tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Cost-Effectiveness of Prasugrel Versus Clopidogrel in Patients With Acute Coronary Syndromes and Planned Percutaneous Coronary Intervention: Results From the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction TRITON-TIMI 38”
Authors: Elizabeth M. Mahoney, Kaijun Wang, Suzanne V. Arnold, David J. Cohen, Irina Proskorovsky, Stephen Wiviott, Elliott Antman, Eugene Braunwald
Journal: Circulation (2010)
Renal Excretion of Potassium
Authors: Clifton K. Meador
Journal: JAMA (1968)

To the Editor:—  W. D. Snively, MD, in a recent editorial entitled An Example of Atavistic Physiology?, expressed opinions concerning the appropriateness of the renal mechanism for handling sodium and potassium (204:392, 1968). While it is unlikely that this or any discussion will change the order of things, his statement that civilized man's present pattern has outlasted its usefulness can be questioned.  Dr. Snively states that man's kidney can conserve sodium avidly, but, that it wastes  This is only when the intake of the ions is brought virtually to zero. From results of experiments of extreme deprivation, he extrapolates to conclude, Clearly, the body manifests an inappropriate, even damaging, pattern of hoarding sodium and wasting potassium. Under conditions usually met in nature, these renal responses to sodium or potassium withdrawal are quite appropriate and life saving. The extracellular space with its life-maintaining plasma volume is appropriately protected by
Abstract LB-102: A tumor-specific tissue penetrating peptide inhibits metastasis
Authors: Kazuki N. Sugahara, Gary B. Braun, Tatiana H. de Mendoza, Venkata R. Kotamraju, Tambet Teesalu, Erkki Ruoslahti, Randall P. French, Andrew M. Lowy
Journal: Cancer Research (2014)

Abstract Neuropilin-binding tumor-penetrating peptides increase vascular and tissue permeability in tumors, allowing drugs conjugated to the peptide and even free drugs co-injected with the peptide to widely distribute within the tumor tissue (Sugahara KN et al, Cancer Cell 16:510, 2009; Science 328:1031, 2010). Thus, the peptides provide an elegant way to enhance therapeutic index of anti-cancer drugs. However, the ability of the peptides to increase vascular permeability has raised concerns that the peptides might enhance metastasis by promoting cell seeding from the primary tumor. Here, we show a recent unexpected finding that a prototypic tumor-penetrating peptide, iRGD (amino acid sequence: CRGDK/RGPD/EC), is a potent metastasis inhibitor. iRGD did not cause systemic tumor cell dissemination or metastasis in mice bearing breast tumors with low metastatic potential. iRGD treatment of mice bearing aggressive orthotopic pancreatic tumors resulted in significant decrease in spontaneous metastasis formation. Primary tumor growth was not affected by the treatment. Another tumor-penetrating peptide, iNGR, also inhibited metastasis, while conventional RGD peptides or a scrambled iRGD peptide that lack neuropilin affinity failed to do. These results indicate that the anti-metastatic effect of iRGD was dependent on its neuropilin-binding peptide motif. In vitro migration assays demonstrated that iRGD potently inhibits tumor cell migration and serves as a chemorepellent of tumor cells in a neuropilin-dependent manner. Chemorepulsion assays based on live cell imaging confirmed the findings, and further demonstrated that iRGD dramatically collapses tumor cell protrusions leading to an instantaneous retraction of tumor cells from iRGD-bound surfaces. Our finding refutes the hypothesis that iRGD may cause enhanced metastasis. The mechanism of the anti-metastatic effect may involve neuropilin-mediated chemorepulsion of tumor cells. Collectively, iRGD may simultaneously achieve tumor-specific drug delivery and metastasis inhibition when utilized for cancer treatment. Citation Format: Kazuki N. Sugahara, Gary B. Braun, Tatiana H. de Mendoza, Venkata R. Kotamraju, Tambet Teesalu, Erkki Ruoslahti, Randall P. French, Andrew M. Lowy. A tumor-specific tissue penetrating peptide inhibits metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-102. doi:10.1158/1538-7445.AM2014-LB-102
Detection of cytokine-induced protein γ-immune protein-10 (γ-IP10) in atypical melanocytic proliferations
Authors: Bruce R. Smoller, James Krueger
Journal: Journal of the American Academy of Dermatology (1991)

