryThe ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal l... more SummaryThe ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal level was 269 ±95 units/ml. Consistent elevations above 550 units/ml were found in. 1 Chronic cerebrovascular disease, 2 Spinal cord compression; 3. Tumors. The molecular weights of the ribonucleases in the cerebrospinal fluid are approximately 33,000; 21,000 and 15,000, the major species is the one with m w. 33,000.Although the increase in the CSF ribonuclease activity is not disease specific, the measurement has provided corroborative help in cases when the CSF protein is normal.The increase in CSF RNAase is not due to red or white blood cells and the immunologie data suggest that the CSF enzyme activity is derived from the blood stream Further studies are necessary to rule out a nerve cell origin of the CSF ribonuclease activity.
Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal flu... more Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal fluid and urine of humans. Purified human urinary ribonuclease was used to produce a monospecific antibody in rabbits. The antibody was capable of: (i) inhibiting the enzyme activities in the serum, CSF, and urine; (ii) reacting with antigens in the serum and CSF. The antigens in the serum, CSF and urine were found to be immunologically identical. Immunoelectrophoresis data suggested that the urinary and CSF RNAase are chemically identical. Succesful renal transplantation reduced elevated serum RNAase to normal levels. The data suggest that the most likely source of both urinary and CSF ribonuclease activity is the blood stream.
Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1972
An exonuclease specific for single-stranded nucleic acids has been purified from Neurospora crass... more An exonuclease specific for single-stranded nucleic acids has been purified from Neurospora crassa conidia. The enzyme had a molecular weight of 72 ooo and consisted of a single polypeptide chain. It degraded single-stranded DNA and RNA to 5'mononucleotides and oligonucleotides. In a IO % digest of single-stranded DNA, 72 % of the ultraviolet-absorbing material was found in mononucleotides (I-mers) and 28 % in 2-9-mers. No detectable acid-soluble material was released from either double-stranded DNA or native reovirus RNA. There was some base specificity in the nuclease attack since the compositions of the mononucleotide fractions of early digests of single-stranded DNA and ribosomal RNA were respectively 68 % dTMP, 13 % dAMP, 12 % dGMP, 7 % dCMP and 62 % UMP, 20 % GMP, 9 % AMP, 9 % CMP. The direction of exonucleolytic attack on 5'-3*P-labelled pyrimidine heptadeoxyribonucleotides was 5'-~ 3'-The exonuclease destroyed the infectivity of single-stranded circular q~xI74 DNA rapidly, but onlyveryslowly converted superhelical SI3 replicative form I DNA to the replicative form II form. The enzyme preparation, therefore, also contained some endonuclease activity specific for single-stranded DNA. In the presence of lO-3 IV[ Mg2., the action of the enzyme on poly(rA) was predominantly exonucleolytic, but in the absence of Mg~+ it was endonucleolytic in character, Tile exonuclease was optimally active with denatured DNA at pH 8.5 in the presence of o.oi IV[ ~g2+ and with ribosomal RNA at pH 8.3 in the presence of lO .3 ~ Yig~+. The activity was unaffected by 4-8 m~ mercaptoethanol and by I m~ p-hydroxymercuribenzoate, but increases in ionic strength above o.i inhibited the activity. Under optimal conditions, the activity with either DNA or ribosomal RNA was not affected by o.2-o.4 mlV[ ATP, an inhibitor of N. crassa endonuclease. The exonuclease was unstable at pH 8.5 in tile presence of o.oi IV[ Mg '+ with a half-life of 27 min at 37 °. It was more stable in the presence of single-stranded DNA, io 4 M dTNP or IO-~ M AMP.
AT is an autosomal-recessive syndrome characterized by neurologic abnormalities, variable ID, and... more AT is an autosomal-recessive syndrome characterized by neurologic abnormalities, variable ID, and a 10% prevalence rate of cancer at a mean age of 12.5 yrs. AT patients have excess proportions of lymphoid tumors and selected carcinomas compared to types in the general population. AT lymphomas resemble nonlymph
A radiochemical method for the determination of the amino terminus on very small amounts (0.5–5 n... more A radiochemical method for the determination of the amino terminus on very small amounts (0.5–5 nmol) of protein is described. The high sensitivity of the method is achieved by using undiluted 1-fluoro-2,4-dinitro-[3,5-3H]benzene ([3H]Dnp-F) as the labelling reagent under conditions in which a maximum amount of radioactive label is incorporated. Chemical homogeneity is achieved by reacting with excess unlabelled Dnp-F. High recovery is obtained by adding Dnp-albumin as carrier protein. A mixture of Dnp 14C-labelled amino acids is added prior to hydrolysis and identification of the amino terminus is made on the basis of the 3H/14C ratios of the separated Dnp-amino acids. The method was tested on insulin, pancreatic ribonuclease, and lysozyme which gave high 3H/14C ratios only in the expected amino-terminal amino acids. Application to multiple forms of poly(C)-avid ribonuclease gave only amino-terminal lysine. Two of four putative isozymes of 17β-hydroxysteroid dehydrogenase had serin...
