tbuckley/cabot-search huggingface dataset:
Abstract 1814: Claudin-3 and claudin-4 regulate sensitivity to cisplatin by controlling expression of the copper and cisplatin influx transporter CTR1
Authors: Xinjian Lin, Xiying Shang, Gerald Manorek, Stephen Howell
Journal: Cancer Research (2012)

Abstract Cell adhesion complexes play a central role in controlling the behavior of epithelial cells, and loss of cell-cell adhesion is a characteristic of virtually all epithelial malignancies. Claudin-3 (CLDN3) and claudin-4 (CLDN4) are the major structural molecules that form tight junctions between epithelial cells. We found that knockdown of the expression of either CLDN3 or CLDN4 produced marked changes in the phenotype of ovarian cancer cells including an increase in in vivo growth rate and metastatic potential. However, the role of claudins in controlling sensitivity of ovarian cancer cells to the platinum-containing drugs, and the mechanisms by which they regulate the sensitivity, remain largely unknown. The effect of CLND3 and CLDN4 on cisplatin cytotoxicity, cellular accumulation and DNA adduct formation was compared in the CLDN3- and CLDN4-expressing parental human ovarian carcinoma 2008 cells and CLDN3 or CLDN4 knockdown sublines (CLDN3KD and CLDN4KD, respectively). CLDN3KD cells were 3.1-fold resistant to cisplatin whereas CLDN4KD cells were 8.0-fold resistant compared to the parental 2008 cells. The net accumulation of platinum in CLDN3KD and CLDN4KD cells was reduced to 66% and 49% of that in the parental cells after exposure to 30 μM cisplatin for 1 h. Likewise, the DNA adduct levels dropped to 65% and 41% of control when CLDN3 and CLDN4 were knocked down. Given that transporters and chaperones that manage copper homeostasis regulate platinum drug accumulation and efflux, their expression was measured by qRT-PCR. Among these, only the expression of CTR1 was significantly reduced (p&amp;lt;0.01) in the knockdown cells while there was no appreciable change in CTR2, ATP7A, ATP7B or ATOX1 mRNA levels. Consistent with the decrease in CTR1 level, the average steady-state copper level in the 2008 cells was 6.4 ± 1.26 ng Cu/μg S whereas the CLDN3KD and CLDN4KD cells contained only 4.2 ± 0.87 and 4.0 ± 0.74 ng Cu/μg S resulting in a 34% (p=0.008) and 38% (p=0.004), respectively, loss of intracellular copper. Copper-dependent tyrosinase activity was also markedly reduced in those CLDN knockdown cells when incubated with the substrate L-DOPA. These results indicate that CLDN3 and CLDN4 affect sensitivity to the cytotoxic effect of cisplatin by regulating expression of the copper transporter CTR1 that we have previously shown to play a central role in the influx of cisplatin. 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 1814. doi:1538-7445.AM2012-1814
Hb bicětre or α<sub>2</sub>β<sub>2</sub>63(E7)His → pro in a white male: Clinical observations over a period of 25 years
Authors: D. R. Miller, J. B. Wilson, A. Kutlar, T. H. J. Hulsman
Journal: American Journal of Hematology (1986)

