tbuckley/cabot-search huggingface dataset:
Abstract 2245: Overcoming cisplatin resistance by celastrol in cancer cells.
Authors: Zhi Shi
Journal: Cancer Research (2013)

Abstract Cisplatin is one of the most widely used cytotoxic anticancer drugs for the treatment of solid malignancies, including lung, testicular, ovarian, head and neck, colorectal, bladder cancers, etc. However, its clinical efficacy is often limited by the development of chemoresistance. Several mechanisms have been implicated in cisplatin resistance, such as reduced drug uptake, increased cellular thiol/folate levels and increased DNA repair. Celastrol, a quinone methide triterpene, is an active compenent of the traditional Chinese medicinal plant Tripterygium Wilfordii, which exhibits significant antitumor activity in different cancer models in vitro and in vivo. In this study, we sought to determine the effect of celastrol on cisplatin resistance cancer cells and the possible involved molecular mechanism. Our data show that celastrol had similar cytotoxic effects on both A549 parental and A549/DDP cisplatin resistant cells. The IC50 values of celastrol to both cell lines are at the concentration of μM range. Celastrol also induced cell apoptosis with ROS accumulation, loss of mitochondrial membrane potentials, cleavage of PARP and caspases in a dose- and time-dependent manner in both cell lines. These findings might provide significant strategy for overcoming cisplatin resistance in clinic, and define the novel mechanism of celastrol-induced anticancer activity. Citation Format: Zhi Shi. Overcoming cisplatin resistance by celastrol in cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2245. doi:10.1158/1538-7445.AM2013-2245 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
P5-07-04: Is a-L-Fucose Overexpressed on Cells of Aggressive Human Breast Cancers?
Authors: JJ Listinsky, GP Siegal, CM Listinsky
Journal: Cancer Research (2011)

Abstract Enzymatic removal of a-L-fucose (fucose) was shown over 20 years ago to abolish metastases in vivo in a rat model of mammary adenocarcinoma [J Cell Biochem 1988; 37: 49–59]. Since that time, evidence has accumulated to indicate that fucose is a functional effector in human breast cancer; essential for construction of the invasive and metastatic phenotypes. In light of these findings, the role of fucose in aggressive breast cancers is worthy of further investigation. Our group has modified the method of Wright et al. in order to selectively remove cell surface fucose from viable human breast cancer cells in vitro. In our experience, a 30 min incubation of breast cancer cells with α-L-fucosidase (3.2.1.51) leads to a loss of transformative abilities including decreased cancer cell adhesion to select extracellular matrix components, decreased invasion into complex extracellular matrices, decreased binding by relevant antibodies and lectins, and decreased adhesion of cells (rolling) to model endothelium under shear stress flow conditions. From this work we postulated that decisive differences in phenotypic and functional properties between treated and control human breast cancer cells should be obtainable with currently available models of aggressive disease. To that end, we and others have subsequently shown that human breast cancer cells express cell surface CD44 which carries fucosylated ligands and that its’ defucosylation altered its’ malignant phenotype.. Based on these precedents, it is reasonable to hypothesize that CD44-enriched breast cancer stem cell populations require fucose in order to exert their aggressive behavior. Assays to assess the role of fucose in these stem cells are apparent and include a battery of tests involving stem cell invasion into extracellular matrices, cell binding of antibodies or fucolectins, stem cell aggregation into spheroids, colony formation in soft agar, assessment of stem cell rolling/adhesion to endothelial cells or purified E-selectin under both static or physiological flow conditions and the ability to initiate tumors upon inoculation into animal models. We believe that new insights into aggressive breast cancer cell behaviors can be gained through the depletion of cell surface fucose from breast cancer cells. Knowledge gained from these studies should yield new insights when using current models of human breast cancer in vitro and in vivo. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-04.
Characterization of the Glomerular Antibody in Acute Poststreptococcal Glomerulonephritis
Authors: BERNARDO RODRÍGUEZ-ITURBE
Journal: Annals of Internal Medicine (1980)

Glomerular-fixed antibody was eluted from the kidney of a 17-year-old patient who died 2 weeks after the onset of acute poststreptococcal glomerulonephritis. Elevated titers of antibodies to streptococcal enzymes were found in the serum but not in the glomerular eluate. Streptococcal M protein and anti-M protein reactivity were not detected in the eluate. Immunoglobulin G was the only serum protein demonstrated in the eluate, and it was found to have anti-IgG activity highly concentrated with respect to the serum. These studies appear to indicate that anti-IgG is involved in the immune pathogenesis of acute poststreptococcal glomerulonephritis. Native IgG may be rendered autoimmunogenic by the streptococcus with subsequent antibody production to the neoautoimmunogen. Alernatively, anti-IgG may be produced to the IgG incorporated in an exogenous streptococcal antigen-antibody complex.
Global Fund freezes aid to Zambian health ministry
Authors: P. Wilson
Journal: BMJ (2010)