Supplemental material, Appendices for Major Outcomes With Personalized Dialysate TEMPerature (MyT... more Supplemental material, Appendices for Major Outcomes With Personalized Dialysate TEMPerature (MyTEMP): Rationale and Design of a Pragmatic, Registry-Based, Cluster Randomized Controlled Trial by Ahmed A. Al-Jaishi, Christopher W. McIntyre, Jessica M. Sontrop, Stephanie N. Dixon, Sierra Anderson, Amit Bagga, Derek Benjamin, David Berry, Peter G. Blake, Laura Chambers, Patricia C. K. Chan, Nicole Delbrouck, P. J. Devereaux, Luis F. Ferreira-Divino, Richard Goluch, Laura Gregor, Jeremy M. Grimshaw, Garth Hanson, Eduard Iliescu, Arsh K. Jain, Charmaine E. Lok, Reem A. Mustafa, Bharat Nathoo, Gihad E. Nesrallah, Matthew J. Oliver, Sanjay Pandeya, Malvinder S. Parmar, David Perkins, Justin Presseau, Eli Rabin, Joanna Sasal, Tanya Shulman, Manish M. Sood, Andrew Steele, Paul Tam, Daniel Tascona, Davinder Wadehra, Ron Wald, Michael Walsh, Paul Watson, Walter Wodchis, Phillip Zager, Merrick Zwarenstein and Amit X. Garg in Canadian Journal of Kidney Health and Disease
Background:Small randomized trials demonstrated that a lower compared with higher dialysate tempe... more Background:Small randomized trials demonstrated that a lower compared with higher dialysate temperature reduced the average drop in intradialytic blood pressure. Some observational studies demonstrated that a lower compared with higher dialysate temperature was associated with a lower risk of all-cause mortality and cardiovascular mortality. There is now the need for a large randomized trial that compares the effect of a low vs high dialysate temperature on major cardiovascular outcomes.Objective:The purpose of this study is to test the effect of outpatient hemodialysis centers randomized to (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol for 4 years on cardiovascular-related death and hospitalizations.Design:The design of the study is a pragmatic, registry-based, open-label, cluster randomized controlled trial.Setting:Hemodialysis centers in Ontario, Canada, were randomized on February 1, 2017, for a trial start date of Apr...
The anemia of chronic renal failure was studied by assessing the effect of uremic serum on prolif... more The anemia of chronic renal failure was studied by assessing the effect of uremic serum on proliferation of human marrow erythroid stem cells into colonies in vitro. Of 50 sera tested, 46 inhibited "CFU-E" colony formation by a mean of 72%, and 42 inhibited "BFU-E" colonies by a mean of 53.5%, compared to normal sera. Analysis of the uremic sera revealed a striking increase of ribonuclease activity in every patient. Mean activity in the study group was 17,346 U/ml serum (range 6,700-36,250) compared to control mean of 1,047 +/- 247 U/ml. Purified ribonuclease added to marrow cultures in concentrations simulating uremic serum produced a dose-dependent decrease in CFU-E colonies suggesting that the substance has a role in the production of anemia of renal failure.
Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life ... more Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Critical Care Med... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Critical Care Medicine. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to ...
