tbuckley/cabot-search huggingface dataset:
Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production.
Authors: A S Plump, S K Erickson, W Weng, J S Partin, J L Breslow, D L Williams
Journal: Journal of Clinical Investigation (1996)

In addition to its ability to remove cholesterol from cells, HDL also delivers cholesterol to cells through a poorly defined process in which cholesteryl esters are selectively transferred from HDL particles into the cell without the uptake and degradation of the lipoprotein particle. The HDL-cholesteryl ester selective uptake pathway is known to occur in human, rabbit, and rodent hepatocytes where it may contribute to the clearance of plasma cholesteryl ester. The selective uptake pathway has been studied most extensively in steroidogenic cells of rodents in which it accounts for 90% or more of the cholesterol destined for steroid production or cholesteryl ester accumulation. In this study we have used apo A-I-, apo A-II-, and apo E-deficient mice created by gene targeting in embryonic stem cells to test the importance of the three major HDL proteins in determining cholesteryl ester accumulation in steroidogenic cells of the adrenal gland, ovary, and testis. apo E and apo A-II deficiencies were found to have only modest effects on cholesteryl ester accumulation. In contrast, apo A-I deficiency caused an almost complete failure to accumulate cholesteryl ester in steroidogenic cells. These results suggest that apo A-I is essential for the selective uptake of HDL-cholesteryl esters. The lack of apo A-I has a major impact on adrenal gland physiology causing diminished basal corticosteroid production, a blunted steroidogenic response to stress, and increased expression of compensatory pathways to provide cholesterol substrate for steroid production.
A synthetic PPARγ ligand sensitizes breast cancer cells to tamoxifen-induced apoptosis.
Authors: Y Lee, J Kim, HJ Yun
Journal: Cancer Research (2009)

Abstract Abstract #1149 Blockade of estrogen receptor (ERa) by tamoxifen has been considered as a promising therapeutic approach to breast cancer. However, since not all the tumor cells are sensitive to tamoxifen, there is a need for the development of strategies to overcome the tamoxifen-resistance. Recently it has been known that ERa binds to peroxisome proliferator-activated receptor (PPAR) response element and negatively interferes with PPARg signaling in breast cancer cells, whose activation inhibits the growth of various cancer cells. Here we firstly wished to determine whether ERa inhibits PPARg-mediated cell death of human breast cancer cells. Troglitazone, a synthetic PPARg ligand, caused cell death and G1 arrest in both ERa-positive MCF-7 and ERa-negative MDA-MB-231 in a dose-dependent manner, but their degree shows differences between two cells. Troglitazone induced less cell death and G1 cell arrest in ERa-positive MCF-7 than ER-negative MDA-MB-231. The differences were abolished by PPARg knockdown using PPARg specific siRNA, indicating that ER inhibits PPARg-dependent anti-tumor action of PPARg agonist on breast cancer cells. Moreover, troglitazone sensitized breast cancer cells to tamoxifen-induced apoptosis, suggesting that the dose of tamoxifen for breast cancer therapy could be lowered by combination with troglitazone. Our results suggest that ERa-mediated inhibition of PPARg signaling pathways contribute to the growth of breast cancer cell and inhibition of ERa with PPARg activation could be a better approach for ERa-dependent breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1149.
Granulomatous Hypersensitivity After Use of Zirconium-Containing Poison Oak Lotions
Authors: William L. Epstein, James R. Allen
Journal: JAMA (1964)