<h3>Objective</h3> To examine associations between measures of obesity in middle to early-old age with later-life MRI markers of brain aging. <h3>Methods</h3> We analyzed data from the Northern Manhattan MRI Sub-Study (n = 1,289). Our exposures of interest were body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and plasma adiponectin levels. Our outcomes of interest were total cerebral volume (TCV), cortical thickness, white matter hyperintensity volume (WMHV), and subclinical brain infarcts (SBI). Using multivariable linear and logistic regression models adjusted for sociodemographics, health behaviors, and vascular risk factors, we estimated β coefficients (or odds ratios) and 95% confidence intervals (CIs) and tested interactions with age, sex, and race/ethnicity. <h3>Results</h3> On average at baseline, participants were aged 64 years and had 10 years of education; 60% were women and 66% were Caribbean Hispanic. The mean (SD) time lag between baseline and MRI was 6 (3) years. Greater BMI and WC were significantly associated with thinner cortices (BMI β [95% CI] −0.089 [−0.153, −0.025], WC β [95% CI] −0.103 [−0.169, −0.037]) in fully adjusted models. Similarly, compared to those with BMI &lt;25, obese participants (BMI ≥30) exhibited smaller cortical thickness (β [95% CI] −0.207 [−0.374, −0.041]). These associations were particularly evident for those aged &lt;65 years. Similar but weaker associations were observed for TCV. Most associations with WMHV and SBI did not reach statistical significance. <h3>Conclusions</h3> Adiposity in early-old age is related to reduced global gray matter later in life in this diverse sample. Future studies are warranted to elucidate causal relationships and explore region-specific associations.
London after Tomlinson. Clinical research.
Authors: M. Green
Journal: BMJ (1992)

Sir Bernard Tomlinson's report focuses on London's health services, but his proposals have major implications for the future of clinical research--not just in London but in the United Kingdom as a whole. They must be seen in the context of a widely perceived decline in British research and development which also threatens clinical research. This article examines the implications of Tomlinson's proposals and related strategies and recommends the construction of a research market for the patient costs of clinical research to complement the NHS market for patient services introduced in 1991. These arrangements would help sustain the clinical research base and guarantee excellence.
Long-term Cardiovascular Safety, as Evaluated by Electrocardiographic Monitoring, of Budesonide/Formoterol Pressurized Metered-Dose Inhaler in African-American Patients With Moderate to Severe Asthma
Authors: R.W. Brown, C.D. O'Brien, U.J. Martin, T. Uryniak, K.L. Lampl
Journal: Journal of Allergy and Clinical Immunology (2012)
Parathion Residue Poisoning Among Orchard Workers
Authors: Thomas H. Milby, Fred Ottoboni, Howard W. Mitchell
Journal: JAMA (1964)

Following an outbreak of illness among peach harvesters, 186 peach orchard workers were studied in relation to pesticide application practices and fruit harvesting procedures representative of the orchards in which they worked. It was necessary first to establish a diagnosis of organic phosphate poisoning and then to associate observed illness with the intensity of parathion application. Information obtained revealed that, although parathion could easily be recovered from all elements of the orchard environment, it was not present in amounts sufficient to account for the observed illness. This inconsistency suggested the presence in the spray residue of a compound evolved from parathion alteration which was considerably more toxic than parathion, but identifiable by routine analytical procedures only as parathion. Paraoxon was considered a likely suspect and was postulated as a prime cause of the outbreak.
Vaccines for Children Program Off and Running
Authors: Charles Marwick
Journal: JAMA (1994)

DESPITE a stumble at the start, the Vaccines for Children Program, part of the nation's Childhood Immunization Initiative, is now well under way. "Vaccines have been ordered and shipped. No one should think that the program is not operating. No child in this country will be denied vaccination in a public clinic as a result of the lack of vaccine between now and January," promises Walter Orenstein, MD, who, as director of the National Immunization Program at the Centers for Disease Control and Prevention (CDC), Atlanta, Ga, is responsible for its implementation. Orenstein summarized the current status of the Childhood Immunization Initiative at a meeting of the National Vaccine Advisory Committee. Much of the rough ride that the vaccine purchasing effort has experienced was occasioned by the administration's move to set up an independent, centralized vaccine distribution system. The step soon came under strong industry and congressional criticism (<i>JAMA</i>. 1994;272:576-577),
Sawmill chemicals and carcinogenesis.
Authors: J Huff
Journal: Environmental Health Perspectives (2001)

Workers in wood industries are exposed to variable medleys of chemicals, both natural and synthetic. Additional exposures include fungi, bacteria, bark and wood dusts, solvents, paints, and various other wood coatings. These individual and conglomerate exposures have been associated with diverse occupational illnesses and hazards, including cancers. In this commentary, I summarize both experimental and epidemiologic carcinogenesis results for several chemicals used in the wood industry, as well as for wood dust. Working in the wood industries entails excess risks of cancers, among other diseases and workplace injuries. A key to preventing occupationally and environmentally associated cancers, as in the wood industries, is avoiding exposures to chemicals and wood dusts and, in particular, chemicals known to cause cancer in animals or/and humans.
THE OPERATIVE TREATMENT OF TUBERCULOSIS OF JOINTS—(EXCISION).Read in the Section on Surgery and Anatomy, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: ROBERT W. LOVETT
Journal: JAMA (1894)

The question of the operative treatment of joint disease should involve the discussion of several procedures; excision, arthrectomy, incision and ignipuncture. The limits of this paper, however, compel the writer to confine his attention to the consideration of the place of excision in the treatment of tuberculous joint disease. On this subject there is a wide range of opinion in the surgical world. Some surgeons advocate early excision as a routine treatment in tuberculous joint disease; others would never excise at all, because they consider the operation as rarely necessary, and as dangerous; and a third faction believes that excision is to be kept in the background until conservative measures (<i>i. e.</i>, mechanical treatment) have had a faithful trial. Mechanical treatment is a term which has been often applied to the loosest and most incomplete imitations of proper conservative measures. Consequently, when one attempts to define the sphere of operative
Oxalosis and the E-Ferol Toxicity Syndrome
Authors: Robert A. J. Conyers
Journal: JAMA (1986)

To the Editor.—  There is a sense of deja vu about the description by Bove et al 1 of the adverse reactions and deaths that followed the intravenous administration of the vitamin E preparation E-Ferol to low-birth-weight infants. The syndrome of renal dysfunction, hepatic dysfunction, metabolic acidosis, and tissue oxalosis has many similarities to that which occurs in patients who received parenterally large amounts of xylitol. 2 When first observed, the xylitol toxicity syndrome was unexpected, and, indeed, it was concluded that the oxalosis was not causally related to the infusion of xylitol. 2 However, both animal and biochemical studies have since confirmed that oxalate or oxalate precursors can be formed during the hepatic metabolism of xylitol, 2 with the enzymes fructokinase and aldolase playing important roles in the metabolic production of the oxalate precursor glycolaldehyde from xylitol. 2,3 In terms of a one-compartment model for the renal elimination of
Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes
Authors: G C Viberti, R W Bilous, D Mackintosh, J J Bending, H Keen
Journal: BMJ (1983)

The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy. After a planned run in observation period of 10 to 24 months patients entered a programme of continuous subcutaneous insulin infusion for up to 24 months. Glycaemic control was promptly and significantly improved and optimal glycaemic values sustained throughout the study. Blood pressure was maintained stable. A control group of six nephropathic diabetics was studied receiving conventional insulin injection treatment but also with blood pressure control over the same period. Despite greatly improved metabolic control in the infusion treated group no significant change in the rate of decline of glomerular filtration rate could be shown, the plasma creatinine concentrations continued to increase, and the fractional clearance of albumin and IgG rose progressively, indicating progression of glomerular damage. The conventionally treated control group behaved similarly. In a single patient receiving the continuous infusion the rate of decline of the glomerular filtration rate slowed considerably, suggesting that the response to strict diabetic control may differ in some patients. These findings suggest that by the time glomerular function has started to fail in diabetic nephropathy the process culminating in end stage renal failure has become self perpetuating and is little influenced by the degree of metabolic control. A new definition of potential clinical diabetic nephropathy is proposed that will permit identification of patients at risk and earlier intervention by glycaemic correction in an attempt to arrest diabetic renal disease.
SOME SPECIAL FEATURES OF MASSACHUSETTS' PROGRAM FOR VENEREAL DISEASE CONTROL
Authors: EUGENE R. KELLEY
Journal: JAMA (1924)

In recent years, venereal disease control programs have been presented and discussed from various angles at all kinds of medical meetings. After the high tide of enthusiasm in this direction, engendered by the abnormal conditions of the war time period, most health administrators expected that there would be a recession of financial and popular interest in this newly inaugurated work of health departments. This has occurred; also many tentative schemes enthusiastically advocated during the hectic war time period, particularly in the direction of popular education and forcible repression, have failed to meet the acid test of consistent support by general public sentiment. Appropriations have in many instances fallen off sharply, and in some instances practically disappeared. It has been demonstrated that it is not at present possible to get the public to receive educational, epidemiologic or isolation policies for syphilis or gonorrhea on the same plane and in the same
New FDA Web Sites
Authors: Bernard A. Schwetz
Journal: JAMA (2001)

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Assessment of the long-term safety and effectiveness of etanercept for the treatment of psoriasis in an adult population
Authors: Kim A. Papp, Yves Poulin, Robert Bissonnette, Marc Bourcier, Darryl Toth, Leslie Rosoph, Melanie Poulin-Costello, Mike Setterfield, Jerry Syrotuik
Journal: Journal of the American Academy of Dermatology (2010)
Diagnosing Ventilator-Associated Pneumonia
Authors: Antoni Torres, Santiago Ewig
Journal: New England Journal of Medicine (2004)

The establishment of an appropriate diagnosis of ventilator-associated pneumonia is one of the most crucial and difficult issues in the care of critically ill patients. Established clinical criteria alone, such as new or progressive infiltrates on chest radiography, together with fever, leukocytosis or leukopenia, and purulent tracheobronchial secretions, have been shown to be of limited diagnostic value. When the findings on histologic analysis and cultures of lung samples obtained immediately after death were used as references, the presence of chest infiltrates plus two of the three criteria mentioned above had a sensitivity of 69 percent and a specificity of 75 . . .
Sex differences in mathematical abllity: Genes, environment, and evolution
Authors: Jeffrey W. Gillger
Journal: Behavioral and Brain Sciences (1996)

Abstract Geary proposes a sociobiological hypothesis of how (and why) sex differences in math and spatial skills might have jointly arisen. His distinction between primary and secondary math skills is noteworthy, and in some ways analogous to the closed versus open systems postulated to exist for language. In this commentary issues concerning how genes might affect complex cognitive skills, the interpretation of heritability estimates, and prior research abilites are discussed.
Human Papillomavirus Type 16 Periungual Carcinoma-Reply
Authors: Gerard J. Nuovo
Journal: JAMA (1989)

In Reply.—  The letter by Drs Gordon and Palusci expresses concern about finding HPV 16 in a nongenital site. They ask whether HPV 16 in condylomata acuminata could be transferred by nonsexual transmission. Human papillomavirus 16 is rarely associated with condylomata acuminata. We have analyzed more than 100 such lesions of the vulva and penis and have never found HPV 16; HPVs 6 and 11 are found in more than 90% of these lesions. 1 We do not believe that the detection of HPV 16 in finger carcinomas per se has any direct implications in the reporting, diagnosis, or investigation of child sexual abuse. Human papillomaviruses 6 and 11 are the most common types in genital condylomata in children. 2,3 Further, it is possible that the HPV 16 in these finger lesions (all in adults) was transmitted by sexual means. Our observation that HPV 16 is not associated with skin
Prevention of Psychopathology with Early Interventions
Authors: George N. Christodoulou
Journal: Psychotherapy and Psychosomatics (1991)

Early interventions aiming at prevention from future psychopathology are critically evaluated. These interventions include: genetic psychiatric counselling, family planning, improvement of the physical health of the population, prenatal care, intervention in childhood, improvement of the physical health of the child, improvement of the home environment and improvement of the school environment. Although concrete evidence about the effectiveness of many of the above methods is lacking, they are nevertheless worth applying because on an individual basis they often contribute to the alleviation of human suffering. It is pointed out that early preventive interventions are particularly indicated in predisposed individuals (e.g. persons with hereditary predisposition for schizophrenia who must be protected from perinatal complications in order to be prevented from future development of this illness) or high-risk groups (e.g. the siblings of 'battered' children who have a greater probability of being abused by their parents, or 'battered' children who, when becoming parents, have a raised probability of abusing their own children).
Lack of prognostic value of the periodic acid‐schiff reaction and blast cell size in childhood acute lymphocytic leukemia
Authors: Michael T. Shaw, G. Bennett Humphrey, Roberta Lawrence, Diana B. Fischer
Journal: American Journal of Hematology (1977)

Abstract Conflicting evidence has been published as to the prognostic significance of the periodic acid‐Schiff (PAS) reaction and cell size in acute lymphocytic leukemia (ALL). Therefore, a large collaborative study was undertaken to evaluate the prognostic significance of the PAS reaction and cell size of bone marrow lymphoblasts obtained at the time of diagnosis in children with ALL. Known prognostic factors (age and white blood cell [WBC] counts) were also evaluated. Data from 80 newly diagnosed cases of ALL were analyzed. These patients were treated with similar therapy by members of the Pediatric Division of the Southwest Oncology Group. The PAS reaction was scored. Microlymphoblasts were defined as having a diameter of ≤ 12 μm; macrolymphoblasts, &gt; 12 μm. Patients 10 years and older at the time of diagnosis had a significantly shorter duration of first remission and survival than those younger than 10 years. Those with pretreatment peripheral WBCs of ≤ 25,000/μl had significantly longer duration of first remission and survival than those with a peripheral WBC &gt; 25,000/μl. There was no significant difference in duration of first remission or survival in patients having predominantly macrolymphoblastic or microlymphoblastic marrows. PAS reaction was of no value in predicting the duration of first remission or survival.