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1982
A low molecular weight ribonuelease (M, 18000) was isolated and purified from human uremic serum,... more A low molecular weight ribonuelease (M, 18000) was isolated and purified from human uremic serum, as determined by Sephadex gel filtration and SDS-polyacrylamide gel electrophoresis. Its relationship to the human urinary ribonuclease (/14, 33 000) is investigated in the following paper.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1977
SummaryThe ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal l... more SummaryThe ribonuclease activity of cerebrospinal fluid of 219 patients was studied. The normal level was 269 ±95 units/ml. Consistent elevations above 550 units/ml were found in. 1 Chronic cerebrovascular disease, 2 Spinal cord compression; 3. Tumors. The molecular weights of the ribonucleases in the cerebrospinal fluid are approximately 33,000; 21,000 and 15,000, the major species is the one with m w. 33,000.Although the increase in the CSF ribonuclease activity is not disease specific, the measurement has provided corroborative help in cases when the CSF protein is normal.The increase in CSF RNAase is not due to red or white blood cells and the immunologie data suggest that the CSF enzyme activity is derived from the blood stream Further studies are necessary to rule out a nerve cell origin of the CSF ribonuclease activity.
Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal flu... more Poly(C)-avid ribonucleases of molecular weight 33 000 are present in the serum, cerebrospinal fluid and urine of humans. Purified human urinary ribonuclease was used to produce a monospecific antibody in rabbits. The antibody was capable of: (i) inhibiting the enzyme activities in the serum, CSF, and urine; (ii) reacting with antigens in the serum and CSF. The antigens in the serum, CSF and urine were found to be immunologically identical. Immunoelectrophoresis data suggested that the urinary and CSF RNAase are chemically identical. Succesful renal transplantation reduced elevated serum RNAase to normal levels. The data suggest that the most likely source of both urinary and CSF ribonuclease activity is the blood stream.
Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1972
An exonuclease specific for single-stranded nucleic acids has been purified from Neurospora crass... more An exonuclease specific for single-stranded nucleic acids has been purified from Neurospora crassa conidia. The enzyme had a molecular weight of 72 ooo and consisted of a single polypeptide chain. It degraded single-stranded DNA and RNA to 5'mononucleotides and oligonucleotides. In a IO % digest of single-stranded DNA, 72 % of the ultraviolet-absorbing material was found in mononucleotides (I-mers) and 28 % in 2-9-mers. No detectable acid-soluble material was released from either double-stranded DNA or native reovirus RNA. There was some base specificity in the nuclease attack since the compositions of the mononucleotide fractions of early digests of single-stranded DNA and ribosomal RNA were respectively 68 % dTMP, 13 % dAMP, 12 % dGMP, 7 % dCMP and 62 % UMP, 20 % GMP, 9 % AMP, 9 % CMP. The direction of exonucleolytic attack on 5'-3*P-labelled pyrimidine heptadeoxyribonucleotides was 5'-~ 3'-The exonuclease destroyed the infectivity of single-stranded circular q~xI74 DNA rapidly, but onlyveryslowly converted superhelical SI3 replicative form I DNA to the replicative form II form. The enzyme preparation, therefore, also contained some endonuclease activity specific for single-stranded DNA. In the presence of lO-3 IV[ Mg2., the action of the enzyme on poly(rA) was predominantly exonucleolytic, but in the absence of Mg~+ it was endonucleolytic in character, Tile exonuclease was optimally active with denatured DNA at pH 8.5 in the presence of o.oi IV[ ~g2+ and with ribosomal RNA at pH 8.3 in the presence of lO .3 ~ Yig~+. The activity was unaffected by 4-8 m~ mercaptoethanol and by I m~ p-hydroxymercuribenzoate, but increases in ionic strength above o.i inhibited the activity. Under optimal conditions, the activity with either DNA or ribosomal RNA was not affected by o.2-o.4 mlV[ ATP, an inhibitor of N. crassa endonuclease. The exonuclease was unstable at pH 8.5 in tile presence of o.oi IV[ Mg '+ with a half-life of 27 min at 37 °. It was more stable in the presence of single-stranded DNA, io 4 M dTNP or IO-~ M AMP.
