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Christopher P. Larsen - One of the best experts on this subject based on the ideXlab platform.

  • leukocyte Chemotactic Factor 2 amyloidosis alect2 is a common form of renal amyloidosis among egyptians
    Modern Pathology, 2016
    Co-Authors: Christopher P. Larsen, Wesam Ismail, Paul J Kurtin, Julie A Vrana, Surendra Dasari, Samih H Nasr
    Abstract:

    Large case series of renal amyloidosis subtypes have recently been published in the United States and Europe showing AL amyloidosis to be the predominant subtype in this part of the world. However, the most common subtypes of renal amyloidosis throughout the rest of the world are unknown. We present here the first large case series detailing the subtypes of renal amyloidosis among Egyptians. In this population, AA amyloidosis was the most common type of amyloidosis on renal biopsy at 48%. The newly described leukocyte Chemotactic Factor 2 amyloidosis (ALECT2) was the second most common type and represented nearly one-third of renal amyloid cases at 31%. AL accounted for only 20% of cases. The pathologic findings in ALECT2 cases were similar to those previously described in other case series. Thus ALECT2, which was initially thought to affect mainly Hispanics in the United States, appears to represent an important and likely underrecognized etiology of chronic kidney disease among Egyptians and probably in other ethnic groups around the world.

  • prevalence and organ distribution of leukocyte Chemotactic Factor 2 amyloidosis alect2 among decedents in new mexico
    Amyloid, 2016
    Co-Authors: Christopher P. Larsen, Marjorie L Beggs, Jon D Wilson, Sarah L Lathrop
    Abstract:

    Leukocyte Chemotactic Factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population.

  • clinical morphologic and genetic features of renal leukocyte Chemotactic Factor 2 amyloidosis
    Kidney International, 2014
    Co-Authors: Christopher P. Larsen, Alan Solomon, Robert J Kossmann, Marjorie L Beggs, Patrick D Walker
    Abstract:

    Leukocyte Chemotactic Factor 2 amyloidosis (ALECT2) is a recently described form of amyloidosis that most frequently manifests clinically with progressive renal failure. In a series of 414 cases of amyloidosis, there were 40 cases of ALECT2: the second most common type of renal amyloidosis in this series. This was particularly common in Hispanic patients in the Southwest United States, where more than half of amyloidosis cases were ALECT2. It is possible that this represents a familial amyloidosis as there were two brothers with ALECT2 in our study. Morphologically, there was consistent amyloid deposition in the renal cortex with medullary involvement in only about a third of cases. There were no mutations detected in the LECT2 gene, although all patients tested were homozygous for the G nucleotide in a non-synonymous SNP at position 172. Most patients presented with chronic kidney disease and, on follow-up, showed progression with an average deterioration in renal function of 0.5ml/min/1.73m 2 per month. Unfortunately, the etiology of ALECT2 is currently unknown and there is currently no efficacious treatment of the disease.

  • Leukocyte Chemotactic Factor 2 (LECT2)-associated renal amyloidosis.
    Amyloid, 2011
    Co-Authors: Charles L. Murphy, S Wang, Daniel P. Kestler, Christopher P. Larsen, Don M. Benson, Deborah T. Weiss, Alan Solomon
    Abstract:

    Abstract: In substantiation of a recent account of a patient whose renal amyloid deposits were formed from leukocyte Chemotactic Factor 2 (LECT2), we report 10 additional cases in adults ranging in...

  • leukocyte Chemotactic Factor 2 lect2 associated renal amyloidosis a case series
    American Journal of Kidney Diseases, 2010
    Co-Authors: Charles L. Murphy, S Wang, Daniel P. Kestler, Christopher P. Larsen, Don M. Benson, Deborah T. Weiss, Alan Solomon
    Abstract:

