aala jaberi | Boston University (original) (raw)
Papers by aala jaberi
Journal of the American Society of Nephrology, Oct 1, 2020
Journal of the American Society of Nephrology, Oct 1, 2020
Kidney Medicine, Dec 31, 2023
Seminars in Nephrology, 2022
Amyloid, Oct 9, 2019
BackgroundThe diagnostic utility of repeat kidney biopsy in AL amyloidosis patients in complete (... more BackgroundThe diagnostic utility of repeat kidney biopsy in AL amyloidosis patients in complete (CR) or very good partial hematologic response (VGPR) but with renal organ relapse is not clear.MethodsWe present 8 patients with AL amyloidosis who had a repeat kidney biopsy performed.ResultsAL amyloidosis was initially diagnosed by a kidney biopsy. All patients had a favorable response to treatment (CR/VGPR) and 5 of them also had initially a renal organ response. A repeat kidney biopsy was done due to gradual deterioration of kidney function and/or proteinuria while maintaining a hematologic response. Repeat kidney biopsies showed findings consistent with amyloid deposits in all patients. Seven patients had renal progression with 4 of them requiring dialysis initiation. Only one patient had a favorable renal outcome. This patient had subacute kidney injury with decreasing proteinuria and was found to have granulomatous interstitial nephritis in addition to amyloid deposits and responded well to steroid treatment with rapid improvement in renal function.ConclusionsIn AL amyloidosis patients who achieve a favorable hematologic response to treatment (CR/VGPR) but subsequently develop worsening renal insufficiency or proteinuria, a repeat kidney biopsy should generally not be performed. Amyloid deposits persist in the kidneys even after successful hematologic treatment and it is impossible to differentiate between new versus old amyloid deposits, which makes performing a repeat kidney biopsy unnecessary in most cases. Demonstration of amyloid deposits on repeat kidney biopsy would not aid in the decision making regarding re-initiation of hematologic treatment. A kidney biopsy should be considered only in cases when a specific alternative diagnosis is suspected.
Kidney medicine, Nov 1, 2020
A male college student presented to the emergency department with altered mental status and a ser... more A male college student presented to the emergency department with altered mental status and a serum ethanol level higher than the hospital laboratory assay. His course was complicated by mechanical ventilation, vasopressors, and cardiotoxicity. Thirteen hours into admission and despite aggressive supportive measures, the patient remained obtunded off sedation with serum ethanol level elevated at 428 mg/dL. A decision was made to initiate hemodialysis to expedite ethanol clearance and prevent further end-organ damage. Two hours into hemodialysis, mental status improved and serum ethanol level had decreased to 264 mg/dL. A total of 4 hours of hemodialysis were completed and serum ethanol level continued to downtrend. Dialysis increased the rate of ethanol elimination by a factor of 4 and prevented further cardiotoxicity or electrolyte level abnormalities. This case supports the use of hemodialysis for adult patients who meet the criteria of severe ethanol toxicity requiring critical care resources and having evidence of organ toxicity to 1 or more organ. Complete author and article information provided before references.
Kidney International Reports, Mar 1, 2018
Journal of Biological Chemistry, Feb 1, 2012
Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. R... more Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. Results: Mutations in serine and threonine residues in the activation segment of SLK reduced kinase activity. Conclusion: Phosphorylation of SLK plays a key role in activation and signaling. Significance: Understanding the regulation of SLK activity is essential for developing novel therapeutic approaches to renal injury. Expression and activation of the Ste20-like kinase, SLK, is increased during kidney development and recovery from ischemic acute kidney injury. SLK promotes apoptosis, and it may regulate cell survival during injury or repair. This study addresses the role of phosphorylation in the regulation of kinase activity. We mutated serine and threonine residues in the putative activation segment of the SLK catalytic domain and expressed wild type (WT) and mutant proteins in COS-1 or glomerular epithelial cells. Compared with SLK WT, the T183A, S189A, and T183A/S189A mutants showed reduced in vitro kinase activity. SLK WT, but not mutants, increased activationspecific phosphorylation of c-Jun N-terminal kinase (JNK) and p38 kinase. Similarly, SLK WT stimulated activator protein-1 reporter activity, but activation of activator protein-1 by the three SLK mutants was ineffective. To test if homodimerization of SLK affects phosphorylation, the cDNA encoding SLK amino acids 1-373 (which include the catalytic domain) was fused with a cDNA for a modified FK506-binding protein, Fv (Fv-SLK 1-373). After transfection, the addition of AP20187 (an FK506 analog) induced regulated dimerization of Fv-SLK 1-373. AP20187-stimulated dimerization enhanced the kinase activity of Fv-SLK 1-373 WT. In contrast, kinase activity of Fv-SLK 1-373 T183A/S189A was weak and was not enhanced after dimerization. Finally, apoptosis was increased after expression of Fv-SLK 1-373 WT but not T183A/S189A. Thus, phosphorylation of Thr-183 and Ser-189 plays a key role in the activation and signaling of SLK and could represent a target for novel therapeutic approaches to renal injury.