AT is an autosomal-recessive syndrome characterized by neurologic abnormalities, variable ID, and... more AT is an autosomal-recessive syndrome characterized by neurologic abnormalities, variable ID, and a 10% prevalence rate of cancer at a mean age of 12.5 yrs. AT patients have excess proportions of lymphoid tumors and selected carcinomas compared to types in the general population. AT lymphomas resemble nonlymph
A radiochemical method for the determination of the amino terminus on very small amounts (0.5–5 n... more A radiochemical method for the determination of the amino terminus on very small amounts (0.5–5 nmol) of protein is described. The high sensitivity of the method is achieved by using undiluted 1-fluoro-2,4-dinitro-[3,5-3H]benzene ([3H]Dnp-F) as the labelling reagent under conditions in which a maximum amount of radioactive label is incorporated. Chemical homogeneity is achieved by reacting with excess unlabelled Dnp-F. High recovery is obtained by adding Dnp-albumin as carrier protein. A mixture of Dnp 14C-labelled amino acids is added prior to hydrolysis and identification of the amino terminus is made on the basis of the 3H/14C ratios of the separated Dnp-amino acids. The method was tested on insulin, pancreatic ribonuclease, and lysozyme which gave high 3H/14C ratios only in the expected amino-terminal amino acids. Application to multiple forms of poly(C)-avid ribonuclease gave only amino-terminal lysine. Two of four putative isozymes of 17β-hydroxysteroid dehydrogenase had serin...
Supplemental material, Appendices for Major Outcomes With Personalized Dialysate TEMPerature (MyT... more Supplemental material, Appendices for Major Outcomes With Personalized Dialysate TEMPerature (MyTEMP): Rationale and Design of a Pragmatic, Registry-Based, Cluster Randomized Controlled Trial by Ahmed A. Al-Jaishi, Christopher W. McIntyre, Jessica M. Sontrop, Stephanie N. Dixon, Sierra Anderson, Amit Bagga, Derek Benjamin, David Berry, Peter G. Blake, Laura Chambers, Patricia C. K. Chan, Nicole Delbrouck, P. J. Devereaux, Luis F. Ferreira-Divino, Richard Goluch, Laura Gregor, Jeremy M. Grimshaw, Garth Hanson, Eduard Iliescu, Arsh K. Jain, Charmaine E. Lok, Reem A. Mustafa, Bharat Nathoo, Gihad E. Nesrallah, Matthew J. Oliver, Sanjay Pandeya, Malvinder S. Parmar, David Perkins, Justin Presseau, Eli Rabin, Joanna Sasal, Tanya Shulman, Manish M. Sood, Andrew Steele, Paul Tam, Daniel Tascona, Davinder Wadehra, Ron Wald, Michael Walsh, Paul Watson, Walter Wodchis, Phillip Zager, Merrick Zwarenstein and Amit X. Garg in Canadian Journal of Kidney Health and Disease
Background:Small randomized trials demonstrated that a lower compared with higher dialysate tempe... more Background:Small randomized trials demonstrated that a lower compared with higher dialysate temperature reduced the average drop in intradialytic blood pressure. Some observational studies demonstrated that a lower compared with higher dialysate temperature was associated with a lower risk of all-cause mortality and cardiovascular mortality. There is now the need for a large randomized trial that compares the effect of a low vs high dialysate temperature on major cardiovascular outcomes.Objective:The purpose of this study is to test the effect of outpatient hemodialysis centers randomized to (1) a personalized temperature-reduced dialysate protocol or (2) a standard-temperature dialysate protocol for 4 years on cardiovascular-related death and hospitalizations.Design:The design of the study is a pragmatic, registry-based, open-label, cluster randomized controlled trial.Setting:Hemodialysis centers in Ontario, Canada, were randomized on February 1, 2017, for a trial start date of Apr...
The anemia of chronic renal failure was studied by assessing the effect of uremic serum on prolif... more The anemia of chronic renal failure was studied by assessing the effect of uremic serum on proliferation of human marrow erythroid stem cells into colonies in vitro. Of 50 sera tested, 46 inhibited "CFU-E" colony formation by a mean of 72%, and 42 inhibited "BFU-E" colonies by a mean of 53.5%, compared to normal sera. Analysis of the uremic sera revealed a striking increase of ribonuclease activity in every patient. Mean activity in the study group was 17,346 U/ml serum (range 6,700-36,250) compared to control mean of 1,047 +/- 247 U/ml. Purified ribonuclease added to marrow cultures in concentrations simulating uremic serum produced a dose-dependent decrease in CFU-E colonies suggesting that the substance has a role in the production of anemia of renal failure.
Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life ... more Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Critical Care Med... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Critical Care Medicine. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to ...
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1982
A low molecular weight ribonuelease (M, 18000) was isolated and purified from human uremic serum,... more A low molecular weight ribonuelease (M, 18000) was isolated and purified from human uremic serum, as determined by Sephadex gel filtration and SDS-polyacrylamide gel electrophoresis. Its relationship to the human urinary ribonuclease (/14, 33 000) is investigated in the following paper.
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