gamma-Immune protein-10 (gamma-IP10) is a cytokine whose expression has been shown to be induced by interferon-gamma. It is a member of a group of closely related cytokines (e.g., interleukin 8 and platelet factor 4) with chemotactic properties. gamma-IP10 has been detected in keratinocytes, lymphocytes, monocytes, and endothelial cells in immunologically mediated processes, such as positive tuberculin skin tests, and in growth-activated keratinocytes, such as in psoriasis. Keratinocytes in normal epidermis do not produce gamma-IP10. We tested the hypothesis that keratinocytes adjacent to dysplastic nevi and melanomas would produce gamma-IP10, perhaps as part of an immune response to a tumor, and that this response would not be seen in ordinary melanocytic nevi. We used an affinity-purified, polyclonal rabbit anti-gamma-IP10 antibody to examine 10 nevi with moderate to severe histologic dysplasia, one superficial spreading melanoma, and 10 compound melanocytic nevi with no features of dysplasia. As predicted, keratinocytes surrounding all of the cytologically atypical melanocytic lesions displayed strong staining with gamma-IP10. There was no staining of keratinocytes adjacent to ordinary melanocytic nevi. The observed keratinocyte staining with gamma-IP10 may be related to a host immune response to antigenically abnormal cells.
Human placenta sphingomyelinase, an exogenous acidic pH-optimum sphingomyelinase, induces oxidative stress, glutathione depletion, and apoptosis in rat hepatocytes
Authors: Carmen García-Ruiz, Montse Marí, Albert Morales, Anna Colell, Esther Ardite, José C. Fernández-Checa
Journal: Hepatology (2000)

Ceramide has been identified as a putative lipid messenger that mediates diverse cellular processes including cell death. Since glutathione (GSH) depletion is known to sensitize cells to many cytotoxic agents and as a result of the reported regulation of neutral sphyngomyelinase (NSMase) by GSH, the present study compared the role of individual SMases in the induction of oxidative stress, regulation of cellular GSH, and apoptosis of rat hepatocytes. Exposure of cultured rat hepatocytes to exogenous Bacillus cereus sphingomyelinase (bSMase), a neutral SMase, or human placenta sphingomyelinase (hSMase), an acidic SMase (ASMase), generated similar ceramide levels in a dose-dependent manner. However, whereas bSMase increased hepatocellular GSH levels, hSMase depleted GSH stores, an effect that was prevented by monensin and mannose 6-phosphate (M-6-P), suggesting that exogenous hSMase enters hepatocytes by endocytosis and is delivered to an endosomal/lysosomal acidic compartment. Interestingly, despite the differential effect of either SMases on cell GSH levels, both bSMase and hSMase increased γ-glutamylcysteine synthetase heavy-subunit chain (γ-GCS-HS) mRNA levels. Consistent with these findings on GSH regulation, hSMase, but not bSMase, generated reactive oxygen species (ROS), being accompanied by mitochondrial depolarization, suggesting that hSMase targeted mitochondria, leading to oxidative stress. Accordingly, hepatocytes displayed a selective sensitivity to hSMase in contrast to bSMase exposure, and depletion of GSH stores enhanced susceptibility to hSMase as a result of potentiation of ROS formation and caspase 3 activation. Thus, these findings reveal the ability of ASMase to induce oxidative stress as a result of the targeting of mitochondria, and that GSH depletion sensitizes hepatocytes to the ASMase-induced apoptosis.
355. Towards Cystic Fibrosis and Airway Gene Therapy: Evaluation of EGFP Gene Expression in Murine Nasal Airways Mediated by Simian Immunodeficiency Virus Vectors Pseudotyped with Sendai Virus Glycoproteins F and HN
Authors: Katsuyuki Mitomo, Makoto Inoue, Yasuji Ueda, Mie Ikegami, Uta Griesenbach, Eric W.F.W. Alton, Mamoru Hasegawa
Journal: Molecular Therapy (2005)