Cardiorenal medicine, Jun 19, 2024
Kidney International Reports, 2017
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2015
Wiener klinische Wochenschrift, 2012
Kidney Medicine, 2020
A male college student presented to the emergency department with altered mental status and a ser... more A male college student presented to the emergency department with altered mental status and a serum ethanol level higher than the hospital laboratory assay. His course was complicated by mechanical ventilation, vasopressors, and cardiotoxicity. Thirteen hours into admission and despite aggressive supportive measures, the patient remained obtunded off sedation with serum ethanol level elevated at 428 mg/dL. A decision was made to initiate hemodialysis to expedite ethanol clearance and prevent further end-organ damage. Two hours into hemodialysis, mental status improved and serum ethanol level had decreased to 264 mg/dL. A total of 4 hours of hemodialysis were completed and serum ethanol level continued to downtrend. Dialysis increased the rate of ethanol elimination by a factor of 4 and prevented further cardiotoxicity or electrolyte level abnormalities. This case supports the use of hemodialysis for adult patients who meet the criteria of severe ethanol toxicity requiring critical care resources and having evidence of organ toxicity to 1 or more organ. Complete author and article information provided before references.
Journal of Biological Chemistry, Dec 27, 2011
Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. R... more Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. Results: Mutations in serine and threonine residues in the activation segment of SLK reduced kinase activity. Conclusion: Phosphorylation of SLK plays a key role in activation and signaling. Significance: Understanding the regulation of SLK activity is essential for developing novel therapeutic approaches to renal injury. Expression and activation of the Ste20-like kinase, SLK, is increased during kidney development and recovery from ischemic acute kidney injury. SLK promotes apoptosis, and it may regulate cell survival during injury or repair. This study addresses the role of phosphorylation in the regulation of kinase activity. We mutated serine and threonine residues in the putative activation segment of the SLK catalytic domain and expressed wild type (WT) and mutant proteins in COS-1 or glomerular epithelial cells. Compared with SLK WT, the T183A, S189A, and T183A/S189A mutants showed reduced in vitro kinase activity. SLK WT, but not mutants, increased activationspecific phosphorylation of c-Jun N-terminal kinase (JNK) and p38 kinase. Similarly, SLK WT stimulated activator protein-1 reporter activity, but activation of activator protein-1 by the three SLK mutants was ineffective. To test if homodimerization of SLK affects phosphorylation, the cDNA encoding SLK amino acids 1-373 (which include the catalytic domain) was fused with a cDNA for a modified FK506-binding protein, Fv (Fv-SLK 1-373). After transfection, the addition of AP20187 (an FK506 analog) induced regulated dimerization of Fv-SLK 1-373. AP20187-stimulated dimerization enhanced the kinase activity of Fv-SLK 1-373 WT. In contrast, kinase activity of Fv-SLK 1-373 T183A/S189A was weak and was not enhanced after dimerization. Finally, apoptosis was increased after expression of Fv-SLK 1-373 WT but not T183A/S189A. Thus, phosphorylation of Thr-183 and Ser-189 plays a key role in the activation and signaling of SLK and could represent a target for novel therapeutic approaches to renal injury.