Abstract A description is given of clinical observations over a period of 25 years for a 26‐year‐old white male with a heterozygosity for the β‐chain variant, Hb Bicětre, in which β63His is replaced by Pro. The variant was identified through analysis of tryptic peptides from a digest of the β X ‐chain isolated by PCMB precipitation and purified by chromatography. Similarity between the clinical histories of the first (French) heterozygote and our patient was most striking, including improvement after splenectomy.
Repetitive Ventricular Tachyarrhythmia: Result Of Pacemaker Failure
Authors: James Devorss
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The use of the demand feature in pacemakers has reduced, but not eliminated, problems of arrhythmias.<sup>1</sup>Premature battery depletion and failure of electronic components have continued to be significant problems. We observed an early and unexpected manifestation of pacemaker failure, which was permitted to continue primarily due to a low "threshold" of suspicion, and an unfortunate attitude of faith that the situation would improve. <h3>Report of a Case.—</h3> A 64-year-old man complained of increasing fatigue, dyspnea on exertion, and orthopnea. No history of angina pectoris, myocardial infarction, or rhythm disturbance could be elicited. Findings included the following: blood pressure (BP), 130/70 mm Hg; pulse rate, 45 beats per minute; cannon waves in the jugular veins; a systolic ejection murmur; and an increase in the transverse diameter of the heart by x-ray film. An electrocardiogram revealed normal sinus rhythm, complete heart block, and idioventricular rhythm at a
Abstract 2705: Novel functions of the homeoprotein SIX2 in mediating anchorage independence and metastasis in breast cancer.
Authors: Chu-An Wang, Paul Jedlicka, Vadym Zaberezhnyy, Aik-Choon Tan, Heide Ford
Journal: Cancer Research (2013)

Abstract Homeobox genes encode for transcription factors that are master regulators of embryogenesis, and their misexpression has been implicated in multiple cancers. The role of the homeoprotein Six2 in developing kidney has been well demonstrated; however, its role in cancer progression is largely unknown. Here, we demonstrate, for the first time, that Six2 is causally involved in mammary tumor progression. When Six2 is knocked down (KD) in the 66cl4 mammary carcinoma cells, lung metastasis is significantly decreased compared to control KD; however, Six2 KD conferred no significant effect on growth of the primary tumor or on tumor-associated angiogenesis/lymphangiogenesis, in contrast to its closely related family member, Six1, which has been implicated in all the aforementioned properties; suggesting that Six2 may participate in later stages of the metastatic cascade. Expression of Six2 in the 4TO7 mammary carcinoma cell line (a cell line that is syngeneic with 66cl4, but expresses very low levels of endogenous Six2) led to changes in cell morphology, increased growth in soft agar, increased resistance to anoikis, and significantly enhanced lung metastasis in Balb/c mice. To determine the mechanism by which Six2 mediates metastasis, microarray analysis was performed on 4TO7-control and Six2 expressing cells. Interestingly, genes which have been implicated in lung metastasis (MMP, ANGPTL4, VCAM1) are significantly up-regulated in Six2 overexpressing 4TO7 cells; while the epithelial marker, E-Cadherin, is dramatically decreased. Finally, analysis of SIX2 expression from public microarray datasets indicates that SIX2 is increased in breast cancers compared to normal breast tissue. In addition, high expression of SIX2 correlates with poor prognosis (distant metastasis free survival, overall survival and relapse free survival) in 1881 human breast tumors examined using the GOBO (Gene Expression-Based Outcome for Breast Cancer Online) database, and upon further investigation we found that SIX2 expression is particularly associated with poor prognosis in luminal A, normal-like and ER-positive breast tumors. Together, our studies define a novel role of Six2 in breast cancer metastasis. Citation Format: Chu-An Wang, Paul Jedlicka, Vadym Zaberezhnyy, Aik-Choon Tan, Heide Ford. Novel functions of the homeoprotein SIX2 in mediating anchorage independence and metastasis in breast cancer. [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 2705. doi:10.1158/1538-7445.AM2013-2705
Conversion of Micronodular Cirrhosis into Macronodular Cirrhosis
Authors: Lis Fauerholdt, Poul Schlichting, Erik Christensen, Hemming Poulsen, Niels Tygstrup, Erik Juhl
Journal: Hepatology (1983)