Cystic Fibrosis (CF) is the most common lethal autosomal recessive disease in the Caucasian, and the cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified to its causative gene. Mutations in the CFTR lead to imbalanced ion and water movement across the airway epithelium, resulting in thickened mucus, chronic bacterial infection and inflammation. Such severe pathological changes in airway are responsible for the morbidity and mortality in CF patients. Then, the airway epithelial cells are the important targets for CF gene therapy. However, few vectors can transduce them because of the existence of thickened mucus layer on the apical surface of epithelial cells and/or lack of virus receptors on apical site of the epithelial cells. We have shown that recombinant Sendai virus (SeV), murine parainfluenza virus, can easily penetrate the mucus layer and efficiently transduce the airway epithelial cells from the apical side. In order to improve the lentivirus vector entry, we developed a novel pseudotyped lentivirus vector based on a simian immunodeficiency virus (SIV: SIVagm TYO1) with SeV envelop proteins, fusion protein (F) and hemagglutinin-neuraminidase (HN). Although the SIV vector could not be pseudotyped with the intact F and HN, it could be successfully pseudotyped after the modification of cytoplasmic regions of both F and HN. Thus prepared F/HN pseudotyped SIV vector carrying EGFP transgene was produced by transient transfection in 293T cells to the titers up to 108 transduction units (TU)/ml, and easily concentrated to more than 1010 TU/ml by ultra-centrifugation with the same procedures for VSV-G pseudotyped vectors. Although the VSV-G pseudotyped lentivirus vectors have been used for administration to airways with pre-conditioning treatment using detergents, such treatment should be omitted considering the future clinical trials to human. From this point of view, F/HN pseudotyped SIV vector was evaluated in vivo in the absence of pre-conditioning. In this study, we administrated 100 |[mu]|l vector (4|[times]|108 TU/head) into mouse nasal cavity with syringe driver and observed EGFP expression. Although no or minimum expression was detected by administration of the VSV-G pseudotyped SIV vector, clear, frequent and stable GFP expression was observed in the epithelial cells of nasal cavity in the case of F/HN pseudotyped SIV vector even one month after the transduction. Detailed quantitative results will be summarized in the very near future. Our novel pseudotyped SIV vector with SeV envelope proteins, F and HN, would be of great value as a tool for gene therapy of respiratory diseases such as CF.
ULTRAFILTRATION OF THE VIRUS OF POLIOMYELITIS
Authors: Max Theiler, Johannes H. Bauer
Journal: The Journal of Experimental Medicine (1934)

From the ultrafiltration analysis the size of the virus of human poliomyelitis has been estimated to be somewhere between 12 and 17 mmicro. Technical difficulties encountered and the low concentration of the virus make it seem possible that the virus is even smaller.
GMC is given power to appeal judgments against doctors that it considers too lenient
Authors: C. Dyer
Journal: BMJ (2015)

Parliament has approved changes to the law to give the UK General Medical Council the right to appeal to the High Court if it considers that doctors have been treated too leniently by regulatory panels.1

The GMC has been pushing for this power since it hived off its adjudication function in fitness to practise cases to the operationally independent Medical Practitioners Tribunal Service in 2012, retaining only the investigation role.2

A new order made under section 60 of the Health Act 1999, just days before parliament is scheduled to be dissolved for the general election, gives the GMC the right of appeal and makes changes to plug gaps in its rules and speed up the …
Older Drivers and Physicians
Authors: Ricardo Martinez
Journal: JAMA (1995)

The article by Dr Levy and colleagues in this issue ofThe Journal<sup>1</sup>addresses the important issue of driver's license renewal for elderly individuals. Whether the reduction in crash mortality found by Levy et al is related to visual testing specifically or to a requirement for retesting in general, maximizing safety for older drivers is crucial as the number of drivers aged 70 years or older on the road increases from 13 million today to a projected 30 million by 2020.<sup>2</sup>Driving is an important mobility issue for older Americans, with 88% relying on private automobiles for most of their transportation needs.<sup>3</sup>A critical challenge is to balance public and individual safety with individual mobility needs. Older drivers are unfairly cast as a menace to other road users: older drivers account for the least number of miles driven, the least number of crashes, and the lowest crash
Sleep-related Breathing Disorder Is an Independent Risk Factor for Systemic Hypertension
Authors: LUDGER GROTE, THOMAS PLOCH, JÖRG HEITMANN, LENNART KNAACK, THOMAS PENZEL, JÖRG HERMANN PETER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The exact influence of sleep-related breathing disorder (SRBD) on blood pressure control remains unknown. We investigated the influence of different degrees of SRBD on daytime blood pressure and its association to documented hypertension by examining 1,190 consecutive patients referred for diagnosis of SRBD. The protocol includes clinical interview, physical examination, office blood pressure measurement, cholesterol, and blood gas analysis. Unattended home monitoring of nocturnal breathing was performed for assessment of SRBD activity (respiratory disturbance index [RDI]). RDI was independently and linearly associated with systolic blood pressure (unstandardized coefficient [B] = 0.07 ± 0.03, p = 0.03), diastolic blood pressure (B = 0.07 ± 0.02, p = 0 < 0.001), and heart rate (B = 0.10 ± 0.02, p < 0.001) at rest. The relative risk for hypertension (blood pressure ⩾ 160/95 mm Hg) increased with SRBD severity (odds ratio [OR], 4.15 for RDI ⩾ 40 versus < 5 [95% CI, 2.7 to 6.5]). This relative risk was also elevated in younger ( ⩽ 50 yr) compared with older patients ( > 50 yr) (OR, 7.15 versus 2.70 for RDI ⩾ 40 versus < 5). These cross-sectional clinical data suggest a relationship between SRBD severity and systolic blood pressure, diastolic blood pressure, and heart rate after control for confounders such as body mass index (BMI), age, alcohol/nicotine consumption, cholesterol level, and daytime Po 2 and Pco 2. SRBD is an independent risk factor for systemic hypertension with an increased likelihood in subjects ⩽ 50 yr of age. Grote L, Ploch T, Heitmann J, Knaack L, Penzel T, Peter JH. Sleep-related breathing disorder is an independent risk factor for systemic hypertension.
Essays In Medicine
Authors: Robert H. Moser
Journal: JAMA (1974)