Journal of the American Society of Nephrology, Oct 1, 2020
Journal of the American Society of Nephrology, Oct 1, 2020
Kidney Medicine, Dec 31, 2023
Seminars in Nephrology, 2022
Amyloid, Oct 9, 2019
BackgroundThe diagnostic utility of repeat kidney biopsy in AL amyloidosis patients in complete (... more BackgroundThe diagnostic utility of repeat kidney biopsy in AL amyloidosis patients in complete (CR) or very good partial hematologic response (VGPR) but with renal organ relapse is not clear.MethodsWe present 8 patients with AL amyloidosis who had a repeat kidney biopsy performed.ResultsAL amyloidosis was initially diagnosed by a kidney biopsy. All patients had a favorable response to treatment (CR/VGPR) and 5 of them also had initially a renal organ response. A repeat kidney biopsy was done due to gradual deterioration of kidney function and/or proteinuria while maintaining a hematologic response. Repeat kidney biopsies showed findings consistent with amyloid deposits in all patients. Seven patients had renal progression with 4 of them requiring dialysis initiation. Only one patient had a favorable renal outcome. This patient had subacute kidney injury with decreasing proteinuria and was found to have granulomatous interstitial nephritis in addition to amyloid deposits and responded well to steroid treatment with rapid improvement in renal function.ConclusionsIn AL amyloidosis patients who achieve a favorable hematologic response to treatment (CR/VGPR) but subsequently develop worsening renal insufficiency or proteinuria, a repeat kidney biopsy should generally not be performed. Amyloid deposits persist in the kidneys even after successful hematologic treatment and it is impossible to differentiate between new versus old amyloid deposits, which makes performing a repeat kidney biopsy unnecessary in most cases. Demonstration of amyloid deposits on repeat kidney biopsy would not aid in the decision making regarding re-initiation of hematologic treatment. A kidney biopsy should be considered only in cases when a specific alternative diagnosis is suspected.
Kidney medicine, Nov 1, 2020
A male college student presented to the emergency department with altered mental status and a ser... more A male college student presented to the emergency department with altered mental status and a serum ethanol level higher than the hospital laboratory assay. His course was complicated by mechanical ventilation, vasopressors, and cardiotoxicity. Thirteen hours into admission and despite aggressive supportive measures, the patient remained obtunded off sedation with serum ethanol level elevated at 428 mg/dL. A decision was made to initiate hemodialysis to expedite ethanol clearance and prevent further end-organ damage. Two hours into hemodialysis, mental status improved and serum ethanol level had decreased to 264 mg/dL. A total of 4 hours of hemodialysis were completed and serum ethanol level continued to downtrend. Dialysis increased the rate of ethanol elimination by a factor of 4 and prevented further cardiotoxicity or electrolyte level abnormalities. This case supports the use of hemodialysis for adult patients who meet the criteria of severe ethanol toxicity requiring critical care resources and having evidence of organ toxicity to 1 or more organ. Complete author and article information provided before references.
Kidney International Reports, Mar 1, 2018
Journal of Biological Chemistry, Feb 1, 2012
Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. R... more Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. Results: Mutations in serine and threonine residues in the activation segment of SLK reduced kinase activity. Conclusion: Phosphorylation of SLK plays a key role in activation and signaling. Significance: Understanding the regulation of SLK activity is essential for developing novel therapeutic approaches to renal injury. Expression and activation of the Ste20-like kinase, SLK, is increased during kidney development and recovery from ischemic acute kidney injury. SLK promotes apoptosis, and it may regulate cell survival during injury or repair. This study addresses the role of phosphorylation in the regulation of kinase activity. We mutated serine and threonine residues in the putative activation segment of the SLK catalytic domain and expressed wild type (WT) and mutant proteins in COS-1 or glomerular epithelial cells. Compared with SLK WT, the T183A, S189A, and T183A/S189A mutants showed reduced in vitro kinase activity. SLK WT, but not mutants, increased activationspecific phosphorylation of c-Jun N-terminal kinase (JNK) and p38 kinase. Similarly, SLK WT stimulated activator protein-1 reporter activity, but activation of activator protein-1 by the three SLK mutants was ineffective. To test if homodimerization of SLK affects phosphorylation, the cDNA encoding SLK amino acids 1-373 (which include the catalytic domain) was fused with a cDNA for a modified FK506-binding protein, Fv (Fv-SLK 1-373). After transfection, the addition of AP20187 (an FK506 analog) induced regulated dimerization of Fv-SLK 1-373. AP20187-stimulated dimerization enhanced the kinase activity of Fv-SLK 1-373 WT. In contrast, kinase activity of Fv-SLK 1-373 T183A/S189A was weak and was not enhanced after dimerization. Finally, apoptosis was increased after expression of Fv-SLK 1-373 WT but not T183A/S189A. Thus, phosphorylation of Thr-183 and Ser-189 plays a key role in the activation and signaling of SLK and could represent a target for novel therapeutic approaches to renal injury.