    Background Renal amyloidosis is characterized by the pathologic deposition within glomeruli and/or interstitium of congophilic fibrils, most often composed of either immunoglobulin light chains or serum amyloid A–related protein and, less commonly, mutated forms of apolipoproteins AI or AII, lysozyme, fibrinogen, gelsolin, or transthyretin. Study Design Case series. Setting & Participants 10 patients with renal amyloidosis who had an amyloidogenic protein that was not identified using routine immunohistochemistry. Outcomes Clinical, pathologic, biochemical, and genetic characteristics. Measurements Tandem mass spectrometry was used to analyze fibrils extracted from sections of formalin-fixed paraffin-embedded amyloid-containing kidney biopsy specimen blocks. Results Chemical analyses showed peptides corresponding to the carboxy-terminal portion of the leukocyte Chemotactic Factor 2 (LECT2) molecule. In addition, deposits were immunostained using an anti–human LECT2 monoclonal antibody. Plasma specimens were available from 2 individuals for whom LECT2 concentration in these samples was within the reference range. Additionally, in 4 of the cases analyzed at the molecular level, isolation of genomic DNA and polymerase chain reaction amplification of LECT2-encoding exons showed no mutations. However, all were homozygous for the G allele encoding valine at position 40 in the mature protein, a finding confirmed using restriction enzyme analysis of the polymorphic site. Limitations Causality is not addressed. Conclusions Based on our studies, we posit that LECT2-associated renal amyloidosis represents a unique and perhaps not uncommon disease, especially in Mexican Americans. The pathogenesis, extent, and prognosis remain to be determined.

Alan Solomon - One of the best experts on this subject based on the ideXlab platform.

  • clinical morphologic and genetic features of renal leukocyte Chemotactic Factor 2 amyloidosis
    Kidney International, 2014
    Co-Authors: Christopher P. Larsen, Alan Solomon, Robert J Kossmann, Marjorie L Beggs, Patrick D Walker
    Abstract:

    Leukocyte Chemotactic Factor 2 amyloidosis (ALECT2) is a recently described form of amyloidosis that most frequently manifests clinically with progressive renal failure. In a series of 414 cases of amyloidosis, there were 40 cases of ALECT2: the second most common type of renal amyloidosis in this series. This was particularly common in Hispanic patients in the Southwest United States, where more than half of amyloidosis cases were ALECT2. It is possible that this represents a familial amyloidosis as there were two brothers with ALECT2 in our study. Morphologically, there was consistent amyloid deposition in the renal cortex with medullary involvement in only about a third of cases. There were no mutations detected in the LECT2 gene, although all patients tested were homozygous for the G nucleotide in a non-synonymous SNP at position 172. Most patients presented with chronic kidney disease and, on follow-up, showed progression with an average deterioration in renal function of 0.5ml/min/1.73m 2 per month. Unfortunately, the etiology of ALECT2 is currently unknown and there is currently no efficacious treatment of the disease.

  • Leukocyte Chemotactic Factor 2 (LECT2)-associated renal amyloidosis.
    Amyloid, 2011
    Co-Authors: Charles L. Murphy, S Wang, Daniel P. Kestler, Christopher P. Larsen, Don M. Benson, Deborah T. Weiss, Alan Solomon
    Abstract:

    Abstract: In substantiation of a recent account of a patient whose renal amyloid deposits were formed from leukocyte Chemotactic Factor 2 (LECT2), we report 10 additional cases in adults ranging in...

  • leukocyte Chemotactic Factor 2 lect2 associated renal amyloidosis a case series
    American Journal of Kidney Diseases, 2010
    Co-Authors: Charles L. Murphy, S Wang, Daniel P. Kestler, Christopher P. Larsen, Don M. Benson, Deborah T. Weiss, Alan Solomon
    Abstract:

