tbuckley/cabot-search huggingface dataset:
Biokinetics and Subchronic Toxic Effects of Oral Arsenite, Arsenate, Monomethylarsonic Acid, and Dimethylarsinic Acid in v-Ha- <i>ras</i> Transgenic (Tg.AC) Mice
Authors: Yaxiong Xie, Kevin J. Trouba, Jie Liu, Michael P. Waalkes, Dori R. Germolec
Journal: Environmental Health Perspectives (2004)

Previous research demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment increased the number of skin papillomas in v-Ha-ras transgenic (Tg.AC) mice that had received sodium arsenite [(As(III)] in drinking water, indicating that this model is useful for studying the toxic effects of arsenic in vivo. Because the liver is a known target of arsenic, we examined the pathophysiologic and molecular effects of inorganic and organic arsenical exposure on Tg.AC mouse liver in this study. Tg.AC mice were provided drinking water containing As(III), sodium arsenate [As(V)], monomethylarsonic acid [(MMA(V)], and 1,000 ppm dimethylarsinic acid [DMA(V)] at dosages of 150, 200, 1,500, or 1,000 ppm as arsenic, respectively, for 17 weeks. Control mice received unaltered water. Four weeks after initiation of arsenic treatment, TPA at a dose of 1.25 microg/200 microL acetone was applied twice a week for 2 weeks to the shaved dorsal skin of all mice, including the controls not receiving arsenic. In some cases arsenic exposure reduced body weight gain and caused mortality (including moribundity). Arsenical exposure resulted in a dose-dependent accumulation of arsenic in the liver that was unexpectedly independent of chemical species and produced hepatic global DNA hypomethylation. cDNA microarray and reverse transcriptase-polymerase chain reaction analysis revealed that all arsenicals altered the expression of numerous genes associated with toxicity and cancer. However, organic arsenicals [MMA(V) and DMA(V)] induced a pattern of gene expression dissimilar to that of inorganic arsenicals. In summary, subchronic exposure of Tg.AC mice to inorganic or organic arsenicals resulted in toxic manifestations, hepatic arsenic accumulation, global DNA hypomethylation, and numerous gene expression changes. These effects may play a role in arsenic-induced hepatotoxicity and carcinogenesis and may be of particular toxicologic relevance.
HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER
Authors: F. S. Robscheit-Robbins, G. H. Whipple
Journal: The Journal of Experimental Medicine (1933)

Biological assay of human liver material shows various concentrations of hemoglobin producing material in various diseased states. Cardiac congestion with red atrophy of the liver shows values (Table 21) somewhat below the human normal—94 per cent compared to 162 per cent. It is probable that this is due to atrophy and destruction of the liver cells in the centers of the liver lobules. We believe the remaining liver cells have a normal content of hemoglobin producing factors. Amyloid (tuberculosis) and fatty (alcoholic) degeneration show (Table 22) subnormal values—111 per cent compared to 162 per cent. If we allow for the "dilution" of liver cell weight by the amyloid and fat we observe normal values for the concentration of hemoglobin producing factors. Carcinoma growth in the liver whether primary or secondary shows net figures (Table 23) which are low—75 per cent compared to normal 162 per cent. It appears that cancer tissue, even tumor cells originating from hepatic epithelium, contains no hemoglobin producing factors. If we allow for the "dilution" of the remaining liver cells by the cancer tissue the figures are within normal limits. Cirrhosis and hepatitis (Table 24) with no signs of true hepatic insufficiency or severe hepatic injury but death supervening from secondary infection or hemorrhage will give average normal values –164 per cent compared to normal human of 162 per cent. Icterus is not a factor. Cirrhosis or hepatitis with severe parenchyma injury and signs of hepatic insufficiency give low values (Table 25) in biological assay –48 per cent compared to normal human 162 per cent. It may be surprising that the liver cells hold so tenaciously to these unknown factors influencing hemoglobin production but obviously only in severe liver injury is this concentration seriously reduced.
Abstract 3488: Targeting ligands and nanotherapeutics against acute myeloid leukemia stem cell
Authors: Hongyong Zhang, Juntao Luo, Yuanpei Li, Paul T Henderson, Yanchun Wang, Sebastian Wachsmann-Hogiu, Kit S. Lam, Chongxian Pan
Journal: Cancer Research (2012)