OF THE METALS to which man is exposed, only zirconium and beryllium are known to induce delayed granulomatous hypersensitivity. Historically, axillary granulomas following the application of zirconium-containing stick deodorants<sup>1-4</sup>drew attention to this metal as a cause of allergic granulomas.<sup>5-8</sup>More recent cases have masqueraded as sarcoidosis.<sup>9-11</sup>In this report we describe another instance of presumed sarcoidosis due in fact to granulomatous hypersensitivity to zirconium in a topical remedy for poison oak dermatitis. <h3>Report of a Case</h3> A 16-year-old Japanese girl presented with a nonpruritic papular eruption of four months' duration on the face, forearms, and the dorsum of her hands. The lesions appeared as large, reddish-brown, flat-topped papules, 3 to 6 mm in diameter (Fig 1. Note: No topical therapy was used at this point.). She showed no signs of systemic illness. A biopsy revealed a "noncaseating dermal granuloma consistent with sarcoidosis." The clinical diagnosis was
Prisons and AIDS: A Public Health Challenge
Authors: B. Jaye Anno
Journal: JAMA (1997)

Prisons and AIDS I was excited about the opportunity to read<i>Prisons and AIDS</i>, particularly since there are so few books written on correctional health care. Ultimately, however, I was disappointed. The book contains very little new information. It relies heavily on the authors' prior published work, particularly that of Dr Hammett and his colleagues Rebecca Widom, Joel Epstein, Michael Gross, Santiago Sifre, and Tammy Enos. Beginning in 1988, Dr Hammett and others in his firm have conducted surveys of US prison systems and selected jails to determine seroprevalence rates of human immunodeficiency virus (HIV) in incarcerated populations under the auspices of the National Institute of Justice (NIJ). The most recent survey occurred in 1994, and the results were published in December 1995 by NIJ in<i>Issues and Practices, 1994 Update: HIV/AIDS in Correctional Facilities.</i> <i>Prisons and AIDS</i>uses much of the data and language of the prior book, either
RECENT IMMUNOLOGIC STUDIES IN HYPERSENSITIVITY TO TOBACCO
Authors: MARION B. SULZBERGER
Journal: JAMA (1934)

The studies which form the actual experimental basis of this report were carried out, principally, on patients with typical thrombo-angiitis obliterans and on a control group of smokers and nonsmokers without this disease.  Before entering into the discussion of my experimental results, I should like to mention certain fundamental immunologic concepts which led to the theory that thrombo-angiitis obliterans, a disease in which the role of tobacco has frequently been mentioned and acknowledged by most observers, might be a localized hypersensitivity of certain groups of blood vessels to circulating allergens derived from or contained in tobacco.  The first of these concepts is that of localized and circumscribed fixed specific hypersensitivity. Although examples of this may be found in every form of hypersensitivity and in every organ, they are best known, as is only natural, in the skin, and are most clearly evident to the immunologically minded dermatologist.  Perhaps the most
Malignancies, Prothrombotic Mutations, and the Risk of Venous Thrombosis
Authors: Jeanet W. Blom, Catharina Jacoba Maria Doggen, Susanne Osanto, Frits R. Rosendaal
Journal: JAMA (2005)

Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life.To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations.A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations.Risk of venous thrombosis.The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer.Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.
Overexpression of Heat Shock Protein 72 in Transgenic Mice Decreases Infarct Size In Vivo
Authors: Jonathan J. Hutter, Ruben Mestril, Eunice K.W. Tam, Richard E. Sievers, Wolfgang H. Dillmann, Christopher L. Wolfe
Journal: Circulation (1996)

Background Previous studies have demonstrated that induction of heat shock protein (HSP) 72 by whole-body hyperthermia reduces infarct size in an in vivo model of ischemia and reperfusion. Furthermore, hearts obtained from transgenic mice that overexpress HSP72 demonstrate improved functional recovery and decreased infarct size in vitro after global ischemia and reperfusion. Methods and Results To test the hypothesis that overexpression of HSP72 in transgenic mice reduces infarct size in vivo, transgenic mice that were heterozygous for a rat HSP70i gene ([+]HSP72) and transgene-negative littermate controls ([−]HSP72) were subjected to 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. Core body temperature was monitored with a rectal thermometer and maintained between 36.5°C and 37.0°C with a heating pad. Infarct size, determined by dual staining with triphenyltetrazolium chloride and phthalocyanine blue dye, was smaller in [+]HSP72 mice compared with [−]HSP72 mice (12.7±2.8% [n=7] versus 33.4±4.5% [n=6], infarct size/risk area, respectively; P &lt;.05; mean±SEM). Conclusions Overexpression of HSP72 reduces infarct size in this in vivo transgenic mouse model of myocardial ischemia and reperfusion.
Platelet-Derived 12-Hydroxyeicosatetraenoic Acid Plays an Important Role in Mediating Canine Coronary Thrombosis by Regulating Platelet Glycoprotein IIb/IIIa Activation
Authors: Atsushi Katoh, Hisao Ikeda, Toyoaki Murohara, Nobuya Haramaki, Hideki Ito, Tsutomu Imaizumi
Journal: Circulation (1998)