    Background Renal amyloidosis is characterized by the pathologic deposition within glomeruli and/or interstitium of congophilic fibrils, most often composed of either immunoglobulin light chains or serum amyloid A–related protein and, less commonly, mutated forms of apolipoproteins AI or AII, lysozyme, fibrinogen, gelsolin, or transthyretin. Study Design Case series. Setting & Participants 10 patients with renal amyloidosis who had an amyloidogenic protein that was not identified using routine immunohistochemistry. Outcomes Clinical, pathologic, biochemical, and genetic characteristics. Measurements Tandem mass spectrometry was used to analyze fibrils extracted from sections of formalin-fixed paraffin-embedded amyloid-containing kidney biopsy specimen blocks. Results Chemical analyses showed peptides corresponding to the carboxy-terminal portion of the leukocyte Chemotactic Factor 2 (LECT2) molecule. In addition, deposits were immunostained using an anti–human LECT2 monoclonal antibody. Plasma specimens were available from 2 individuals for whom LECT2 concentration in these samples was within the reference range. Additionally, in 4 of the cases analyzed at the molecular level, isolation of genomic DNA and polymerase chain reaction amplification of LECT2-encoding exons showed no mutations. However, all were homozygous for the G allele encoding valine at position 40 in the mature protein, a finding confirmed using restriction enzyme analysis of the polymorphic site. Limitations Causality is not addressed. Conclusions Based on our studies, we posit that LECT2-associated renal amyloidosis represents a unique and perhaps not uncommon disease, especially in Mexican Americans. The pathogenesis, extent, and prognosis remain to be determined.

  • prevalence and morphology of leukocyte Chemotactic Factor 2 associated amyloid in renal biopsies
    Kidney International, 2010
    Co-Authors: Christopher P. Larsen, Deborah T. Weiss, Patrick D Walker, Alan Solomon
    Abstract:

    Renal pathologists identify the protein component of renal amyloid deposits by immunohistochemistry using antibodies against known amyloidogenic proteins. The majority of amyloid cases can be categorized by a simple antibody panel that includes immunoglobulin light chains lambda and kappa, and serum amyloid A. In some instances, however, these reagents do not recognize materials that stain with Congo red or yield ambiguous staining results, thus creating a diagnostic dilemma. Chemical analysis of fibrils extracted from such a nonreactive renal biopsy led to the discovery of a previously unknown amyloid formed from leukocyte Chemotactic Factor 2 (LECT2). Over the past 8 years, we received 285 renal amyloid samples, of which 31 remained unclassified. In an effort to determine whether any of the latter samples were LECT2 related, tandem mass spectrometry was performed. In all, 7 of the 31 cases were identified as an amyloid LECT2 (ALECT2), a finding confirmed immunohistochemically using a LECT2-specific antibody. The deposits strongly stained for Congo red and, in most cases, had distinctive morphological features with diffuse involvement of the interstitium, arteries, and glomeruli. Hence, we believe that ALECT2 represents the third common form of renal amyloidosis.

John H. Walsh - One of the best experts on this subject based on the ideXlab platform.

  • Diethyl phthalate, a Chemotactic Factor secreted by Helicobacter pylori.
    The Journal of biological chemistry, 2001
    Co-Authors: David A. Keire, Peter A. Anton, Kym F. Faull, E. Ruth, John H. Walsh, Peter Chew, Demey Quisimoro, Mary C. Territo, Joseph R. Reeve
    Abstract:

    Abstract The structure of a small-molecule, non-peptide Chemotactic Factor has been determined from activity purified to apparent homogeneity from Helicobacter pylori supernatants.H. pylori was grown in brucella broth media until one liter of solution had 0.9 absorbance units. The culture was centrifuged, and the bacteria re-suspended in physiological saline and incubated at 37 °C for 4 h. A monocyte migration bioassay revealed the presence of a single active Chemotactic Factor in the supernatant from this incubation. The Chemotactic Factor was concentrated by solid phase chromatography and purified by reverse phase high pressure liquid chromatography. The Factor was shown to be indistinguishable from diethyl phthalate (DEP) on the basis of multiple criteria including nuclear magnetic resonance spectroscopy, electron impact mass spectroscopy, UV visible absorption spectrometry, GC and high pressure liquid chromatography retention times, and Chemotactic activity toward monocytes. Control experiments with incubated culture media without detectable bacteria did not yield detectable DEP, suggesting it is bacterially derived. It is not known if the bacteria produce diethyl phthalate de novo or if it is a metabolic product of a precursor molecule present in culture media. DEP produced by H. pylori in addition to DEP present in man-made products may contribute to the high levels of DEP metabolites observed in human urine. DEP represents a new class of Chemotactic Factor.