Cardiorenal medicine, Jun 19, 2024
Kidney International Reports, 2017
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2015
Wiener klinische Wochenschrift, 2012
Kidney Medicine, 2020
A male college student presented to the emergency department with altered mental status and a ser... more A male college student presented to the emergency department with altered mental status and a serum ethanol level higher than the hospital laboratory assay. His course was complicated by mechanical ventilation, vasopressors, and cardiotoxicity. Thirteen hours into admission and despite aggressive supportive measures, the patient remained obtunded off sedation with serum ethanol level elevated at 428 mg/dL. A decision was made to initiate hemodialysis to expedite ethanol clearance and prevent further end-organ damage. Two hours into hemodialysis, mental status improved and serum ethanol level had decreased to 264 mg/dL. A total of 4 hours of hemodialysis were completed and serum ethanol level continued to downtrend. Dialysis increased the rate of ethanol elimination by a factor of 4 and prevented further cardiotoxicity or electrolyte level abnormalities. This case supports the use of hemodialysis for adult patients who meet the criteria of severe ethanol toxicity requiring critical care resources and having evidence of organ toxicity to 1 or more organ. Complete author and article information provided before references.
Journal of Biological Chemistry, Dec 27, 2011
Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. R... more Background: SLK promotes apoptosis and may control cell survival during renal injury or repair. Results: Mutations in serine and threonine residues in the activation segment of SLK reduced kinase activity. Conclusion: Phosphorylation of SLK plays a key role in activation and signaling. Significance: Understanding the regulation of SLK activity is essential for developing novel therapeutic approaches to renal injury. Expression and activation of the Ste20-like kinase, SLK, is increased during kidney development and recovery from ischemic acute kidney injury. SLK promotes apoptosis, and it may regulate cell survival during injury or repair. This study addresses the role of phosphorylation in the regulation of kinase activity. We mutated serine and threonine residues in the putative activation segment of the SLK catalytic domain and expressed wild type (WT) and mutant proteins in COS-1 or glomerular epithelial cells. Compared with SLK WT, the T183A, S189A, and T183A/S189A mutants showed reduced in vitro kinase activity. SLK WT, but not mutants, increased activationspecific phosphorylation of c-Jun N-terminal kinase (JNK) and p38 kinase. Similarly, SLK WT stimulated activator protein-1 reporter activity, but activation of activator protein-1 by the three SLK mutants was ineffective. To test if homodimerization of SLK affects phosphorylation, the cDNA encoding SLK amino acids 1-373 (which include the catalytic domain) was fused with a cDNA for a modified FK506-binding protein, Fv (Fv-SLK 1-373). After transfection, the addition of AP20187 (an FK506 analog) induced regulated dimerization of Fv-SLK 1-373. AP20187-stimulated dimerization enhanced the kinase activity of Fv-SLK 1-373 WT. In contrast, kinase activity of Fv-SLK 1-373 T183A/S189A was weak and was not enhanced after dimerization. Finally, apoptosis was increased after expression of Fv-SLK 1-373 WT but not T183A/S189A. Thus, phosphorylation of Thr-183 and Ser-189 plays a key role in the activation and signaling of SLK and could represent a target for novel therapeutic approaches to renal injury.