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"Shapiro, John"
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War in the ring : Joe Lewis, Max Schmeling, and the fight between America and Hitler
\"...recount[s] the politically and racially charged rivalry between African-American boxing champion Joe Louis and white German boxer Max Schmeling, which grew between their 1936 and 1938 matches. Tracing both men's careers from inception until they hung up their gloves, the authors illuminate how emblematic each was to his country while exploring the social issues of the day.\"-- Publisher's description.
Book
Plasma proteomics of acute tubular injury
The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ’s metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (
n
= 44), the Atherosclerosis Risk in Communities (ARIC) study (
n
= 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (
n
= 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.
Acute tubular injury (ATI) significantly contributes to many kidney diseases. Here, the authors identify several immune response and cellular stress plasma proteins linked to ATI severity and acute kidney injury, which may aid in non-invasive ATI assessment.
Journal Article
Marked man : Frank Serpico's inside battle against police corruption
\"Marked Man tells the propulsive story of Frank Serpico who, in the 1960s, single-handedly rooted out systematic corruption in the New York Police Department. Since the NYPD was formed in 1845, the famous \"pad\" was as much a criminal ring as it was a legitimate police force. As the decades wore on, corruption became so out of hand that cops were regularly demanding payments from brothels, bars, pool halls, and gambling joints to keep them out of trouble with the law. It was a multimillion-dollar-a-year business that everyone seemed to turn a blind eye to. Everyone, that is, except Frank Serpico. Delve into this true story of corruption and greed, of the dark history of the largest police department in the US, and the price one man pays for doing what he thinks is right. Perfect for fans of Steve Sheinkin and Rebecca Barone, Marked Man is a dive into one man's courageous fight against a corrupt system\"-- Provided by publisher.
Book
Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study
Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC–MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups—SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN—mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
Journal Article
Characterization of glomerular diseases using proteomic analysis of laser capture microdissected glomeruli
The application of molecular techniques to characterize clinical kidney biopsies has the potential to provide insights into glomerular diseases that cannot be revealed by traditional renal pathology. The present work is a proof-of-concept approach to test whether proteomic analysis of glomeruli isolated from clinical biopsies by laser capture microdissection can provide unique information regarding differentially expressed proteins relevant to disease pathogenesis. The proteomes of glomeruli isolated by laser capture microdissection from biopsies of normal kidneys (living-related donor kidneys) were compared with those from patients with diabetic nephropathy, lupus nephritis, and fibronectin glomerulopathy. Glomerular proteins were extracted, trypsin digested, and subjected to liquid chromatography–tandem mass spectrometry for identification and quantitation. Relative to normal glomeruli, all disease-associated glomeruli showed an increased presence of complement components, a marked decline in podocyte-associated proteins, and a decrease in proteins associated with cellular metabolism. Additionally, fibronectin glomerulopathy glomeruli differed from all the other glomeruli because of a significant accumulation of fibronectin and fibulin. This study demonstrates that our method acquires reproducible and quantitative proteomic information from laser capture microdissection isolates that can be used to characterize the molecular features of glomerular diseases.
Journal Article
Fast track : a legal, historical, and political analysis
\"Fast Track is the story of the rise and fall of U.S. leadership in international trade. Fast Track authority is the process Congress devised to approve trade agreements, giving Congress input into negotiations in exchange for a timely up-or-down vote. Foes derided it as a procedural gimmick, but it helped forge a bipartisan consensus on trade policy. Despite its successes, it was also fragile. The bipartisan consensus has since frayed and Fast Track has lapsed, allowing other countries to fill the void. This book discusses how Fast Track worked and offers a path for rebuilding consensus in favor of its renewal\"-- Provided by publisher.
BOOK
A Novel Inflammatory Dendritic Cell That Is Abundant and Contiguous to T Cells in the Kidneys of Patients With Lupus Nephritis
The mechanisms that promote local inflammatory injury during lupus nephritis (LN) flare are largely unknown. Understanding the key immune cells that drive intrarenal inflammation will advance our knowledge of disease pathogenesis and inform the development of new therapeutics for LN management. In this study, we analyzed kidney biopsies from patients with proliferative LN and identified a novel inflammatory dendritic cell (infDC) population that is highly expressed in the LN kidney, but minimally present in healthy human kidneys. During an agnostic evaluation of immune transcript expression in the kidneys of patients with proliferative LN, the most abundantly overexpressed transcript from isolated glomeruli was FCER1G , which encodes the Fc receptor gamma chain (FcRγ). To identify the cell types expressing FcRγ that infiltrate the kidney in LN, studies were done on kidney biopsies from patients with active LN using confocal immunofluorescence (IF) microscopy. This showed that FcRγ is abundantly present in the periglomerular (PG) region of the kidney and to a lesser extent in the tubulointerstitium (TI). Further investigation of the surface markers of these cells showed that they were FcRγ + , MHC II + , CD11c + , CD163 + , CD5 − , DC-SIGN + , CD64 + , CD14 + , CD16 + , SIRPα + , CD206 − , CD68 − , CD123 − , CD3 − , and CD11b − , suggesting the cells were infDCs. Quantification of the infDCs showed an average 10-fold higher level of infDCs in the LN kidney compared to the healthy kidneys. Importantly, IF identified CD3 + T cells to be adjacent to these infDCs in the PG space of the LN kidney, whereas both cell types are minimally present in the healthy kidney. Thus, we have identified a previously undescribed DC in lupus kidneys that may interact with intrarenal T cells and play a role in the pathogenesis of kidney injury during LN flare.
Journal Article
Protection from Fas-Mediated Apoptosis by a Soluble Form of the Fas Molecule
Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. Molecular cloning and nucleotide sequence analysis revealed a human Fas messenger RNA variant capable of encoding a soluble Fas molecule lacking the transmembrane domain because of the deletion of an exon encoding this region. The expression of soluble Fas was confirmed by flow cytometry and immunocytochemical analysis. Supernatants from cells transfected with the variant messenger RNA blocked apoptosis induced by the antibody to Fas. Levels of soluble Fas were elevated in patients with systemic lupus erythematosus, and mice injected with soluble Fas displayed autoimmune features.
Journal Article
SARPs: A Family of Secreted Apoptosis-Related Proteins
Quiescent mouse embryonic C3H/10T1/2cells are more resistant to different proapoptotic stimuli than are these cells in the exponential phase of growth. However, the exponentially growing 10T1/2cells are resistant to inhibitors of RNA or protein synthesis, whereas quiescent cells die upon these treatments. Conditioned medium from quiescent 10T1/2cells possesses anti-apoptotic activity, suggesting the presence of protein(s) that function as an inhibitor of the apoptotic program. Using differential display technique, we identified and cloned a cDNA designated sarp1 (secreted apoptosis-related protein) that is expressed in quiescent but not in exponentially growing 10T1/2cells. Hybridization studies with sarp1 revealed two additional family members. Cloning and sequencing of sarp2 and sarp3 revealed 38% and 40% sequence identity to sarp1, respectively. Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli. Expression of sarp family members is tissue specific. sarp mRNAs encode secreted proteins that possess a cysteine-rich domain (CRD) homologous to the CRD of frizzled proteins but lack putative membrane-spanning segments. Expression of SARPs modifies the intracellular levels of β -catenin, suggesting that SARPs interfere with the Wnt-frizzled proteins signaling pathway.
Journal Article