Abstract Background: Acute myeloid leukemia (AML) stem cells (LSC) can survive the conventional-dose chemotherapy, generate more differentiated leukemic cells and cause recurrence. In order to cure AML, LSC must be eradicated. This project was to develop targeting therapeutics to overcome chemoresistance and eradicate LSC. Materials and Methods: The phage-display library was panned to identify ligands targeting C-type lectin-like molecule-1 (CLL1) expressed on LSC, but not on normal hematopoietic stem cells. A CLL1-targeting ligand was used to decorate the surface of micelle nanocarrier developed by our group to deliver chemotherapeutic drugs to LSC. Target-specific drug delivery was determined using A549 adherent cells expressing CLL1 and CD34+CD38- leukemia cells freshly isolated from clinical specimens. Toxicology study was performed in Balb/c mice. Results: After three rounds of panning against A549 cells expressing CLL1, 35 out of 36 clones contained the same amino acid motif LR(S/T). These ligands did not bind to any peripheral blood cells and normal hematopoietic stem cells. One ligand named CLL1-L1 was used to decorate the surface of nanomicelles loaded with chemotherapeutic drug daunorubicin (DNR). These targeting nanomicelles were approximately 15 nm in diameter. The loading capacity was around 5 mg of daunorubicin per 20 mg of nanomicelle, a clinically useful degree of drug loading. High-resolution tomography showed that targeting nanomicelles delivered the drug load directly to the intracellular space including nucleus much more efficiently than the non-targeting nanomicelles (p&amp;lt;0.05). These targeting nanomicelles could deliver the drug load to CD34+CD38- leukemic cells (containing LSC) isolated from clinical specimens, but did not bind to normal blood or normal hematopoietic stem cells. Chemotheapeutic drug formulated in these nanomicelles is about three times less toxic than the parental free drug, suggesting this nanoformulation may allow administration of high-dose chemotherapy without the associated severe toxicity. Conclusion: This is the first report on the development of targeting ligands and nanotherapeutics against AML stem cells. Nanomicelles decorated with CLL1-targeting peptides can potentially deliver high-dose chemotherapeutic drugs directly into LSC and eradicate this cell population, in addition to treating leukemic cells throughout the body and decreasing toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3488. doi:1538-7445.AM2012-3488
The Novel Tumor Suppressor p33ING2 Enhances Nucleotide Excision Repair via Inducement of Histone H4 Acetylation and Chromatin Relaxation
Authors: Jing Wang, Mei Yieng Chin, Gang Li
Journal: Cancer Research (2006)

Abstract p33ING2 is a novel candidate tumor suppressor, which has been shown to be involved in the regulation of gene transcription, cell cycle arrest, and apoptosis in a p53-dependent manner for maintaining the genomic stability. Previously, we showed that p33ING2 promoted UV-induced apoptosis in human melanoma cells. To further reveal the role of p33ING2 in cellular stress response to UV irradiation, we hypothesized that p33ING2 may enhance the repair of UV-damaged DNA, similarly to its homologue p33ING1b. Using the host-cell reactivation assay, we show that overexpression of p33ING2 significantly enhances nucleotide excision repair of UV-induced DNA damage in melanoma cells in a p53-dependent manner. Furthermore, DNA repair is completely abolished in cells treated with p33ING2 small interfering RNA, suggesting that a physiologic level of p33ING2 is required for nucleotide excision repair. In addition, we found that p33ING2 is an essential factor for UV-induced rapid histone H4 acetylation, chromatin relaxation, and the recruitment of damage recognition protein, xeroderma pigmentosum group A protein, to the photolesions. These observations suggest that p33ING2 is required for the initial DNA damage sensing and chromatin remodeling in the nucleotide excision repair process. (Cancer Res 2006; 66(4): 1906-11)
Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers.
Authors: J L Madara, J Stafford
Journal: Journal of Clinical Investigation (1989)