The conversion from micro- to macronodular cirrhosis is claimed to be a general phenomenon. In this study, the conversion was quantitated by means of liver needle follow-up biopsies and autopsy in 156 patients followed in a controlled clinical trial of prednisone treatment in cirrhosis. In the initial biopsy, 75 patients were classified as micronodular cirrhosis, and of them, 68 had macronodular cirrhosis at autopsy indicating a conversion ratio of about 0.9 in 10 years. This may overestimate the true conversion ratio slightly since conversion in many cases only was demonstrated at autopsy where the diagnosis of macronodular cirrhosis is made with greater certainty than from a needle biopsy. The median time interval between the diagnosis of micro- and macronodular cirrhosis was 2.25 years which is a maximum estimate of the conversion time due to irregular spacing between biopsies (or biopsy and autopsy). No significant difference was found between the conversion time in females and males. The conversion was faster in patients not drinking alcohol compared to patients drinking alcohol, but the difference was not significant. Prednisone treatment tended to accelerate the conversion, but not significantly.
Phospholipid Synthesis by Mammalian (Rabbit) Lung Tissue.
Authors: Henry O. Heinemann
Journal: Annals of Internal Medicine (1966)

s1 May 1966Phospholipid Synthesis by Mammalian (Rabbit) Lung Tissue.Henry O. Heinemann, M.D., Sue Buckingham, M.D., Sheldon C. Sommers, M.D.Henry O. Heinemann, M.D.Search for more papers by this author, Sue Buckingham, M.D.Search for more papers by this author, Sheldon C. Sommers, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1180_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is now apparent that the mammalian lung is not solely concerned with the physical-chemical process of gas exchange but has other, nonrespiratory, functions. One of these functions, which has attracted considerable interest in recent years, is the synthesis of lipids. The ability of lung tissue to synthesize lipids has been established by a variety of investigators in the rat, rabbit, dog, and guinea pig. In vivo and in vitro studies in rabbits utilizing various radioactive isotope-labeled precursors have demonstrated that lung tissue can utilize glucose, lactate, pyruvate, palmitate and especially acetate for the preferential formation of phospholipids, specifically lecithin.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Henry O. Heinemann, M.D.; Sue Buckingham, M.D.; Sheldon C. Sommers, M.D.Affiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1180-1180KeywordsGlucoseGuinea pigsLactatesLipidsLungsPhospholipidsPyruvateRabbits ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Continuing Medical Education
Authors: Dennis K. Wentz
Journal: JAMA (1992)

EVENTS in 1991 and 1992 reflected continuing widespread debate about the form continuing medical education (CME) should take, who should provide it, the role commercial companies should play in paying for it, and how successful completion of specific CME activities should be documented. The American Medical Association (AMA) House of Delegates reviewed the Physician's Recognition Award (PRA) certification requirements and referred questions concerning the requirements to the AMA Board of Trustees for decision. A number of CME organizations joined to develop voluntary standards for industry funding of CME and rules for disclosure of conflict of interest by CME faculty. The Food and Drug Administration (FDA) took an interest in industry relationships to CME—the first time the federal government has taken a major interest in CME management. The AMA and the American Hospital Association developed a form that CME providers can use to document physician participation in activities directed toward expanding
AN INVESTIGATION INTO THE SIGNIFICANCE OF HORMONAL FACTORS IN EXPERIMENTAL POLIOMYELITIS
Authors: Claus W. Jungeblut, Earl T. Engle
Journal: The Journal of Experimental Medicine (1934)

1. Adult rhesus monkeys possess frequently a greater resistance to experimental infection with poliomyelitis virus than young monkeys as indicated by the prolongation of the incubation period and the content of feeble neutralizing substances in the normal serum. 2. Virucidal substances can be demonstrated in the normal serum of subadult chimpanzees. 3. Immature monkeys prepared with glandular anterior pituitary hormones and anterior pituitary-like principles from the urine of pregnant women are protected only in exceptional instances against intracerebral infection with poliomyelitis virus. However, the serum of such prepared animals frequently acquires the property of inactivating the virus in vitro. 4. Active immunization with live poliomyelitis virus renders the immunized monkeys resistant to intracerebral infection in a higher percentage of the cases than does preparation with hormone. 5. The relative merits of non-specific enhancement of resistance and of specifically acquired immunity are discussed in their relation to the probable mechanism of resistance to poliomyelitis in man.
Prematurity and the Legacy of Intrauterine Stress
Authors: Julie R. Ingelfinger
Journal: New England Journal of Medicine (2007)