With this issue The Journal is pleased to introduce a new feature: COMMENTARY. It will consist of essays written by acknowledged experts in a particular field of medical endeavor. Topics will range from those concerning hard science to those of philosophy, with side trails jutting off into ethics, sociology, religion, economics—at sites of junction with medical science.  Many of the essays will be solicited by the Editor; most, we hope, will arrive as spontaneous contributions, generated by anyone moved to comment on a subject of concern—who feels the need for more latitude in expression than that afforded in the more formal editorial.  Essay is defined as An analytic or interpretative literary composition usually dealing with a subject from a limited or personal point of view ( Webster's New Collegiate Dictionary , 1973). Lest this sound a trifle formidable, be it also known that The Journal is not averse to the light touch:
Progress in Defining the Causes of Idiopathic Dilated Cardiomyopathy
Authors: Virginia V. Michels
Journal: New England Journal of Medicine (1993)

Dilated cardiomyopathy can result from numerous underlying diseases, both intrinsic to the heart (such as coronary atherosclerosis) and extrinsic to the heart (such as catecholamine excess)1. However, there remain many patients with dilated cardiomyopathy of unknown cause. Medical and surgical treatments for this progressive disease are palliative, and the prognosis is generally poor. Indeed, idiopathic dilated cardiomyopathy is the primary indication for heart transplantation, at a cost of approximately $177 million annually2. Therefore, a better understanding of the causes and pathogenesis of the disease is urgently needed.It is likely that idiopathic dilated cardiomyopathy has multiple causes. Recently, . . .
An Unusual Case of Hypoprothrombinaemia Haemorrhagica
Authors: C. Gopalan, P. S. Venkatachalam
Journal: BMJ (1951)

Ainother interesting fact in this case is the rapidity of response after such a considerable period of aphasia, indicating that the cerebral structures involved were -functionally depressed and not destroyed.The imme- diate change in the psychiatric picture after the return of the speech function was especially striking and very instructive.
Predictors of Plasma DDT and DDE Concentrations among Women Exposed to Indoor Residual Spraying for Malaria Control in the South African Study of Women and Babies (SOWB)
Authors: Kristina W. Whitworth, Riana M.S. Bornman, Janet I. Archer, Mwenda O. Kudumu, Gregory S. Travlos, Ralph E. Wilson, Matthew P. Longnecker
Journal: Environmental Health Perspectives (2014)