Although epithelia, which often are in intimate contact with lymphoid cells, may bear receptors for various cytokines, it is unclear whether cytokines directly effect epithelial function. We examine the effects of the cytokine interferon (IFN) on barrier function of cultured monolayers of the T84 human intestinal epithelial cell line. Gamma IFN, in concentrations and exposures required to show its other biological effects, directly affects such monolayers. Monolayer resistance is substantially diminished by gamma IFN. Such effects were not due to cytotoxicity as judged morphologically and by LDH assays. Solute fluxes and dual Na+-mannitol flux analysis indicate that the resistance decrease is due to an effect of gamma IFN on tight junction permeability. The effects of gamma IFN on monolayer barrier function were not duplicated by the cytokines interleukin 1, interleukin 2, or tumor necrosis factor. We speculate that such products of activation of lymphoid cells might influence barrier function of intestinal, and perhaps other epithelia in disease states.
Network modeling links breast cancer susceptibility and centrosome dysfunction
Authors: Miguel Angel Pujana, Jing-Dong J Han, Lea M Starita, Kristen N Stevens, Muneesh Tewari, Jin Sook Ahn, Gad Rennert, Víctor Moreno, Tomas Kirchhoff, Bert Gold, Volker Assmann, Wael M ElShamy, Jean-François Rual, Douglas Levine, Laura S Rozek, Rebecca S Gelman, Kristin C Gunsalus, Roger A Greenberg, Bijan Sobhian, Nicolas Bertin, Kavitha Venkatesan, Nono Ayivi-Guedehoussou, Xavier Solé, Pilar Hernández, Conxi Lázaro, Katherine L Nathanson, Barbara L Weber, Michael E Cusick, David E Hill, Kenneth Offit, David M Livingston, Stephen B Gruber, Jeffrey D Parvin, Marc Vidal
Journal: Nature Genetics (2007)
Characteristic features of cockroach hypersensitivity in Turkish asthmatic patients
Authors: D. Mungan, G. Çelik, B. Sin, S. Bavbek, Y. Demirel, Z. Misirligil
Journal: Allergy (1998)

Exposure to cockroach has been reported to cause asthma in many parts of the world. Although house‐dust‐mite is known to be the most important indoor allergen in Turkey, there are few data on the prevalence of allergy t o cockroaches. Therefore, we evaluated the prevalence of cockroach sensitivity in asthmatic TUrkish patients to see whether it is also an important source of asthma in addition to house‐dust mites. A total of 206 patients demonstrating the characteristic features of asthma were included in the study. Sixty‐three percent of the patients were considered atopic, and 37% were found to be nonatopic by skin prick tests. Mite allergens were the most common cause of indoor allergy (50%), while cockroach sensitivity was detected in 25.7% of all the asthmatics. Among all cockroach‐sensitive patients, 70% were also positive for mites. A female predominance was observed in cockroach‐sensitive patients, as 44% of atopic women and 34% of atopic men had positive skin tests with cockroach allergen. The average duration of asthma was 7.1+5.6 years in cockroach‐sensitive asthmatics, and there was no difference between groups in average duration of asthma (P&gt;0.05). Mild, moderate, and severe asthmatics constituted 73.6%, 20.7%. and 5.7% of the cockroach‐sensitive patients, respectively. These data indicate that cockroach is also an important source of domestic infestation n i Tlirkey. Thus, it seems reasonable to suggest the need for cockroach allergen in the routine battery of inhalant skin tests in this geographic location. However, possible cross‐reactivity with mites has to be taken into consideration during the clinical evaluation of subjects with cockroach sensitivity, especially in our patient population with such high rates of house‐dust‐mite allergy.
The Debut of Dueling Viewpoints
Authors: Phil B. Fontanarosa
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Control of Neoplastic Effusions
Authors: Augustus Gibson
Journal: JAMA (1961)

