tbuckley/cabot-search huggingface dataset:
The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon
Authors: Xiao-Yan Wang, Shyama Masilamani, Jakob Nielsen, Tae-Hwan Kwon, Heddwen L. Brooks, Søren Nielsen, Mark A. Knepper
Journal: Journal of Clinical Investigation (2001)

The kidneys “escape” from the Na-retaining effects of aldosterone when circulating levels of aldosterone are inappropriately elevated in the setting of normal or expanded extracellular fluid volume, e.g., in primary aldosteronism. Using a targeted proteomics approach, we screened renal protein extracts with rabbit polyclonal antibodies directed to each of the major Na transporters expressed along the nephron to determine whether escape from aldosterone-mediated Na retention is associated with decreased abundance of one or more of renal Na transporters. The analysis revealed that the renal abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) was profoundly and selectively decreased. None of the other apical solute-coupled Na transporters displayed decreases in abundance, nor were the total abundances of the three ENaC subunits significantly altered. Immunocytochemistry showed a strong decrease in NCC labeling in distal convoluted tubules of aldosterone-escape rats with no change in the cellular distribution of NCC. Ribonuclease protection assays (RPAs) revealed that the decrease in NCC protein abundance was not associated with altered NCC mRNA abundance. Thus, the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule appears to be the chief molecular target for regulatory processes responsible for mineralocorticoid escape, decreasing in abundance via a posttranscriptional mechanism.
RARE-30. CASE SERIES OF INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR: A SINGLE INSTITUTION EXPERIENCE
Authors: Nidhi Shah, Andrew Walter
Journal: Neuro-Oncology (2018)

Intracranial non-germinomatous germ cell tumors are a rare, heterogenous group of neoplasms, commonly occurring in the pineal and/or suprasellar regions. The subtypes include yolk sac tumor (YST) or endodermal sinus tumor (EST), embryonal carcinoma (EC), choriocarcinoma (CHC), and mixed malignant subtypes. Diagnosis is usually made without a biopsy, through detection of elevated levels of Alpha-fetoprotein (AFP) and/or beta-human chorionic gonadotropin (βHCG) in the serum and/or cerebrospinal fluid. Three patients with intracranial NGGCT were treated at our institution, using a combination of surgery, chemotherapy, and/or radiation therapy. The clinical presentation of all cases included signs and symptoms of obstructive hydrocephalus. Patient #1 was diagnosed with malignant teratoma at birth via neuroimaging; she died from complications due to surgical resection. Patient #2 was diagnosed with choriocarcinoma of the pituitary gland at age 5 years via elevated AFP in serum and CSF; he was treated with alternating cycles of carboplatin/etoposide and ifosfamide/etoposide, followed by whole ventricle radiation therapy. He is now 28 months off-therapy, without evidence of disease. Patient #3 was diagnosed with choriocarcinoma of the pineal and suprasellar regions at the age 7 years, via elevated beta-HCG in serum and CSF, with evidence of bimodal disease. Treatment included 6 cycles of risk-adapted chemotherapy followed by whole ventricle radiation therapy. Neuroimaging continues to show no evidence of disease with normalization of tumor markers, at 24 months off-therapy. Patients #2 and #3 have residual neuroendocrine and neuropsychological deficits, but remain neurodevelopmentally appropriate. Combination of chemotherapy and radiation therapy is required for optimal prognosis.
Editorial: Management of osteoporosis.
Journal: BMJ (1975)

Management of osteoporosisEver since Albright and his colleagues' drew attention to the association between the menopause and spinal osteoporosis oestrogens have been widely used in the management of post- menopausal bone disease.Despite the theoretical value of such treatment, satisfactory evidence of its practical benefits has proved difficult to obtain.Davis et a12 and Meema and Meema3
HONESTY IN EXPERIMENTAL RESEARCH.
Journal: JAMA (1992)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
In situ detection of lipid peroxidation by-products in chronic liver diseases
Authors: V Paradis, M Kollinger, M Fabre, A Holstege, T Poynard, P Bedossa
Journal: Hepatology (1997)

Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. The deleterious consequences of this mechanism are related in part to the formation of reactive aldehydic products that bind to intra- or extracellular molecules to form adducts. Specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, allowed us to investigate in situ, with an immunohistochemical procedure, the occurrence of lipid peroxidation in a panel of different chronic liver diseases. Intracellular HNE and MDA adducts were detected respectively in 24 of 39 cases (62%) and in 12 of 34 cases investigated (35%). They were localized mainly in the cytoplasm of hepatocytes, with the strongest staining observed in hemochromatosis, Wilson's disease, and in areas of acute alcoholic hepatitis in cases of alcoholic liver diseases. A peculiar pattern of immunostaining was observed in primary biliary cirrhosis where biliary cells of destroyed but also intact bile ducts strongly expressed HNE adducts. The liver extracellular matrix also displayed MDA adducts (30 of 34 cases, 88%) and HNE adducts (23 of 39 cases, 59%). While HNE adducts were specifically localized on large bundles of collagen fibers, MDA adducts were detected in a thin reticular network and in sinusoidal cells around portal tracts or fibrous septa. In conclusion, lipid peroxidation by-products are detectable in chronic liver diseases. Immunohistochemical results suggest that this mechanism is implicated very early in the pathogenesis of some of these diseases.
X-rays and breast cancer
Authors: J. W. Gofman
Journal: JAMA (1995)

<h3>To the Editor.</h3> —My estimate that at least 75% of current breast cancer in the United States is due to earlier medical irradiation<sup>1</sup>was called a 12-fold overestimate in the article by Mr Skolnick.<sup>2</sup>He is quoting Clark Heath of the American Cancer Society, who asserts that I made "two serious errors." First, an alleged twofold overestimate comes from my "assumption" that dose response is supralinear. This is no assumption. The human evidence from the survivors of the atomic bomb for all cancers combined shows supralinearity fitting the observations provably better than linearity.<sup>3</sup>Supralinearity specifically for breast cancer is visible to anyone who inspects the figure on page S26 of Thompson et al,<sup>4</sup>although the analysis by Land<sup>5</sup>raises questions. Second, an alleged sixfold overestimate comes from transport of Japanese evidence to the United States. Why did I not use North American data? Because (1)
The Medicine of the Future
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Tumor microenvironment (TME), longitudinal biomarker changes, and clinical outcome in patients (pts) with advanced <i>BRAF</i> V600–mutant melanoma treated with first-line spartalizumab (S) + dabrafenib (D) + trametinib (T).
Authors: Reinhard Dummer, Daniel Gusenleitner, Catarina D. Campbell, Celeste Lebbe, Victoria Atkinson, Mario Mandalà, Paul D. Nathan, Ana Arance, Erika Richtig, Naoya Yamazaki, Caroline Robert, Dirk Schadendorf, Hussein Abdul-Hassan Tawbi, Paolo Antonio Ascierto, Antoni Ribas, Keith Flaherty, Eduard Gasal, Jan C. Brase, Georgina V. Long
Journal: Journal of Clinical Oncology (2020)

39 Background: Although pts with both low tumor mutation burden (TMB) and T-cell–inflamed gene expression profiles (TI-GEPs) usually have poor outcomes with anti–PD-1 therapy, an analysis in the adjuvant melanoma setting suggested that these pts benefited from adjuvant D+T therapy. Here we analyze TMB/TI-GEPs and other biomarkers in pts receiving a combination of anti–PD-1 and D+T therapy. Methods: The phase 3 COMBI-i study (NCT02967692) is evaluating S in combination with D+T in previously untreated pts with BRAF V600–mutant unresectable/metastatic melanoma. In the safety run-in (part [p] 1) and biomarker (p2) cohorts, blood/tissue samples were collected at baseline (BL), after 2-3 and 8-12 wk of treatment, and at disease progression. TMB/circulating tumor DNA (ctDNA) and TI-GEPs were examined by targeted DNA-seq and RNA-seq, respectively. Results: At data cutoff, 6 of 22 pts with DNA- and RNA-seq data available had a PFS event. At BL, these pts had low TMB, low TI-GEPs (4 of 6), or high levels of immunosuppressive TME signatures (eg, fibroblast, M2 macrophages) vs pts without a PFS event. Elevated BL ctDNA was significantly associated with PFS events ( P&lt; .001). Pts with a complete response (CR) on S+D+T had significantly lower levels of BL immunosuppressive TME signatures (eg, M2 macrophages; P&lt; .01) than pts without a CR. We observed a consistent increase in TI-GEPs and decrease in MAPK pathway activity score (MPAS) from BL to biopsy at 2-3 wk in all pts regardless of subsequent progression. Pts with a PFS event and available longitudinal biomarker data were characterized by a subsequent decrease in TI-GEPs and an increase in MPAS per the 8- to 12- wk biopsy sample. Conclusions: These results suggest that S+D+T had an early impact on tumor cells and the TME, potentially promoting antitumor activity. The majority of PFS events occurred in the TMB-low/TI-GEP-low subgroup. An immunosuppressive TME might preclude early CRs. The predictive implications of coupling TMB/GEP subgroups with other TME marker subgroups need further validation. The randomized placebo-controlled p3 of COMBI-i is ongoing. Clinical trial information: NCT02967692.
Vancomycin-Resistant Staphylococcus aureus--Pennsylvania, 2002
Journal: JAMA (2002)