Background: Few studies have examined predictors of DDT (dichlorodiphenyltrichloroethane) and DDE (dichlorodiphenyldichloroethylene) levels among residents in homes sprayed with DDT for malaria control with the aim of identifying exposure-reduction strategies.Methods: The present analysis included 381 women enrolled in the Study of Women and Babies (SOWB) during 2010–2011, from eight South African villages in the Limpopo Province, South Africa. Indoor residual spraying (IRS) occurred in half of the villages. Questionnaires regarding various demographic and medical factors were administered and blood samples were obtained. We classified the women into three exposure groups by type of residence: unsprayed village (n = 175), IRS village in household with a low likelihood of DDT use (non-DDT IRS household, n = 106), IRS village in household with a high likelihood of DDT use (DDT IRS household, n = 100). We used multivariable models of natural log-transformed DDT plasma levels (in micrograms per liter) and DDE (in micrograms per liter) to identify predictors for each group.Results: Median levels of DDT and DDE among women in unsprayed villages were 0.3 [interquartile range (IQR): 0.1–0.9] and 1.7 (IQR: 0.7–5.5), respectively. Median levels of DDT and DDE among women in DDT IRS households were 2.6 (IQR: 1.1–6.6) and 8.5 (IQR: 4.7–18.0), respectively. In unsprayed villages, women with water piped to the yard, rather than a public tap, had 73% lower DDT (95% CI: –83, –57%) and 61% lower DDE (95% CI: –74, –40%) levels. In DDT IRS households, women who reported taking more than six actions to prepare their home before IRS (e.g., covering water and food) had 40% lower DDT levels (95% CI: –63, –0.3%) than women who took fewer than four actions.Conclusion: The predictors of DDT and DDE plasma levels identified in the present study may inform interventions aimed at decreasing exposure. Among households where DDT is likely to be used for IRS, education regarding home preparations may provide an interventional target.Citation: Whitworth KW, Bornman RM, Archer JI, Kudumu MO, Travlos GS, Wilson RE, Longnecker MP. 2014. Predictors of plasma DDT and DDE concentrations among women exposed to indoor residual spraying for malaria control in the South African Study of Women and Babies (SOWB). Environ Health Perspect 122:545–552; http://dx.doi.org/10.1289/ehp.1307025
Isoniazid-Induced β-Hydroxybutyric Acidosis
Authors: Peter J. Piliero, Douglas G. Fish
Journal: Annals of Internal Medicine (2001)

Letters1 May 2001Isoniazid-Induced β-Hydroxybutyric AcidosisPeter J. Piliero, MD and Douglas G. Fish, MDPeter J. Piliero, MDAlbany Medical College; Albany, NY 12208 (Piliero, Fish)Search for more papers by this author and Douglas G. Fish, MDAlbany Medical College; Albany, NY 12208 (Piliero, Fish)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-9_Part_1-200105010-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest Miller and colleagues' report on lactic acidosis associated with stavudine (1). We report our recent experience with nucleoside-induced lactic acidosis complicated by isoniazid-induced β-hydroxybutyric (BHB) acidosis.In late 1999, HIV infection was diagnosed in a 29-year-old obese African-American woman after she presented with Pneumocystis carinii pneumonia. Her CD4 cell count at diagnosis was 0.025 × 109 cells/L, and her viral load was 100 000 RNA copies/mL. In early January 2000, she began receiving stavudine, lamivudine, and efavirenz. This regimen promptly suppressed viremia, with a concomitant increase in CD4 cell count. After reconstitution of ...References1. Miller KD, Cameron M, Wood LV, Dalakas MC, Kovacs JA. Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases. Ann Intern Med. 2000;133:192-6. [PMID: 0010906833] LinkGoogle Scholar2. Pahl MV, Vaziri ND, Ness R, Nathan R, Maksy M. Association of β hydroxybutyric acidosis with isoniazid intoxication. J Toxicol Clin Toxicol. 1984;22:167-76. [PMID: 0006094845] CrossrefMedlineGoogle Scholar3. Yarbrough BE, Wood JP. Isoniazid overdose treated with high-dose pyridoxine. Ann Emerg Med. 1983;12:303-5. [PMID: 0006625281] CrossrefMedlineGoogle Scholar4. Brinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet. 1999;354:1112-5. [PMID: 0010509516] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Albany Medical College; Albany, NY 12208 (Piliero, Fish) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoLactic Acidosis and Hepatic Steatosis Associated with Use of Stavudine: Report of Four Cases Kirk D. Miller , Miriam Cameron , Lauren V. Wood , Marinos C. Dalakas , and Joseph A. Kovacs Metrics Cited byIsoniazidAdverse reactions to first-line antituberculosis drugs 1 May 2001Volume 134, Issue 9_Part_1Page: 799KeywordsBicarbonatesHighly active antiretroviral therapyIsoniazidLactic acidosisNucleosidesProphylaxisPyridoxineViral loadViremiaVomiting ePublished: 1 May 2001 Issue Published: 1 May 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...