<h3>To the Editor:—</h3> InThe Journal(<b>176</b>:747 [May 27] 1961) there is a question concerning new treatments for metastatic carcinoma of the pleura. I do not question the validity of the reply, but I believe it might have been desirable to mention the possible use of quinacrine ( Atabrine) hydrochloride in the control of neoplastic effusions. This has been reported by Gellhorn, et al. (<i>Dis Chest</i><b>39</b>:165-176 [Feb.] 1961). While the number of cases reported has been relatively small, it does appear that quinacrine is effective in controlling neoplastic effusions and while its use is not unattended by side reactions, the drug has the advantage of lack of toxicity to the blood forming organs and does not involve the hazards of the radioactive isotopes.
The Relation Between Vaginal Spermicides and Congenital Disorders
Authors: Samuel Shapiro
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Recently, Bracken<sup>1</sup>has added yet another compelling argument challenging the validity of the findings that suggest that spermicides cause selected birth defects. It remains to be pointed out, however, that Jick et al<sup>2</sup>have evaded the central challenge raised by Dr Watkins' letter,<sup>3</sup>namely, that without further evaluation of their findings they should not have published them at all: had they reclassified all "exposed" noncases as well as cases (as they suggested),<sup>2</sup>they would very likely no longer have had adequate statistical power, and there would have been nothing to publish. In addition, Dr Watkins hinted in his letter<sup>3</sup>and has explicitly testified in court<sup>4</sup>that at least one of the investigators was made aware of the problem of misclassification of exposure status before the findings were submitted for publication. The authors now have the choice either to take the step
Acetylcholinesterase-Containing Nerve Fibers in the Canine Kidney
Authors: OLIVIA C. MCKENNA, EVANGELOS T. ANGELAKOS
Journal: Circulation Research (1968)

The distribution of acetylcholinesterase in the canine kidney was studied by the histochemical method of Karnovsky and Roots and compared to the distribution of adrenergic fibers studied with the fluorescence histochemical method of Falck and Hillarp. Specific inhibitors of nonspecific cholinesterase and acetylcholinesterase were used to differentiate between the two enzymes. In the hilus, acetylcholinesterase-containing nerve fibers were found in large bundles lying adjacent to the media of the hilar arteries. In the rest of the kidney, these fibers traveled with the interlobar, arcuate, and interlobular arteries, the afferent arterioles, and the vasa recta in the outer medulla. The outermedullary nerves appeared to originate in the arcuate connective tissue sheath. Acetylcholinesterase-containing nerve fibers were not seen in association with any other structures. The distribution was similar to that of adrenergic fibers although the density of the acetylcholinesterase-containing fibers was less. Two weeks after unilateral renal denervation, no adrenergic nerve fibers could be detected histochemically in the denervated kidney, whereas acetylcholinesterase-containing nerve fibers were found in five out of seven kidneys. Acetylcholinesterase-staining ganglion cells found in the hilus of the unsuccessfully denervated kidneys appeared to be the source of the acetylcholinesterase-containing nerves. On the basis of these observations, it may be concluded that the kidney is innervated by acetylcholinesterase-containing nerves which are independent of the adrenergic nerve supply.
Antibiotics and Gram-Negative Bacteremia
Authors: Joseph T. Curti
Journal: JAMA (1975)