In 1960, a neonate weighing 1000 g had a 95% risk of death; today, a neonate with the same birth weight has a 95% chance of surviving. This progress in neonatology,1 including the advent and evolution of neonatal intensive care units (NICUs) and procedures that save premature infants, has led to markedly improved survival both for infants with very low birth weight (<1500 g) and for those with extremely low birth weight (<1000 g).What happens to these babies when they grow up? Although we know that prematurity may modify future lung function and cognitive abilities, much less is known . . .
Lung Perfusion Scintigram in a Patient With Tetralogy of Fallot and a Unidirectional Glenn Shunt A Case Report
Authors: MICHAEL S. McLEARY, MICHAEL H. WHOLEY, JOHN SCHWARTZ
Journal: Clinical Nuclear Medicine (1995)

A 30-year-old woman with a history of tetralogy of Fallot and a Glenn procedure had a lung scan because of suspicion of pulmonary embolism. Only the right lung showed perfusion. Because of the Glenn procedure, it would have been necessary to inject the Tc-99m MAA In a lower extremity vein.
Low-Density Lipoprotein Receptor–Related Protein Contributes to the Antiangiogenic Activity of Thrombospondin-2 in a Murine Glioma Model
Authors: Constance Y. Fears, J. Robert Grammer, Jerry E. Stewart, Douglas S. Annis, Deane F. Mosher, Paul Bornstein, Candece L. Gladson
Journal: Cancer Research (2005)

Abstract Host antiangiogenesis factors defend against tumor growth. The matricellular protein, thrombospondin-2 (TSP-2), has been shown to act as an antiangiogenesis factor in a carcinogen-induced model of skin cancer. Here, using an in vivo malignant glioma model in which the characteristics of the tumors formed after intracerebral implantation of GL261 mouse glioma cells are assessed, we found that tumor growth and microvessel density were significantly enhanced in tumors propagated in TSP-2−/− mice. Mechanistically, matrix metalloproteinase (MMP)-2 has been associated with neoangiogenesis and it has been proposed that the levels of available MMP-2 may be down-regulated by formation of a complex with TSP-2 that is internalized by low-density lipoprotein receptor–related protein 1 (LRP1). We found elevated expression of MMP-2 and MMP-9 in tumors propagated in TSP-2−/− mice, with a preferential localization in the microvasculature. In wild-type mice, MMP-2 was coexpressed with TSP-2 in the tumor microvasculature. In vitro, addition of recombinant (rec) TSP-2 to mouse brain microvessel endothelial cells reduced MMP-2 levels and invasion through mechanisms that could be inhibited by a competitive inhibitor of ligand binding to LRP1 or by siLRP1. Thus, the antiangiogenic activity of TSP-2 is capable of inhibiting the growth of gliomas in part by reducing the levels of MMP-2 in the tumor microvasculature. This mechanism is mediated by LRP1.
Abstract 3417: Increased anticancer effect of combining Wee1 (MK1775) and Chk1 (AZD7762) inhibitors in malignant melanoma cell lines.
Authors: Gry I. Magnussen, Vivi A. Florenes, Birgit Engesæter, Elisabeth Emilsen
Journal: Cancer Research (2013)

Abstract Malignant melanoma is one of the most increasing forms of cancer worldwide, in addition to being notoriously resistant to therapy. Despite recent advances, there are no curative treatments once the cancer has spread (stage IV); there is thus a precarious need to find new and better treatment alternatives. Unlike normal cells, the majority of cancer cells have a defective G1/S DNA-damage checkpoint and are therefore more dependent on the G2/M checkpoint when DNA damages arise. Central in regulating the latter checkpoint is Wee1, a kinase which may stop the cell cycle by adding a negative phosphorylation on CDK1. Wee1 is regulated by Chk1 which upon DNA damage can also inhibit the complimentary counterpart of Wee1; CDC25. In recent studies, Wee1 and Chk1 have additionally been indicated as key players in regulating DNA replication in S-phase. We have previously reported that increased Wee1 protein expression was associated with malignancy in melanoma tumour samples, and that siWee1 transfection led to reduced viability in melanoma cell lines. In the present study we have combined inhibitors of Wee1 (MK1775) and Chk1 (AZD7762) in a panel consisting of both metastatic melanoma- and normal cells, including a Plexxikon resistant melanoma cell line (MelJR post3.3). We found that the combination synergistically reduced the amount of viable cells in the melanoma cell lines (∼50-80% reduction), whilst only having very moderate effect (∼10% reduction) in the normal cells. Interestingly, the reduction in number of viable cells was found in both p53WT and p53Mut cell lines, indicating that the p53 status do not predict the response to such treatment. Furthermore, combinational treatment with the inhibitors caused increased cleavage of PARP and caspases, indicative of apoptosis, as compared to MK1775 or AZD7762 treatment alone. The combination also caused a marked increase in DNA double-strand breaks, as demonstrated by augmented levels of γ-H2AX (predominantly found in S-phase cells). In line with this, preliminary results from melanoma cells grown as spheroids, revealed the same tendency, with approximately 50% reduction in spheroid volume when combining the inhibitors. In vivo experiments using melanoma cells grown in SCID mice are currently ongoing. In conclusion, our results indicate a potential new role for inhibitors of Wee1 and Chk1 in treatment of malignant melanoma. Citation Format: Gry I. Magnussen, Vivi A. Florenes, Birgit Engesæter, Elisabeth Emilsen. Increased anticancer effect of combining Wee1 (MK1775) and Chk1 (AZD7762) inhibitors in malignant melanoma cell lines. [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 3417. doi:10.1158/1538-7445.AM2013-3417
Treatment of pulmonary aspergilloma with itraconazole.
Authors: J H Campbell, J H Winter, M D Richardson, G S Shankland, S W Banham
Journal: Thorax (1991)

In a 12 month open study of itraconazole in pulmonary aspergilloma nine patients received oral itraconazole 200 mg daily for six months followed by further itraconazole or observation for a further six months. There was no change in the serum IgG specific for Aspergillus fumigatus (mean (SE) change -4% (10%)) or symptoms of chronic cough and haemoptysis. In two of the three patients who continued treatment beyond six months symptoms and radiographic appearances improved and a temporary reduction in A fumigatus specific IgG occurred in one patient. Further experience of the effects of longer treatment are needed before oral itraconazole can be recommended for aspergilloma.
Peroxisome assembly factor–2, a putative ATPase cloned by functional complementation on a peroxisome–deficient mammalian cell mutant
Authors: Toshiro Tsukamoto, Satoshi Miura, Toshiki Nakai, Sadaki Yokota, Nobuyuki Shimozawa, Yasuyuki Suzuki, Tadao Orii, Yukio Fujiki, Fumie Sakai, Akemi Bogaki, Hiroaki Yasumo, Takashi Osumi
Journal: Nature Genetics (1995)
Treatment of Borderline Elevated Thyrotropin Levels
Authors: Susan S. Braithwaite, Justin B. Moore
Journal: JAMA Internal Medicine (2015)

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Health and the Rise of Civilization
Authors: Charles B. Arnold
Journal: JAMA (1990)

True or false? "Compared to prehistoric times, abundant evidence exists that mankind is healthier because of the rise of civilization." Difficult as it may seem, the correct answer is "false," according to author Mark Nathan Cohen. In this brief, scholarly treatise, he buttresses this provocative conclusion with abundant scientific support. The author, an anthropologist on the faculty of the State University of New York at Plattsburgh, has examined diverse findings from history, cultural and physical anthropology, epidemiology, nutrition, communicable disease, and other fields including physiology and medicine. Skepticism understandably could be expected to greet such a prodigious, interdisciplinary effort. In the preface, however, Professor Cohen squarely addresses such doubts with disarming candor (p vii): I cannot do justice to the full range of information available in any one field; nor can I fully appreciate, much less explain, all of the subtleties, debated by experts in each field, that cloud straightforward