  • helicobacter pylori secretes a Chemotactic Factor for monocytes and neutrophils
    Gut, 1992
    Co-Authors: P M Craig, M C Territo, William E Karnes, John H. Walsh
    Abstract:

    Helicobacter pylori is associated with an inflammatory reaction in the stomach and duodenum, yet the mechanism of this inflammatory infiltrate is unknown. The ability of Helicobacter pylori to secrete a Factor that attracts leucocytes is investigated. Helicobacter pylori conditioned supernatant attracted neutrophils and monocytes with 50-100% of the activity of control Chemotactic Factor, 10(-8) M formyl-methionine-leucine-phenylalanine. Strains derived from individuals with ulcer or non-ulcer associated H pylori infections displayed similar Chemotactic activity. Preliminary characterisation shows that the Factor has a molecular weight of less than 3000, is heat stable, is acid resistant, and can be diluted at least 10-fold. Checkerboard analysis confirmed that the activity was Chemotactic rather than chemokinetic. This Chemotactic activity could play a role in the pathogenesis of Helicobacter pylori gastritis.

Patrick D Walker - One of the best experts on this subject based on the ideXlab platform.

  • clinical morphologic and genetic features of renal leukocyte Chemotactic Factor 2 amyloidosis
    Kidney International, 2014
    Co-Authors: Christopher P. Larsen, Alan Solomon, Robert J Kossmann, Marjorie L Beggs, Patrick D Walker
    Abstract:

    Leukocyte Chemotactic Factor 2 amyloidosis (ALECT2) is a recently described form of amyloidosis that most frequently manifests clinically with progressive renal failure. In a series of 414 cases of amyloidosis, there were 40 cases of ALECT2: the second most common type of renal amyloidosis in this series. This was particularly common in Hispanic patients in the Southwest United States, where more than half of amyloidosis cases were ALECT2. It is possible that this represents a familial amyloidosis as there were two brothers with ALECT2 in our study. Morphologically, there was consistent amyloid deposition in the renal cortex with medullary involvement in only about a third of cases. There were no mutations detected in the LECT2 gene, although all patients tested were homozygous for the G nucleotide in a non-synonymous SNP at position 172. Most patients presented with chronic kidney disease and, on follow-up, showed progression with an average deterioration in renal function of 0.5ml/min/1.73m 2 per month. Unfortunately, the etiology of ALECT2 is currently unknown and there is currently no efficacious treatment of the disease.

  • prevalence and morphology of leukocyte Chemotactic Factor 2 associated amyloid in renal biopsies
    Kidney International, 2010
    Co-Authors: Christopher P. Larsen, Deborah T. Weiss, Patrick D Walker, Alan Solomon
    Abstract:

    Renal pathologists identify the protein component of renal amyloid deposits by immunohistochemistry using antibodies against known amyloidogenic proteins. The majority of amyloid cases can be categorized by a simple antibody panel that includes immunoglobulin light chains lambda and kappa, and serum amyloid A. In some instances, however, these reagents do not recognize materials that stain with Congo red or yield ambiguous staining results, thus creating a diagnostic dilemma. Chemical analysis of fibrils extracted from such a nonreactive renal biopsy led to the discovery of a previously unknown amyloid formed from leukocyte Chemotactic Factor 2 (LECT2). Over the past 8 years, we received 285 renal amyloid samples, of which 31 remained unclassified. In an effort to determine whether any of the latter samples were LECT2 related, tandem mass spectrometry was performed. In all, 7 of the 31 cases were identified as an amyloid LECT2 (ALECT2), a finding confirmed immunohistochemically using a LECT2-specific antibody. The deposits strongly stained for Congo red and, in most cases, had distinctive morphological features with diffuse involvement of the interstitium, arteries, and glomeruli. Hence, we believe that ALECT2 represents the third common form of renal amyloidosis.

U. C. Chaturvedi - One of the best experts on this subject based on the ideXlab platform.