Staphylococcus aureus is one of the most common causes of hospital- and community-acquired infections. Since the recognition of vancomycin-resistant enterococci in 1988, the emergence of vancomycin-resistant S. aureus (VRSA) (minimum inhibitory concentration [MIC] > or = 32 microg/mL) has been anticipated. The transfer of the genetic element containing the vanA vancomycin resistance gene from Enterococcus faecalis to S. aureus was demonstrated in the laboratory in 1992; the first clinical infection with VRSA was reported in July 2002. This report describes the second documented clinical isolate of VRSA from a patient.
Incorrect Test Name
Journal: JAMA (1983)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Allergy abstracts
Authors: David Stein Suffern, Andre Codisf'oti, Bernard Siegel, Brooklyn Cleveland, Juana Phillipp, Neil Goldman, Yorktown Heighrs, Mandakolathur Mural, ! Br<wk, ! \ri "v K' Monroe, Coleman Stamford, Eugene Walzer, Bridgeport Corm, N Sheldon Berger Freehold
Journal: Journal of Allergy and Clinical Immunology (1981)
Abstract 1972: CXCR5-CXCL13 signaling contributes to CLL relapse and patient survival
Authors: Tiara Griffen, Corey Young, Courtney D. Dill, Kaylin Carey, Olayinka Adebayo, Sha'kayla Nunez, James Lillard
Journal: Cancer Research (2019)

Abstract Chronic Lymphocytic Leukemia (CLL) is characterized by the appearance of mature-appearing B cells in the blood, bone marrow, and secondary lymphoid organs. There is an average of 19,000 new cases, in the United States annually, but the molecular pathogenesis of CLL is incompletely understood. Chemokines and their receptors have been shown to contribute to the progression and metastasis of several types of cancers. Chemokine receptor 5 (CXCR5) and chemokine ligand 13 (CXCL13) are produced by cells in the microenvironment of secondary lymphoid organs such as lymphatic endothelial cells, which promote disease progression. There is a gap in understanding the molecular mechanisms and functions resulting from CXCL13-CXCR5 interactions during CLL. This gap is important to fill, because these molecules could be additional therapeutic targets to treat this disease. Together this provided the rationale to test the hypothesis CXCR5-CXCL13 signaling contributes to the growth, metastasis, and survival of CLL. The role of CXCR5, CXCL13, and associated genes was determined by conducting Weighted Gene Network Co-expression (WGCNA) and upstream regulator, canonical pathway, and gene interaction analyses of 297 International Cancer Genome Consortium (ICGC) CLL patients. Our previous studies show CXCR5-CXCL13 signaling activates CTNNB1, JUN, and VAV2 transcriptional factors. These factors promote the expression of GNA, GRK, PIK3, RAC and RHO family genes, which were significantly associated with the WGCNA-designated Yellow signaling module. Interestingly, the WGCNA-designated Grey module contained independently expressed genes, e.g., CXCL13, LTB, IGHV, ZAP70, which were significantly associated (p = 0.00003) and correlated (R2 = 0.29) with relapse. Genes in this module significantly correlated with CLL relapse and survival. Taken together, our data demonstrate the clinical significance of the CXCL13-CXCR5 pathway in CLL progression. Citation Format: Tiara Griffen, Corey Young, Courtney D. Dill, Kaylin Carey, Olayinka Adebayo, Sha'kayla Nunez, James Lillard. CXCR5-CXCL13 signaling contributes to CLL relapse and patient survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1972.
Effects of Lead on the Kidney: Roles of High-Affinity Lead-Binding Proteins
Authors: Bruce A. Fowler, George DuVal
Journal: Environmental Health Perspectives (1991)

Lead-induced nephropathy produces both tubular and interstitial manifestations of cell injury, but the pathophysiology of these lesions is not completely understood. Delineation of the molecular factors underlying renal handling of lead is one of central importance in understanding the mechanisms of renal cell injury from this agent. Recent studies from this laboratory have identified several distinct high-affinity lead-binding proteins (PbBP) from rat kidney and brain that appear to play critical roles in the intracellular bioavailability of lead to several essential cellular processes in these target tissues at low dose levels. The PbBP from rat kidney has been shown to be a specific cleavage product of alpha 2-microglobulin, which is a member of the retinol-binding protein superfamily. Recent preliminary Western blot and immunohistochemical studies have shown that a polyclonal antibody to the renal PbBP does not recognize the brain PbBP, which appears to be a chemically similar, but distinct molecule. These studies have also shown that the renal PbBP is selectively localized in only certain nephrons and only specific segments of the renal proximal tubule. The striking nephror and cell-type specificity of the localization reaction could result from physiological differences in nephron functional activity or selective molecular uptake mechanisms/metabolism differences that act to define target cell populations in the kidney. In addition, other preliminary studies have shown that short-term, high-dose lead exposure produces increased excretion of this protein into the urine with concomitant decreases in renal concentrations.
In This Issue
Journal: Journal of Clinical Investigation (2008)