In the thrombotic process of acute coronary syndromes, the pathophysiological role of thromboxane A2 via cyclooxygenase is well established; however, the role of 12-HETE via 12-lipoxygenase is little known. Therefore, we used OPC-29030, a novel specific inhibitor of 12-HETE synthesis, to test whether platelet-derived 12-HETE is involved in mediating cyclic flow variations (CFVs) and platelet aggregation in stenosed and endothelium-injured canine coronary arteries.After developing CFVs, dogs received a vehicle or OPC-29030 intravenously. Plasma and intraplatelet 12-HETE levels increased after CFVs. OPC-29030 but not vehicle reduced CFVs, which was associated with decreases in plasma and intraplatelet 12-HETE levels. Cessation of OPC-29030 restored CFVs in association with increases in plasma and intraplatelet 12-HETE levels. ADP and U46619 induced ex vivo platelet 12-HETE production and aggregation. After OPC-29030 administration, the ADP- and U46619-induced increases in ex vivo platelet 12-HETE production and aggregation were inhibited significantly. Platelet aggregation was linearly correlated with platelet 12-HETE production. OPC-29030 suppressed activation of human platelet glycoprotein IIb/IIIa.OPC-29030 reduced intraplatelet 12-HETE levels, resulting in the inhibition of coronary thrombosis in vivo in dogs. OPC-29030 inhibited human platelet glycoprotein IIb/IIIa activation in vitro. Thus, platelet-derived 12-HETE may play an important role in mediating thrombotic process.
Points: British and American spelling of technical words
Authors: J. Haworth
Journal: BMJ (1985)

Mr P H Chapins and colleagues have provided information useful to practising physicians (25 May, p 1546).Although the authors viewed sigmoidoscopy as unhelpful in differentiating neoplastic (polyps, adenocarcinoma) from non-neoplastic sources (haemorrhoids, diverticula, etc), the data can be viewed as valuable in assessing the validity of rectal bleeding as a historical screening tool.Specifically, the simple characteristic of "no rectal bleeding" appears quite accurate in identifying those individuals without neoplastic disease.The 2 x 2 table is reconstructed from data in the article.The predictive value of a Relation between rectal bleeding and findings on siginoidoscopy Findings on sigmoidoscopy Carcinoma or No polyp or polyp >10cm carcinoma >10cm Rectal bleeding 4 44 No rectal bleeding 8 263positive finding, as described in the paper, is 4/48 or 8%-quite low.In contrast, the predictive value of a negative finding is 263/271 or 97%-that is, a history of no rectal bleeding accurately identified patients without neoplastic processes.While these results must be used cautiously when applied to a population different from that described in their study, it appears that a negative response to inquiry about rectal bleeding may be useful in identifying patients at low risk for rectosigmoid neoplasia.
A CONTRIBUTION TO THE QUESTION OF REMOVAL OF THE LENS IN MYOPIA.
Authors: HERBERT HARLAN
Journal: JAMA (1896)

My contribution is in the form of a report of two cases, both the result of accident, and in one case thirty-three years have passed between the accidental operation and the observation; much the longest period of which I am aware. Jno. Harvey, aged 32, a Welshman and laborer, by occupation, had always been very shortsighted. He carried in his pocket a pair of —13 D. glasses which he occasionally used for reading. By their help it was not necessary to hold the print so near his face. For distance, he said they were not much good. On January 8, he received a blow in the right eye, which, he said, had always been the better. Some hours later he came to me at the Presbyterian Eye and Ear Hospital. There was a bruise on the right cheek and eye lid and examination showed the lens still perfectly clear, dislocated
Haemophilia patients launch action against Bayer over contaminated blood products
Authors: D. Josefson
Journal: BMJ (2003)

A class action lawsuit has been launched against the Bayer and Baxter corporations on behalf of people with haemophilia in Asia and Latin America who contracted HIV or hepatitis through contaminated blood products supplied by the companies.

Also named in the lawsuit were the Armour Pharmaceutical Company and Alpha Therapeutic Corporation. The suit was filed in a US federal court in California.

All four companies are accused of distributing …
Longitudinal Banded Pigmentation of Nails Following Adrenalectomy for Cushing's Syndrome
Authors: Philip K. Bondy, Herbert J. Harwick
Journal: New England Journal of Medicine (1969)

INCREASED pigmentation of the skin and mucous membranes has been associated for many years with hypersecretion of corticotropin and melanocyte-stimulating hormone. Involvement of the integumentary appendages has attracted less attention. The two cases cited in this communication show that characteristic and striking alterations in pigmentation of nails may also occur when the melanocytes are stimulated very intensely.Case ReportCase 1. P.H. (Y-NHH 48–98–00), a 22-year-old white woman, was first seen at the Yale–New Haven Hospital in 1958 because of heartburn and irregular bowel habits. Examination revealed the typical physical features of Cushing's syndrome. Overproduction of cortisol was documented. Radiographs . . .
Synaptic Inhibition in the Olfactory Bulb Accelerates Odor Discrimination in Mice
Authors: Nixon M. Abraham, Veronica Egger, Derya R. Shimshek, Robert Renden, Izumi Fukunaga, Rolf Sprengel, Peter H. Seeburg, Matthias Klugmann, Troy W. Margrie, Andreas T. Schaefer, Thomas Kuner
Journal: Neuron (2010)
Conflicts of Interest in the Publication of Science
Authors: Drummond Rennie
Journal: JAMA (1991)

Allegations that greed and conflicts of interest are eroding the integrity of the scientific community<sup>1</sup>—a community funded with billions of federal dollars—have led the government to turn a vigilant eye toward the uses and potential abuses of scientific research. In response to such scrutiny, the US Public Health Service proposed guidelines to prevent conflicts of interest from interfering with federally funded research. The guidelines required all investigators involved in research funded by the National Institutes of Health—as well as their spouses and dependent children—to disclose "all financial interests and outside professional activities."<sup>2</sup>After facing "a firestorm of protest,"<sup>3</sup>the Public Health Service scrapped the guidelines, though it still hopes to develop new ones that do not disturb the research community so violently. This reaction was best expressed by Hittelman,<sup>4</sup>who criticized the "insidious assumption that seems to underlie the guidelines: that the university biomedical research
Molecular Mechanisms of RET Receptor–Mediated Oncogenesis in Multiple Endocrine Neoplasia 2B
Authors: Taranjit S. Gujral, Vinay K. Singh, Zongchao Jia, Lois M. Mulligan
Journal: Cancer Research (2006)

Abstract Multiple endocrine neoplasia 2B (MEN 2B) is an inherited syndrome of early onset endocrine tumors and developmental anomalies. The disease is caused primarily by a methionine to threonine substitution of residue 918 in the kinase domain of the RET receptor (2B-RET); however, the molecular mechanisms that lead to the disease phenotype are unclear. In this study, we show that the M918T mutation causes a 10-fold increase in ATP binding affinity and leads to a more stable receptor-ATP complex, relative to the wild-type receptor. Further, the M918T mutation alters local protein conformation, correlating with a partial loss of RET kinase autoinhibition. Finally, we show that 2B-RET can dimerize and become autophosphorylated in the absence of ligand stimulation. Our data suggest that multiple distinct but complementary molecular mechanisms underlie the MEN 2B phenotype and provide potential targets for effective therapeutics for this disease. (Cancer Res 2006; 66(22): 10741-9)
Pharmacologic eigenvalues: beating the rap on bone marrow failure
Authors: Stephen G. Emerson, Russell W. Garrett
Journal: Journal of Clinical Investigation (2010)

Patients suffering from sustained acute or chronic illness often have decreased white blood cell and platelet counts as well as anemia, and bone marrow studies routinely show only decreased numbers of blood precursor cells. While much has been recently learned about the cause of isolated anemia, the pathogenesis of true bone marrow failure (i.e., low bone marrow cellularity and low counts in multiple blood lineages) has remained elusive. In this issue of the JCI, Chen et al. present evidence that overactivation of mammalian target of rapamycin signaling in HSCs is found in two mouse models of bone marrow failure, and they show that treatment with rapamycin significantly normalizes the low blood counts.
Interferon-α therapy for hepatitis c virus infection after liver transplantation
Authors: Teresa L. Wright, Connie Combs, Michael Kim, Linda Ferrell, Peter Bacchetti, Nancy Ascher, John Roberts, Judith Wilber, Pat Sheridan, Mickey Urdea
Journal: Hepatology (1994)

The aims of this pilot study were to evaluate the safety and efficacy of interferon–α2b for treatment of hepatitis C virus infection in liver transplant recipients, to monitor changes in hepatitis C virus RNA levels with treatment and to determine pretreatment parameters predictive of a complete response. Eighteen patients with documented hepatitis C virus viremia and histological evidence of hepatitis after liver transplantation received 3 million units of α interferon three times weekly for at least 4 mo. Pretreatment serum aminotransferase levels were at least 1.5 times the upper limit of normal and no patient had concomitant hepatitis B virus infection. Response to therapy was defined as normalization of both aspartate and alanine aminotransferase at the end of treatment. Five patients (28%) had a complete response, whereas 13 (72%) had persistent elevation of one or both aminotransferases (nonresponders). At the end of therapy, hepatitis C virus RNA levels were reduced in both responders and nonresponders (p = 0.043 and 0.039, respectively by Wilcoxon signed rank test). After cessation of treatment, aminotransferases remained normal in four of five responders but serum hepatitis C virus RNA levels returned to pretreatment levels in responders and nonresponders. There was no significant change in histological score with therapy. Responders were more likely than nonresponders to have low pretreatment hepatitis C virus RNA levels and low serum bilirubin (p = 0.0004 and 0.0077, respectively). Responders tended to have a prolonged interval between transplantation and initiation of therapy (p = 0.10 by rank logistic regression analysis). Side effects resulted in early cessation of therapy in two patients and dose reduction in six. Histological evidence of possible rejection was seen in one patient. We conclude that normalization of liver enzymes can be seen in patients with posttransplant hepatitis C virus infection on interferon therapy and that treatment is associated with fall in hepatitis C virus RNA levels, regardless of biochemical response. However, virological changes are transient. Pretreatment variables such as hepatitis C virus RNA levels and serum bilirubin may aid in the selection of patients more likely to respond to therapy and the design of future controlled clinical trials. (Hepatology 1994;20:773-779).
Incidence of early post-operative iliofemoral thrombosis.
Authors: J P Bolton, V J Hoffman
Journal: BMJ (1975)

The doppler ultrasound probe was used to study 138 patients after major surgery to assess the incidence of iliofemoral thrombosis in the early postoperative period. The patients were simultaneously studied with the 125-I-fibrinogen uptake test. The accuracy of the ultrasonic technique was assessed concurrently by comparing its results with those of ascending phlebography in a separate group of patients. The ultrasound probe detected thrombus proximal to the calf but was inaccurate in locating its exact site. Of the 138 patients studied postoperatively 28 developed calf vein thrombosis detected istopically, but there was no evidence of iliofemoral thrombosis in any patient. Thus, spontaneous iliofemoral thrombosis in the early postoperative period is rare.