tbuckley/cabot-search huggingface dataset:
Molecular epidemiology of aflatoxin exposures: validation of aflatoxin-N7-guanine levels in urine as a biomarker in experimental rat models and humans.
Authors: J D Groopman, C P Wild, J Hasler, C Junshi, G N Wogan, T W Kensler
Journal: Environmental Health Perspectives (1993)

Human epidemiology and experimental animal data have provided the statistical association and biological information necessary to propose that aflatoxins are risk factors for human liver cancer. As liver cancer causes at least 200,000 deaths per year, prevention measures must be developed to ameliorate this nearly always fatal disease. Preventive strategies will be facilitated by the identification of individuals at high risk. It is the goal of the molecular dosimetry field to provide facile and accurate biomarkers to identify people at high risk for carcinogen exposure and consequent adverse health effects. We have developed methods to defect the major aflatoxin DNA adduct, aflatoxin N7-guanine (AFB-N7-guanine), in urine, examined the dose-response characteristics in people living in China and The Gambia, and have found an excellent association of this biomarker with exposure. In addition to exposure studies in people, our laboratories have monitored AFB-N7-guanine excretion in the urine of rats whose risk for developing cancer has been modulated with dietary chemoprotective agents such that independent groups of animals receiving the same dosage of aflatoxin B1 were at either high or low risk for tumorigenesis. The production of DNA damage by aflatoxins is not the exclusive mechanism for liver cancer. Many other factors, including hepatitis B virus, cell proliferation, and nutritional status, can exert strong modification effects in human disease. Thus, molecular epidemiological investigations that examine only one biomarker may greatly underestimate or overestimate the risk for an individual.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 2108: New analogues of benzyl-isothiourea showed Rb-Raf disruption and anti-cancer activity
Authors: Monika Verma, Jackie Johnson, Michelle Kovacs, Sandeep Singh, Xin Wu, Nicholas Lawrence, Said Sebti, Srikumar Chellappan
Journal: Cancer Research (2011)

Abstract The retinoblastoma tumor suppressor protein Rb, is a vital regulator of the mammalian cell cycle which is inactivated by phosphorylation. We had shown that Raf-1 kinase binds and phosphorylates Rb early in the G1 phase facilitating its subsequent phosphorylation by cyclin dependent kinases. This phosphorlation released transcriptionally active E2Fs from Rb to facilitate S-phase entry. Disruption of Rb-Raf protein-protein interaction could prevent proliferation and angiogenesis, leading to inhibition of tumor growth in mouse models. We had earlier identified an orally active small molecule, Rb/Raf-1 disruptor 251 (RRD-251) that potently and selectively disrupts Rb/Raf-1 but not Rb/E2F, Rb/prohibitin, Rb/cyclin E or Rb/HDAC interactions. Here, we have made efforts to analyze additional analogues of RRD251; we focused on XW-19B and XW-35B. These compounds inhibited Rb-Raf interaction in vitro and in vivo as shown by ELISA and Immunoprecipitation-Western blot analysis. They also inhibited cell viability, proliferation, migration, invasion, angiogenesis and adherence-independent growth of human lung cancer cell lines A549. XW-19B inhibited tumor growth significantly in human A549 xenograft model in nude mice, compared to control while XW-35B showed certain amount of toxicity to animals at 50MPK. Overall, these results showed that Rb-Raf disruptors XW-19B and XW-35B have potential anticancer activity. Thus, selective targeting of Rb/Raf-1 interaction seems to be a promising approach for developing novel chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2108. doi:10.1158/1538-7445.AM2011-2108
Bronchodilator Effect of Oral Salbutamol in Asthmatics Treated with Corticosteroids
Authors: S. S. Parker, Y. F. J. Choo-Kang, E. J. Cooper, S. J. Cameron, I. W. B. Grant
Journal: BMJ (1971)

In a double-blind trial the effect on ventilatory function of oral salbutamol (in two different doses) and a placebo were studied in 12 patients with chronic asthma receiving regular maintenance treatment with prednisolone. Salbutamol in a dose of 4 mg four times daily, given for a period of four weeks, produced a sustained and statistically significant increase in peak expiratory flow rate over the pretreatment recordings. This effect was not observed with a lower dose of salbutamol (2 mg four times daily) or with a placebo. Salbutamol in the higher dose would seem to be an effective and safe oral bronchodilator that can be recommended for the treatment of mild or moderate asthma. The duration of treatment in this study was, however, limited to four weeks, and it is not known whether effective bronchodilatation would be maintained if the drug were given for longer periods.
Your Name Escapes Me
Authors: Conrad Rosenberg
Journal: Annals of Internal Medicine (1992)

Ad Libitum1 October 1992Your Name Escapes MeConrad Rosenberg, MDConrad Rosenberg, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-7-615_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptLike polished pebbles worn smooth, aging neurones no longer sift and store memories but flow them past unhindered as through a sluice leaving murky puddles as residue.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, NY 10044 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1992Volume 117, Issue 7Page: 615-615KeywordsAgingMemory ePublished: 1 December 2008 Issue Published: 1 October 1992 PDF downloadLoading ...
Indian patients go to court over cancer drug
Authors: Ganapati Murdur
Journal: BMJ (2004)

India's Supreme Court has admitted a petition from an organisation representing cancer patients that challenges the government's decision to grant Novartis the exclusive marketing rights for imatinib, a drug that has emerged as a frontline treatment for chronic myeloid leukaemia.

The petitioner, the Cancer Patients Aid Association, has said that exclusive marketing rights for the drug would eliminate cheaper generic versions of the drug and make the treatment unaffordable to thousands of patients in India.

“Shutting down access to the drug by making it unaffordable is tantamount to denying patients the right to life,” said Mr Yogendra Sapru, …
Anthrax Toxin Induces Macrophage Death by p38 MAPK Inhibition but Leads to Inflammasome Activation via ATP Leakage
Authors: Syed Raza Ali, Anjuli M. Timmer, Sameera Bilgrami, Eek Joong Park, Lars Eckmann, Victor Nizet, Michael Karin
Journal: Immunity (2011)
Perihepatitis and Salpingitis
Authors: Sylvain Fribourg
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Drs Litt and Cohen in their recent report have based their diagnosis of salpingitis on "the triad of lower abdominal pain, bilateral pelvic adnexal tenderness, and tenderness on motion of the uterine cervix." The diagnosis of perihepatitis "was confirmed in one patient and made in another patient who underwent laparoscopy." In all the other patients in the report, the diagnosis of perihepatitis was only presumptive and not so confirmed. Jacobson and Weström,<sup>1</sup>using many more criterions than the aforementioned triad to make a provisional diagnosis of salpingitis, found at laparoscopic examination of 905 such patients that 35% did not have salpingitis, 23% had no pathological changes, and 12% had other disease. Salpingitis was confirmed in 65% of the cases reviewed. This report has served me well by casting doubt in my mind when I am certain, on the basis of whatever clinical criterions I wish to
Distinct roles for B7-1 (CD-80) and B7-2 (CD-86) in the initiation of experimental allergic encephalomyelitis.
Authors: M K Racke, D E Scott, L Quigley, G S Gray, R Abe, C H June, P J Perrin
Journal: Journal of Clinical Investigation (1995)

The activation and differentiation of T cells require both antigen/MHC recognition and costimulatory signals. The present studies examined the role of B7-1 (CD80) and B7-2 (CD86) costimulation in the prototypic autoimmune disorder, experimental allergic encephalomyelitis (EAE). In adoptively transferred EAE, in vitro activation of myelin basic protein (MBP)-specific lymph node cells was inhibited by the combination of anti-CD80 plus anti-CD86, but not individually. However, in actively induced disease, one injection of anti-CD80 significantly reduced disease, while anti-CD86 exacerbated disease. Interestingly, one injection of CTLA-4Ig suppressed disease, while multiple injections resulted in enhanced disease. Thus, the costimulation provided by B7-1 molecules appears to be important for the development of encephalitogenic T cells. The enhanced disease caused by multiple injections of CTLA-4Ig or a single injection of anti-CD86 suggests an inhibitory function for CD86 interaction with its counterreceptors CD28 and CTLA-4 in EAE. Alternatively, these results are consistent with an essential timing requirement for the coordinated interaction of B7 and CD28 family receptors, and that disruption of this critical timing can have opposing results on the outcome of an immune response.
Judge orders South African health minister to do her job properly and bans unauthorised trials
Authors: Pat Sidley
Journal: BMJ (2008)

South African doctors belonging to the South African Medical Association and the AIDS activist group the Treatment Action Campaign have won a victory against the country’s health minister, Manto Tshabalala-Msimang, several top government employees, and Matthias Rath, who manufactures and sells vitamins as a treatment for AIDS.

The Cape High Court has effectively stopped Dr Rath from selling his supplements or conducting clinical trials that are not authorised by the Medicines Control Council (MCC). At the same time it has ordered the health minister to do her job properly in ensuring that treatments requiring registration are properly scrutinised.

The medical association and …
A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease
Authors: Margaret L. MacMillan, Daniel Couriel, Daniel J. Weisdorf, Gisela Schwab, Nancy Havrilla, Thomas R. Fleming, Saling Huang, Lorin Roskos, Shimon Slavin, Richard K. Shadduck, John DiPersio, Mary Territo, Steve Pavletic, Charles Linker, Helen E. Heslop, H. Joachim Deeg, Bruce R. Blazar
Journal: Blood (2006)
Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover
Authors: P R Gibson, I Birchall, O Rosella, V Albert, C F Finch, D H Barkla, G P Young
Journal: Gut (1998)

Background —The functions of urokinase in intestinal epithelia are unknown. Aims —To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. Methods —Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. Results —From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt ( r =0.68; p&lt;0.005) and per 100 crypt cells ( r =0.75; p&lt;0.001), but not with crypt column height. Conclusions —Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine.
Stimulation of Prostacyclin Synthesis by Physical Exercise in Type I Diabetes
Authors: Veikko A Koivisto, Marja Jantunen, Timo Sane, Eero Helve, Risto Pelkonen, Lasse Viinikka, Olavi Ylikorkala
Journal: Diabetes Care (1989)

We examined the effect of short- and long-term exercise on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TXA2) synthesis in type I (insulin-dependent) diabetic patients and healthy control subjects. PGI2 synthesis was assessed by determining the urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha and TX synthesis by measuring TXB2 in serum and urine. In the resting state, prostanoid excretion and concentrations were similar in diabetic and control subjects. During 40 min of ergometric cycling exercise, the urinary excretion of 6-keto-PGF1 alpha (a hydration product of vasodilatory PGI2) increased 5.8-fold more in the 12 control subjects than in the 15 diabetic patients (P less than .02). Serum TXB2 concentration rose similarly in diabetic patients and control subjects (P less than .05). During a 75-km competitive cross-country ski race (7 h, 30 min), urinary excretion of 6-keto-PGF1 alpha rose 1.9-fold in 7 diabetic (P less than .05) and 3.3-fold in 10 control (P less than .001) subjects, whereas urinary dinor excretion, reflecting vascular PGI2 synthesis more closely, increased only in the control subjects (P less than .01). Urinary TXB2 excretion remained unchanged in both groups during long-term exercise. These data suggest that diabetic patients have normal PGI2 and TXA2 synthesis in the resting state but diminished PGI2 response to both acute and prolonged exercise.
Ticlopidine‐induced aplastic anemia: Two new case reports, review, and meta‐analysis of 55 additional cases
Authors: A. Symeonidis, A. Kouraklis‐Symeonidis, U. Seimeni, A. Galani, N. Giannakoulas, E. Fragopanagou, M. Tiniakou, P. Matsouka, N. Zoumbos
Journal: American Journal of Hematology (2002)

Abstract Ticlopidine‐induced aplastic anemia (TIAA) is considered very uncommon. We present two new cases, and we review 55 additional cases from the literature. The first case concerns a 70‐year‐old man who developed severe aplastic anemia 7 weeks after treatment with 500 mg of ticlopidine daily. The patient sustained a severe septic episode, was treated with antibiotics and GM‐CSF, and recovered the 14 th day after ticlopidine withdrawal. The second was an 82‐year‐old man receiving ticlopidine for 2 years when, during a febrile episode, he was found neutropenic with marrow aplasia. Ticlopidine withdrawal and treatment with antibiotics, transfusions, and G‐CSF helped him to recover. When the data of the 57 patients are evaluated, a reversible direct cytotoxic effect of ticlopidine on the pluripotent/bipotent hematopoietic progenitor stem cell is proposed. It is estimated that the real incidence if TIAA is higher, and many cases, initially presented as agranulocytosis ± thrombocytopenia, might be true aplastic anemias, not proven by marrow aspiration or trephine biopsy. There is no effective monitoring to prevent this side effect. Recombinant growth factors appear not to help in shortening the neutropenic period. Am. J. Hematol. 71:24–32, 2002. © 2002 Wiley‐Liss, Inc.
Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier
Authors: Jens-Michael Jensen, Stefan Schütze, Michael Förl, Martin Krönke, Ehrhardt Proksch
Journal: Journal of Clinical Investigation (1999)

Epidermal TNF expression increases in response to cutaneous permeability barrier disruption and wound healing. TNF signaling is mediated by acid and neutral sphingomyelinases (A- and N-SMase), which generate ceramide, an important regulator of proliferation, differentiation, and apoptosis. In the epidermis, ceramide is known to be an integral part of the extracellular stratum corneum (SC) lipid bilayers that constitute the permeability barrier of the skin. We show here that topical application of TNF after experimental injury to the SC of hairless mice (hr–/–) enhances barrier repair. In TNF receptor p55–deficient (TNF-R55–deficient) mice (hr+/+), cutaneous barrier repair was delayed compared with wild-type (hr+/+) or TNF-R75–deficient (hr+/+) animals. After barrier disruption in hairless (hr–/–) and wild-type (hr+/+), but not in TNF-R55–deficient (hr+/+) mice, the enzymatic activities of both A-SMase and N-SMase were significantly enhanced. Stimulation of SMase activities was accompanied by an increase in C24-ceramide levels. Most A-SMase activity in hairless mice (hr–/–) was found in the outer epidermal cell layers and colocalized in the lamellar bodies with A-SMase and sphingomyelin. Reduction of epidermal A-SMase activity by the inhibitor imipramine resulted in delayed permeability barrier repair after SC injury. Together, these results suggest that TNF-R55 signaling pathways contribute to cutaneous permeability barrier repair through SMase-mediated generation of ceramide.
Renal response to a saline load in well-compensated alcoholic cirrhosis
Authors: Florence Wong, Denise Massie, Paul Hsu, Francis Dudley
Journal: Hepatology (1994)

A total of 29 patients with well–compensated alcoholic cirrhosis and 9 healthy control subjects of similar age and sex were studied to assess their response to a challenge of 2 L of normal saline infused over a 1 hr period. Patients with cirrhosis had an adequate effective arterial blood volume in the basal state as assessed by neurohumoral markers of vascular filling. They also had a lower renal vascular resistance (p = 0.048) and a higher glomerular filtration rate (p = 0.014) than the controls, indicating the presence of renal vasodilation. Both groups were in sodium balance, but the patients with cirrhosis had a higher filtered load of sodium, an increased proximal tubular reabsorption of sodium (p = 0.015) and a decreased fractional excretion of sodium (p &lt; 0.001). The administration of a saline load was not accompanied by any significant changes in the renal circulation in the patients with cirrhosis. They were unable to suppress their proximal tubular reabsorption of sodium to the same extent as the controls (p = 0.012), so by the fourth hour a significant difference in the rate of urinary excretion of sodium was evident. In the patients with cirrhosis, glomerular filtration rate before and after the saline load correlated significantly with indocyanine green extraction (r = 0.65; p = 0.002), whereas the tubular handling of sodium was dependent on antipyrine clearance (r = 0.80; p &lt; 0.001). The results indicate that in well–compensated alcoholic cirrhosis, abnormalities in the renal circulation and tubular handling of sodium occur before evidence exists of a decreased effective arterial blood volume and are independent, with the renal vasodilatation being related to the extent of intrahepatic shunting, whereas impaired renal tubular sodium handling is dependent on hepatic function. These results are consistent with the hypothesis that, in cirrhosis, activation of neurohumoral pressor systems is not solely responsible for the changes in sodium homeostasis that predispose to the development of ascites. (Hepatology 1994;20:873-881).
Adenomatous Polyps of the Colon
Authors: Joel S. Levine, Dennis J. Ahnen
Journal: New England Journal of Medicine (2006)

A 52-year-old man with no personal or family history of colon cancer, colonic polyps, or inflammatory bowel disease underwent a screening colonoscopy that showed no abnormalities except for a 1.5-cm pedunculated polyp at the hepatic flexure that was removed by means of a snare with cautery. The polyp was a tubulovillous adenoma without high-grade dysplasia. How should his care be managed?
The Soda Crush-Reply
Authors: Michael Q. Cosio
Journal: JAMA (1989)

<h3>In Reply.—</h3> Dr Payne's suggestion for a warning label is a practical one. Such a stick-on label is available from Vendo of California, free. However, the label is too small, measuring 6.4×8.3 cm (21/2 × 3 1/4 in). It is removable and it is not issued with the machine. To be effective, such a label should be large, nonremovable, part of the manufactured machine, and displayed prominently on the front of the machine at eye level. I believe that these machines are intrinsically unstable and that redesigning is necessary. They are top-heavy, standing on a narrow base. Hence, they tip over at very small angles of inclination. When interviewed, the patients stated that it was easy to tip the machines, despite their intimidating size and weight. Additional engineering analysis has revealed that even smaller forces applied correctly can tip the machine. It is possible to rock the machine, using the
Contact allergies in haemodialysis patients: a prospective study of 75 patients
Authors: C. Gaudy‐Marqueste, C. Jouhet, M. Castelain, P. Brunet, Y. Berland, J. J. Grob, M. A. Richard
Journal: Allergy (2009)

Haemodialysis exposes patients to many potentially sensitizing allergens.The primary objective of this study was to evaluate the prevalence of delayed hypersensitivity in a population of haemodialysis patients. Secondary objectives were to identify the possible risk factors for contact sensitization and to propose a series of skin tests adapted to haemodialysis patients.A prospective monocentric study was carried out in a nonselected population of haemodialysis patients. For each patient, medical history of atopy and allergic contact dermatitis, ongoing treatments (including topical ones), presence of eczema at the site of vascular access for haemodialysis were recorded. Allergological investigation included delayed hypersensitivity tests (European Environmental and Contact Dermatitis Research Group battery, tests GERDA, additional list and a battery of antiseptics and other dialysis-specific allergens) and latex skin prick test.Seventy-five patients (41 men, 34 women, mean age of 65 years old), with a mean 3.8 years under dialysis, were included. Nineteen patients (25%) had at least one positive skin test and 13 (17%) a positive patch test to at least one allergen relative to dialysis process including eight tests to lidocaine-prilocaine cream and three to povidone-iodine. Tests results seemed clinically relevant since nine patients had localized pruritus at the fistula site and six patients active eczema around it.Contact sensitizations are frequent in haemodialysis patients and are linked to vascular access conditioning especially the use of lidocaine-prilocaine cream. Designing a specific test battery could help to diagnose the potential allergens and subsequently to give advice to avoid contact with sensitizing agents.