AN ARTICLE appeared in the March 4 issue ofThe Journalpurporting to link the alleged overprescribing of antibiotics with "new and major hazards" to public health.<sup>1</sup>The misuse and overuse of antibiotics, the article claimed, has resulted in recent dramatic increases in the incidence and mortality of Gram-negative bacteremia. The authors cite an estimate of "as many as 300,000 episodes and more than 100,000 fatalities from Gram-negative bacteremia"<sup>2</sup>annually. The authors also quote from an editorial in<i>The Journal of Infectious Diseases</i>attributing "a minimum of 50,000 deaths" to Gram-negative bacteremia,<sup>3</sup>and suggest that the United States is presently in the throes of a "full-blown national epidemic." The implication that antibiotics are the sole factor in the rising incidence of Gram-negative bacteremia and death is hardly credible in the light of the many complex variables involved in the etiology and treatment of Gram-negative infections. This article
Contrast enhanced ultrasound (US) is an accurate technique to evaluate the efficacy of ablation treatments for hepatocellular carcinoma (HCC)
Authors: L. Riccardi, M. Pompili, R. Orefice, M.E. Lippi, B. Barbaro, R. Picconi, F. Elia, B. Alfei, A. Grieco, A. Cedrone, G. Gasbarrini, G.L. Rapaccini
Journal: Journal of Hepatology (2003)
Pleuropneumonia and Alkaline Phosphatase
Authors: MAJED M. ODEH
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 April 1988Pleuropneumonia and Alkaline PhosphataseMAJED M. ODEH, M.D., HARRY M. BASSAN, M.D.MAJED M. ODEH, M.D.Search for more papers by this author, HARRY M. BASSAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-4-644_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor; The association of serum alkaline phosphatase elevation with severe extrahepatic infection is well documented. In such cases, the serum bilirubin is also moderately elevated, with a mild rise in serum alkaline phosphatase and transaminase levels, which correlates with hepatic impairment. We report a case of pleuropneumonia associated with a marked rise in serum alkaline phosphatase, with normal serum bilirubin and transaminase levels, and normal liver biopsy findings. To the best of our knowledge, a similar case has not been reported previously.A 68-year-old woman was admitted with a 5-day history of fever, cough, left lower chest pain,...References1. WOLF P. Clinical significance of an increased or decreased serum alkaline phosphatase. Arch Pathol Lab Med. 1978;102:497-501. MedlineGoogle Scholar2. RASMUSONBJORKDAMBER TGL. Tumor markers in bronchogenic carcinoma: an evaluation of carcinoembryonic antigen, tissue polypeptide antigen, placental alkaline phosphatase and pseudouridine. Acta Radiol [Oncol]. 1983;22:209-14. CrossrefMedlineGoogle Scholar3. FANGGINSBERGDOBBINS MAW. Marked elevation in serum alkaline phosphatase activity as a manifestation of systemic infection. Gastroenterology. 1980;78:592-7. CrossrefMedlineGoogle Scholar4. CHULIAW CY. High serum alkaline phosphatase in septemic infection. Gastroenterology. 1980;79:776. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Haifa City Medical Center (Rothschild) and Technion Faculty of Medicine Haifa 31048, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByTransient Hyperphosphatasaemia in An Adult with Pre-Existing Liver DiseaseTransient Alkaline Hyperphosphatasaemia in an Adult: Biochemical PeculiaritiesInterpretation and Clinical Significance of Alkaline Phosphatase Isoenzyme Patterns 1 April 1988Volume 108, Issue 4Page: 644-644KeywordsAminotransferasesBilirubinBiopsyFeversIschemiaLiverPhosphatases Issue Published: 1 April 1988 PDF DownloadLoading ...
Bone mineral density in patients with type 1 and type 2 diabetes.
Authors: J T Tuominen, O Impivaara, P Puukka, T Rönnemaa
Journal: Diabetes Care (1999)

OBJECTIVE: To assess the effect of type 1 and type 2 diabetes and insulin treatment on bone mineral density (BMD) in middle-aged and elderly men and women. RESEARCH DESIGN AND METHODS: We measured BMD and evaluated known determinants of osteoporosis in 56 type 1 and 68 type 2 diabetic patients and 498 nondiabetic community control subjects. All patients, aged 52-72 years, developed diabetes after the age of 30 years (i.e., after achievement of peak bone mass) and were treated with insulin. BMD was measured at the proximal femur with dual-energy X-ray absorptiometry. RESULTS: Among both sexes, BMD values were significantly lower in type 1 diabetic patients than in type 2 diabetic patients or the control subjects. When adjusted for age and BMI, the differences between type 1 diabetic patients and control subjects remained essentially unchanged in both sexes, whereas the differences between type 1 and type 2 diabetic subjects were significant only in men. After further adjustments for confounding factors, the average BMD values were still lower in type 1 diabetic subjects than in type 2 diabetic subjects although with lesser significance. Past low-energy fractures were more common in type 1 diabetic women than in type 2 diabetic women. CONCLUSIONS: The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes. This cannot be explained by insulin treatment, which was prescribed for both types of patients. Because the causes of low BMD in type 1 diabetes are unknown, these patients should be evaluated for the risk of osteoporosis and related fractures and offered appropriate preventive measures.
Coma Associated with Vincristine Therapy
Authors: J. A. Whittaker, D. H. Parry, C. Bunch, D. J. Weatherall
Journal: BMJ (1973)

Three cases of coma after vincristine therapy are described. One patient had hyponatraemia and other features of inappropriate secretion of antidiuretic hormone. The effects were temporary, and full recovery occurred in all three patients.
A Case Against Something That Is Not the Case: The Groningen Protocol and the Moral Principle of Non-Maleficence
Authors: Martine C. de Vries, A. A. Eduard Verhagen
Journal: The American Journal of Bioethics (2008)

Discussions about the initiation and continuation of treatment in newborns with serious medical conditions are one of the most difficult aspects of pediatric practice. Although technological develo...