How 13-cis retinoic acid combats acne 13-cis retinoic acid (13-cis RA; also known as isotretinoin) is the most potent agent available for the treatment of acne.Use of the drug is limited due to teratogenic side effects, however, and there is no available alternative with comparable efficacy.Little is known about the mechanism by which 13-cis RA treats acne, but it is hoped that understanding this mechanism will lead to development of a therapeutic alternative to this drug.In this issue, Nelson and colleagues (pages 1468-1478) have described that 13-cis RA induces apoptosis in human sebaceous glands in vivo and that this effect is mediated by increased expression of the gene lipocalin 2, which encodes neutrophil gelatinase-associated lipocalin (NGAL).The authors found increased immunolocalization of NGAL in the sebaceous glands of individuals with acne following treatment with 13-cis RA.Recombinant NGAL also induced apoptosis in cells cultured from human sebocytes.Furthermore, apoptosis in response to 13-cis RA was inhibited in the presence of siRNA to lipocalin 2. These data led the authors to suggest that the apoptotic effect of 13-cis RA is mediated by NGAL and that agents that selectively induce NGAL expression in human sebaceous glands might provide a new approach to treating individuals with acne.
PWE-130 Effect Of N Acetylcysteine (NAC) in Hypoxia Induced Liver Injury (HILI)–A Randomized Placebo Control Clinical Trial
Authors: P Basu, N J Shah, S Farhat, R Siriki, K Mittimanj, M Rahaman, S Atluri
Journal: Gut (2013)

<h3>Introduction</h3> HILI is common with a prevalence of 10% in US. Transient shift of intra hepatic hemodynamic compromise leads to tissue hypoxia and induces hypoxia induced protein (HIP), heat shock protein 70 (HSP24.70), Endothelial reticular stress (ER) leading to reperfusion injury (RI). Dramatic rise of transaminases, drastic reversal with restoration of perfusion in weeks follows. In cirrhotics HILI requires liver transplantation. This study evaluated spontaneous recovery and salvage in HILI utilising NAC. <h3>Methods</h3> Sixty patients (n = 60) with mean arterial pressure (MAP) &lt; 35% and normal LFTs at base line. Group A (n = 28) chronic liver disease (CLD) [alcohol-11/28 (39%), NASH-9/28 (32%), Hepatitis C-4/28 (14%), hepatitis B-2/28 (7%), PBC-1/28 (3%), AIH-1/28 (3%). Group B (n = 32) [respiratory failure-12/32 (37%), CHF-8/32 (25%), CVA-2/32 (6%), sepsis-6/32 (19%), post op-4/32 (12%)]. Randomized into Placebo group- A1 (14) &amp; B1 (16) and IV NAC for 48 hours - A2 (14) &amp; B2 (16). Serum Transaminases, Bilirubin, INR, Creatinine and MELD score at 0, 3rd, 6th, 9th and 12th days with MAP and modified Sequential Organ Failure Assessment (SOFA) Score. All patients were allowed standard of care (SOC) and resuscitations if needed. Exclusions: Organ transplant, Septic shock, Hemodialysis, cancer, acute myocardial Infarct, Tylenol injury, acute viral hepatitis and organ trauma. <h3>Results</h3> Placebo groups A1, B1: Normalized A1-[LFTs- on 3rd day-(7%), 6th day-(21%), 9th day-(36%) and 12th day-(21%). 1/14(7%) died]. B1(CLD)[ LFTs 3rd day-(19%) 6th (44%) 9 th (25%),2/16(6%) died of sepsis] NAC Groups A2[normalised LFTs 3rd (57%)6th day-(43%) 9 th day (25%), (7%)-one died ] B2 (CLD)[Normalized LFTs- 3rd day-(63%), 6th day-(25%) 9 th1/16(6%), one died] <h3>Conclusion</h3> This Study postulates that IV NAC (A2, B2) has efficient spontaneous recovery and salvage in non-CLD sub group B2 (63%) &gt; A2(57%) in day 3, in CLD NAC (A2) &gt; placebo (A1) clinical recovery over placebo at 3rd day, (44%) over (36%) - 6th day. Larger trial need to establish the routine usage of IV NAC in HILI. <h3>Disclosure of Interest</h3> None Declared.
Transactions of the New York State Medical Association for 1888. Vol. v.
Journal: JAMA (1889)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal