tbuckley/cabot-search huggingface dataset:
Abstract 2142: Signaling pathways involved in apoptosis-resistance against doxorubicin analogues in murine mammary cells; Role of protein kinase C delta (PKCΔ)
Authors: María Inés Díaz Bessone, Damian E. Berardi, Paola B. Campodónico, Leonard Lothstein, Laura B. Todaro, Elisa D. Bal de Kier Joffé, Alejandro J. Urtreger
Journal: Cancer Research (2011)

Abstract In this work we have analyzed whether the overexpression of PKCΔ in murine mammary cells (NMuMG) is able to alter cell death susceptibility to two chemotherapeutic drugs derived from doxorubicin (AD198 and AD288), and evaluate the signaling pathways involved in this process. Similarly to doxorubicin, the mechanism of action of AD288 involves the generation of DNA damage whereas, it has been proposed that AD198 induces apoptosis by activating PKC isoforms, in particular PKCΔ. By western blot we could determine that NMuMG-PKCΔ cells showed an increase in the activation and/or expression of different molecules and signaling pathways involved in cell survival such as Bcl-2, pBad, PI3K/Akt y NFκB. Therefore PKCΔ overexpression induced an increase in cell death resistance against both ADs (survival: AD198: 80±10% vs. 41±8% and AD288: 90±15% vs. 60±10% in NMuMG-PKCΔ and NMuMG-vector cells respectively). In order to evaluate the role of PI3K/Akt pathway in cell death resistance induced by both ADs, cells were treated with LY294002, a PI3K inhibitor. The inhibition of this signaling pathway in NMuMG-PKCΔ cells increased 3-fold AD198 cytotoxic effect, whereas did not alter AD288 effect. The role of NFκB signaling pathway in the resistance against cell death induced by each AD was determined by transient transfection with a variant of its repressor IκB. The inhibition of this signaling pathway significantly increased cell death susceptibility to both drugs (P&amp;lt;0.05 student's t test). In this work we have demonstrated that the anti-apoptotic signals generated by PKCΔ in NMuMG mammary cells could be reverted by inhibiting PI3K/Akt and/or NFκB signaling pathways. In addition, it was shown that the pathway involved was dependent on the mechanism of action of the cytotoxic drug used. 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 2142. doi:10.1158/1538-7445.AM2011-2142
1927-nm Fractional resurfacing of facial actinic keratoses: A promising new therapeutic option
Authors: Elliot T. Weiss, Jeremy A. Brauer, Robert Anolik, Kavitha K. Reddy, Julie K. Karen, Elizabeth K. Hale, Lori A. Brightman, Leonard Bernstein, Roy G. Geronemus
Journal: Journal of the American Academy of Dermatology (2012)
Patatin-like phospholipase domain containing 3 sequence variant and hepatocellular carcinoma
Authors: Stefano Ginanni Corradini, Maria Antonella Burza, Antonio Molinaro, Stefano Romeo
Journal: Hepatology (2011)

In a recent article in HEPATOLOGY, Valenti et al.1 reported an association of the patatin-like phospholipase domain containing 3 (PNPLA3) isoleucine-to-methionine substitution at position 148 (I148M; rs738409) with hepatitis C virus (HCV)-related chronic liver disease. In particular, they showed this genetic variant was associated with fatty liver and fibrosis progression in two independent cohorts of Caucasians with chronic HCV. In one study cohort, they also reported an independent association with hepatocellular carcinoma (HCC) in homozygous 148M carriers.1 Our goal was to examine the latter association in a cohort of individuals with HCV-related cirrhosis, comparing those with and without HCC. We genotyped a total of 221 (male/female = 141/80) Caucasians at the Department of Gastroenterology, "Sapienza" University of Rome, Italy, for the PNPLA3 148M allele. Inclusion criteria were presence of clinical cirrhosis, HCV RNA positivity, surveillance for HCC for at least 2 years, and alcohol consumption of <20 and <30 g/day for women and men, respectively. Mean age was 58 ± 11 years, 31% had diabetes, and 41% had radiological and/or histological diagnosis of HCC. We performed a multivariate analysis that included HCC as dependent variable and age, sex, diabetes, and the 148M genotype (148M homozygotes versus the other genotypes) as covariates. We found homozygosity for the 148M allele to be independently associated with HCC (odds ratio = 2.23, 95% confidence interval = 1.60-3.50, P = 0.008; Table 1). Liver disease is a spectrum of conditions deriving from the presence of chronic liver damage over many years. It ranges from simple hepatocellular damage, to liver inflammation, fibrosis, cirrhosis, and ultimately HCC. The PNPLA3 I148M variant has been previously associated with nonalcoholic2 as well as alcoholic liver disease.3 Valenti et al. showed for the first time an association of the 148M allele with HCV-related liver steatosis and fibrosis. They also found a possible link with HCC. Our results support the latter association. These data are consistent with the hypothesis of liver disease being a continuum of conditions where chronic stress acts on a genetically susceptible background, in a "two-hit" pathogenetic model. The PNPLA3 protein function remains mostly obscure, and at this time it is difficult to generate a hypothesis that may explain the association that was found. Longitudinal studies on HCV fibrosis progression and HCC onset are needed to confirm the PNPLA3 association, and functional studies are required to understand the mechanisms underlying it. Stefano Ginanni Corradini M.D., Ph.D.*, Maria Antonella Burza M.D.* , Antonio Molinaro M.D.*, Stefano Romeo M.D., Ph.D. , * Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy, Institute of Metabolic Science, University of Cambridge, Cambridge, UK, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
LINSEED OIL DERMATITIS
Authors: F. J. VOKOUN
Journal: JAMA (1927)

I began the study of linseed oil dermatitis when I was appointed industrial physician for the Sherwin Williams Company, paint manufacturers of Cleveland. In the manufacture of paint, linseed oil is an important factor. One of the plants of this company is devoted to the production of linseed oil, and it is in this plant that the cases were found.  For many years it was noticed that dermatitis was rife among the workers in the mill. The cases were usually mild—some of these persons had areas on the hands or feet which caused symptoms of itching or burning but were not severe enough to incapacitate them. However, soon after taking over the work from this plant I was confronted with three severe cases of dermatitis which necessitated keeping the men home from work. These cases were serious and brought the matter forcibly to my attention.  My recent preliminary paper 1
COLLOID CARCINOMA AT TWELVE YEARS OF AGE
Authors: J. A. Milne
Journal: BMJ (1905)

COLLOID CARCINOMA IN A CHILD.TL BmmA 925 illness, she discovered that she had an abdominal tumour, and coneulted me.I noted "small uterine fibroid, no trouble- some eymptoms, no bleeding."The period was regular, appearing every twenty-eight days.In the course of the year, after I examined the tumour, the show became more frequent, and small clots passed.In January, 1899, I found that the tumour was much enlarged, a lobule buiged into
Abstract 1555: TP53 oncomorphic mutations are associated with resistance to platinum- and taxol-based standard chemotherapy in advanced serous ovarian cancer patients
Authors: Pavla Brachova, Donghai Dai, Mathew Carlson, Michael Goodheart, Kristina Thiel, Eric Devor, Kimberly Leslie
Journal: Cancer Research (2014)

Abstract Mutations in the tumor suppressor gene TP53 abrogate the tumor suppressive functions of the p53 protein, and some mutations endow the mutant protein with oncogenic activity. These specific mutations we term oncomorphic. Many studies have attempted to correlate p53 mutation status with patient outcomes; however the results have been controversial due to indiscriminate categorization of all TP53 mutations into one group. Using advanced ovarian cancer as a model, our objective was to determine the relationship of oncomorphic TP53 mutations with the development of chemoresistance in advanced serous ovarian cancer patients uniformly treated with platinum and taxol primary chemotherapy. Clinical, genetic, and protein expression data from 264 high-grade serous ovarian cancer patients were downloaded from The Cancer Genome Atlas (TCGA) data portal. Associations between mutation types, chemoresistance, and progression-free survival (PFS) were calculated for patients harboring oncomorphic TP53 mutations, loss of function mutations, or unclassified mutations. Using a large and uniform patient population, we demonstrate the phenomenon of oncomorphic mutations in ovarian cancer. Specifically, patients with oncomorphic TP53 mutations showed significantly worse PFS when compared with patients with unclassified TP53 mutations (Log-rank, p &amp;lt; 0.05). Patients with oncomorphic TP53 mutations displayed higher rates of platinum resistance (X2, p = 0.0024) and an almost 60% higher chance of recurrence (HR=1.59, 95% confidence intervals 1.09, 2.33, p = 0.016). Furthermore, tumors containing oncomorphic TP53 mutations displayed a unique protein expression profile distinct from tumors with LOF or unclassified mutations. Taken together, these data reveal that particular oncomorphic TP53 mutations are highly associated with worse patient outcomes. Importantly, not all TP53 mutations are equal, and future studies should segregate mutations based on functional consequence. These data may have important implications for the future treatment of patients based on which TP53 mutation is present. Citation Format: Pavla Brachova, Donghai Dai, Mathew Carlson, Michael Goodheart, Kristina Thiel, Eric Devor, Kimberly Leslie. TP53 oncomorphic mutations are associated with resistance to platinum- and taxol-based standard chemotherapy in advanced serous ovarian cancer patients. [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 1555. doi:10.1158/1538-7445.AM2014-1555
Topical Tretinoin for Photoaged Skin
Authors: Patricio Pazmiño
Journal: JAMA (1988)

<h3>To the Editor.</h3> —I read with interest the article by Weiss et al<sup>1</sup>entitled "Topical Tretinoin Improves Photoaged Skin." The "Results" section of this study notes that 40 patients entered the study, but data are presented for only 30 patients. Ten patients apparently withdrew because of severe induced dermatitis or for personal reasons. The authors reported dermatitis as the only adverse reaction in 92% of the patients. Since it is possible that this dermatitis, which in some cases was severe, could be associated with a systemic absorption of tretinoin, I would like to know if drug absorption studies were done by Weiss et al and if any changes were noted in results of renal function tests, such as creatinine level and urinalysis, in the 40 patients. <h3>Report of a Case.</h3> —A 63-year-old man was referred for evaluation of abnormal creatinine clearance (1.23 mL/s [74 mL/min/m<sup>2</sup>]) and an increased
Therapeutic Antibody Gene Transfer: An Active Approach to Passive Immunity
Authors: Joost M. Bakker, Wim K. Bleeker, Paul W.H.I. Parren
Journal: Molecular Therapy (2004)

Advances in gene transfer approaches are enabling the possibility of applying therapeutic antibodies using DNA. In particular gene transfer in combination with electroporation is promising and can result in generating in vivo antibody concentrations in the low therapeutic range. However, several important problems need to be dealt with before antibody gene transfer can become a valuable supplement to the current therapies. As antibody production following gene transfer is difficult to control, the danger of inducing autoimmune conditions or uncontrollable side effects occurs in cases in which autologous antigens are targeted. It is suggested that the most promising area of application therefore appears to be infectious disease in which heterologous antigens are targeted and concerns for long-term antibody exposure are minimal. Finally, genes encoding fully human antibodies will enhance long-term expression and decrease problems linked to immunogenicity.
The effects of different bile salts on the absorption of fluid, electrolytes, and monosaccharides in the small intestine of the rat in vivo
Authors: J. T. Harries, G. E. Sladen
Journal: Gut (1972)

The effects of different bile salts on the absorption of fluid, electrolytes, and monosaccharides have been investigated in the rat small intestine in vivo. In the jejunum, deoxycholate (1 mM) impaired absorption of water and potassium, but not of sodium or glucose; at higher concentrations (2.5 and 5 mM) secretion of fluid and electrolytes occurred, and glucose and fructose absorption was impaired. By contrast, in the ileum, 1 mM deoxycholate failed to inhibit fluid and electrolyte absorption, and a concentration of 10 mM was required completely to inhibit absorption; secretion was not observed in the ileum. Chenodeoxycholate (5 mM) produced a similar effect to deoxycholate on fluid and electrolyte absorption in both jejunum and ileum, but taurocholate (5 mM) and taurodeoxycholate (5 mM) were ineffective.In jejunum, cholate, taurocholate, and taurodeoxycholate, each at a concentration of 5 mM, were less effective inhibitors of glucose transport than deoxycholate; chenodeoxycholate failed to inhibit glucose absorption. Deoxycholate produced histological damage at 5 mM, but not at lower concentrations. The functional and structural abnormalities were shown to be reversible phenomena. These findings may be relevant to the pathogenesis of diarrhoea in patients with bacterial overgrowth in the small intestine.
Ventilatory Control in Myxedema and Hypothyroidism
Authors: Clifford W. Zwillich, David J. Pierson, Fred D. Hofeldt, Edward G. Lufkin, John V. Weil
Journal: New England Journal of Medicine (1975)

Alveolar hypoventilation is known to occur in myxedema. To clarify the role of hypoxic ventilatory drive and hypercapnic ventilatory drive in thyroid hormone insufficiency states, 10 patients with myxedema and seven with hypothyroidism (thyroid ablation) were studied before and after thyroid replacement. An index developed for hypoxic ventilatory drive was markedly reduced in myxedema: 17 ± 4.7 (S.E.M.) (normal, 126 ± 8.7) (p < 0.01) and increased to 78 ± 12.6 (p = 0.02) with thyroid hormone replacement. In the hypothyroid group this index was also depressed as compared to normal at 67 ± 20 (p < 0.01) and increased to 114 ± 19 (p < 0.02) with replacement. An index for hypercapnic ventilatory drive was depressed in myxedema, 0.69 ± 0.13, as compared to a normal value of 1.88 ± 0.13 (p < 0.01), but was not significantly depressed in hypothyroidism. With thyroid hormone replacement this index did not significantly increase in either group. We conclude that both myxedema and hypothyroid states produce depression of hypoxic ventilatory drive that is responsive to replacement therapy. This alteration in ventilatory control may contribute to the hypoventilation seen in myxedema. (N Engl J Med 292:662–665, 1975)
393. Non-Viral Gene Transfer Using the Sleeping Beauty Transposon for Long-Term Gene Expression in the CNS of Neonatal Mice
Authors: Zachary L. Demorest, Walter C. Low, Andrew B. Freese, John R. Ohlfest
Journal: Molecular Therapy (2006)

Non-viral gene transfer might possibly treat enzyme deficiencies affecting the brain, due to secretion of the missing enzyme and metabolic cross correction. However, non-viral vectors generally suffer from poor gene transfer efficiency and transient gene expression. To overcome this limitation we used the Sleeping Beauty transposable element to achieve chromosomal integration and long- term expression of the luciferase reporter gene, and mannitol to increase gene delivery efficiency. Newborn mice were injected into the lateral cerebral ventricle with luciferase-transposon DNA conjugated with polyethylenimine (PEI) gene transfer reagent, with or without co-administration of SB-encoding DNA. In a second study, mannitol was administered intraperitoneally to newborn mice one hour before DNA administration. The brains were removed and assayed for luciferase activity (relative light units or RLUs). Animals injected with mannitol one hour before DNA/PEI injection revealed significantly higher luciferase expression at forty-eight hours than without mannitol (Fig. 1; p<0.05). Animals that received SB- encoding DNA showed significantly higher luciferase expression one month after injection than animals without SB (Fig. 1; p<0.05). Maximum long-term expression at one month was achieved when mannitol was administered prior to gene delivery with SB-encoding DNA to cause integration of the luciferase transgene (Fig. 1; average of 167,990 RLUs). These results demonstrate that mannitol pre- treatment combined with SB-mediated gene transfer achieves significant levels of long-term gene expression in the mammalian brain.
Thyroid hormone increases plasma cholesteryl ester transfer protein activity and plasma high-density lipoprotein removal rate in transgenic mice
Authors: J.A. Berti, M.E.C. Amaral, A.C. Boschero, V.S. Nunes, L.M. Harada, L.N. Castilho, H.C.F. Oliveira
Journal: Metabolism (2001)
Weight growth in infants born to mothers who smoked during pregnancy
Authors: V. Conter, I. Cortinovis, P. Rogari, L. Riva
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine whether maternal smoking during pregnancy causes impairment in growth after birth. <b>Design</b>: Longitudinal study. <b>Setting</b>: Six medical university centres of six towns of north, central, and south Italy. <b>Subjects</b>: 12987 babies (10238 born from non-smoking mothers, 2276 from mothers smoking one to nine cigarettes a day, and 473 from mothers smoking &gt;/=10 cigarettes a day) entered the study. <b>Main outcome measures</b>: Difference in weight gain between children born to smoking mothers and those born to non-smoking mothers. Weight was measured at birth and at 3 and 6 months of age. Maternal smoking habit was derived from interview on third or fourth day after delivery. <b>Results</b>: Compared with children born to mothers who did not smoke during pregnancy, the birth weights of children born to mothers who smoked up to nine cigarettes a day were 88 g (girls) and 107 g (boys) lower; in children born to mothers who smoked &gt;/=10 cigarettes a day weights were 168 g and 247 g lower. At six months of age for the first group the mean weight for girls was 9 g (95% confidence interval -47 g to 65 g) higher and for boys 64 g (-118 g to -10 g) lower than that of children born to mothers who did not smoke. The corresponding figures for the second group were 28 g (-141 g to 85 g) lower for girls and 24 g (-136 g to 88 g) lower for boys. <b>Conclusions</b>: The deficits of weight at birth in children born to mothers who smoked during pregnancy are overcome by 6 months of age. These deficits are probably not permanent when smoking habit during pregnancy is not associated with other unfavourable variables (such as lower socioeconomic class). <h3>Key messages</h3> Key messages The issue of weight growth in babies born to smoking mothers remains controversial Data obtained in this study confirm the association of smoking during pregnancy with lower birth weight The reduction of weight at birth, however, may be completely overcome by 6 months of age
Effect of Follicle-Stimulating Hormone on Ovarian Androgen Production in a Woman with Isolated Follicle-Stimulating Hormone Deficiency
Authors: Randall B. Barnes, Robert L. Rosenfield, Anne Namnoum, Lawrence C. Layman
Journal: New England Journal of Medicine (2000)

Clopidogrel and Thrombotic Thrombocytopenic PurpuraTo the Editor: Clopidogrel is indicated for the reduction of atherosclerotic events (myocardial infarction, stroke, and death from vascular causes) in patients with atherosclerosis documented by recent stroke, recent myocardial infarction, or established peripheral arterial disease.This indication is based on the results of a clinical trial, involving 19,185 patients, in which clopidogrel was compared with aspirin in patients at risk for ischemic events.The study's steering committee estimated that clopidogrel would prevent about 24 major clinical events for every 1000 patients treated for one year. 1 Clopidogrel was approved by the Food and Drug Administration (FDA) in November 1997 and has been used in more than 3 million patients worldwide.Bennett et al. (June 15 issue) 2 describe 11 suspected cases of clopidogrelassociated thrombotic thrombocytopenic purpura.Information on these cases was obtained through solicited or spontaneous reporting or from published reports.Several of these suspected cases involve concomitant conditions, medications previously reported to be associated with thrombotic thrombocytopenic purpura, or both, and a clear causal relation with the use of clopidogrel could not be established in some of the cases.Nevertheless, Sanofi-Synthelabo and Bristol-Myers Squibb have included all suspected cases of thrombotic thrombocytopenic purpura in any estimates of incidence.Sanofi-Synthelabo and Bristol-Myers Squibb had reported these cases to worldwide regulatory authorities be-fore they were reported in the Journal, and on the basis of these cases, the FDA has approved new labeling for clopidogrel, which includes information on thrombotic thrombocytopenic purpura.The report by Bennett et al. highlights the importance of post-marketing safety reporting in the detection of rare adverse events.Both Sanofi-Synthelabo and Bristol-Myers Squibb are committed to continued surveillance of these events and are evaluating the best methods for gaining a better understanding of thrombotic thrombocytopenic purpura and the incidence of this rare event.
Use of historical controls for animal experiments.
Authors: T Yanagawa, D G Hoel
Journal: Environmental Health Perspectives (1985)

Statistical methods for the use of historical control data in testing for a trend in proportions in carcinogenicity rodent bioassays are reviewed. Asymptotic properties of the Hoel-Yanagawa exact conditional tests are developed and compared with the Tarone test. It is indicated that the Hoel-Yanagawa test is more powerful than the Tarone test. These tests depend on the beta-binomial parameters which are estimated from historical data. The goodness of fit of beta-binomial distributions to historical data is illustrated by application to the historical control database in the National Toxicology Program. Finally, sensitivities of the exact conditional test to the historical information is discussed and a conservative use of the test is considered.
CHRONIC BLADDER IRRITATION IN FEMALES
Authors: H. A. O'Brien
Journal: JAMA (1953)

Bladder trouble is extremely common in females of any age. In most of our patients with this complaint, we found the cause to be a simple infection in the urethra and trigone. To accurately determine the frequency of this lesion in our practice, we analyzed the records of 200 consecutive female patients seen for the first time in the office. It showed that in 74.5% the symptoms resulted from primary disease in the urethra and trigone. The remaining 24.5% had a variety of urinary tract disorders as seen in a general urologic practice. These were diagnosed as urethritis and trigonitis, 149 patients (74.5%); kidney and ureter stones, 23 (11.5% ); acute and chronic pyelonephritis, 9 (4.5% ); solitary renal cyst, 3 (1.5%); cystocele, urethrocele, or procidentia, 2 (1% ); ureteral stricture and tumor, 2 (1%); exstrophy of bladder, 1 (0.5%); carcinoma of bladder, 4 (2%); ureterocele with hydronephrosis, 1 (0.5%); nephroptosis, 1 (0.5%);