tbuckley/cabot-search huggingface dataset:
Abstract 1988: Divergent control of Cav-1 expression in non-cancerous Li-Fraumeni Syndrome and human cancer cell lines.
Authors: Zaki A. Sherif, Ahmed S. Sultan
Journal: Cancer Research (2013)

Abstract Li-Fraumeni Syndrome (LFS) is primarily characterized by development of tumors exhibiting germ-line mutations in the p53 gene. Cell lines developed from patients of a LFS family have decreased p53 activity as evidenced by the absence of apoptosis upon etoposide treatment. To test our hypothesis that changes in gene expression beyond p53 per se are contributing to the development of tumors, we compared gene expression in non-cancerous skin fibroblasts of LFS-affected (p53 heterozygous) versus non-affected (p53 wild-type homozygous) family members. Expression analysis showed that several genes were differentially regulated in the p53 homozygous and heterozygous cell lines. We were particularly intrigued by the decreased expression (∼88%) of a putative tumor suppressor protein, caveolin-1 (Cav-1), in the p53-mutant cells. Decreased expression of Cav-1 was also seen in both p53-knockout and p21-knockout HTC116 cells suggesting that p53 controls Cav-1 expression through p21 and leading to the speculation that p53, Cav-1 and p21may be part of a positive auto-regulatory feedback loop. The direct relationship between p53 and Cav-1 was also tested with HeLa cells (containing inactive p53), which expressed a significantly lower Cav-1 protein. A panel of nonfunctional and p53-deficient colon and epithelial breast cancer cell lines showed undetectable expression of Cav-1 supporting the role of p53 in the control of Cav-1. However, in two aggressively metastasizing breast cancer cell lines, Cav-1 was strongly expressed suggesting a possible role in tumor metastasis. Thus, there is a divergent control of Cav-1 expression as evidenced in non-cancerous Li-Fraumeni Syndrome and some aggressive human cancer cell lines. Citation Format: Zaki A. Sherif, Ahmed S. Sultan. Divergent control of Cav-1 expression in non-cancerous Li-Fraumeni Syndrome and human cancer 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 1988. doi:10.1158/1538-7445.AM2013-1988
Sedating Drugs and Neuromuscular Blockade During Mechanical Ventilation
Authors: Gilles L. Fraser
Journal: JAMA (1992)

<h3>To the Editor.</h3> —One of the important points raised by Hansen-Flaschen et al<sup>1</sup>in their survey on the use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation is the wide range of costs associated with these therapies. I believe consideration should be given to sublingual lorazepam as a potential means of continuous sedation in intubated patients with nonfunctioning gastrointestinal tracts. The use of sublingual lorazepam has not been formally studied in the acute care setting. Support for investigation of the use of this drug should be encouraged by pharmacokinetic studies of commercially available oral formulations that indicate complete absorption with peak levels within 1 to 2 hours.<sup>2,3</sup>In addition, a double-blind, placebo-controlled trial has clearly demonstrated the clinical use of sublingual lorazepam as a sedative in the preoperative setting.<sup>4</sup>Lastly, the potential for substantial cost savings is impressive: one 2-mg tablet of lorazepam given
Research in Divisions of General Internal Medicine
Authors: GEORGE K. JOHNSON
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 February 1986Research in Divisions of General Internal MedicineGEORGE K. JOHNSON, M.D.GEORGE K. JOHNSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-2-279_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A recent article by Friedman and Pozen (1) has reported on a survey of the chairmen of departments of medicine about the status of their general internal medicine divisions. I am disappointed in the shortsighted views of the chairmen that the academic viability of general internal medicine divisions and their faculty is dependent on research productivity.The terms academic productivity, academic viability, and research capability are used interchangeably in the article. In the methods section, it was stated that the chairmen were asked questions in four areas: two were "factors affecting the academic productivity of...References1. FRIEDMANPOZEN RJ. The academic viability of general internal medicine: the views of department of medicine chairmen. Ann Intern Med. 1985;103:839-44. LinkGoogle Scholar2. PETERSDORF R. IS the establishment defensible? N Engl J Med. 1983;309:1053-7. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1986Volume 104, Issue 2Page: 279-280KeywordsAcademic medicine Issue Published: 1 February 1986 PDF DownloadLoading ...
Titin and Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease
Authors: Coen A. C. Ottenheijm, Leo M. A. Heunks, Theo Hafmans, Peter F. M. van der Ven, Caroline Benoist, Honghui Zhou, Siegfried Labeit, Henk L. Granzier, P. N. Richard Dekhuijzen
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Recently, we have shown that Ca2+-activated force generation in diaphragm single fibers is impaired in patients with mild to moderate chronic obstructive pulmonary disease (COPD). For optimal active-force generation, the passive elasticity provided by titin is indispensable.In the present study, we determined the passive-tension-length relations of single fibers of patients with mild to moderate COPD, hypothesizing that passive-elastic properties of diaphragm fibers are compromised.Passive-tension-length relations were determined in diaphragm fibers from patients with and without COPD (predicted mean FEV1, 76 and 102%, respectively). In diaphragm homogenates titin expression was studied at the protein level by gel electrophoresis and at the transcript level by using a novel titin exon microarray.Diaphragm fibers from patients with COPD generate less passive tension on stretch. Titin content in the diaphragm did not differ between patients with and without COPD. However, titin exon transcript studies revealed up-regulation of seven exons, which code for spring elements in the elastic segment rich in proline, glutamate, valine, and lysine. Immunofluorescence analysis indicated elevated protein expression of the up-regulated splice variant in the COPD diaphragm. Simulation studies on titin molecules including the amino acids encoded by the seven up-regulated exons predicted reduced passive-tension generation on molecule stretch.Passive-tension generation of diaphragm single fibers is reduced in patients with COPD. Our results suggest that alternative splicing of the titin gene, resulting in increased length of the elastic segment rich in proline, glutamate, valine, and lysine, is involved. Interestingly, these changes occur already in patients with mild to moderate COPD.
Detection of lymphocytotoxic antibodies in relatives of patients with type I diabetes.
Authors: J A Charlesworth, P Peake, L V Campbell, J Rumma, B A Pussell, N Howard, G J Elder
Journal: BMJ (1986)

Concentrations of lymphocytotoxic antibodies were measured in serum samples from 19 patients recently diagnosed as having type I diabetes and 43 healthy relatives (33 consanguineous and 10 non-consanguineous). The specificity of the reaction was tested at 15 degrees C and 37 degrees C against T lymphocytes and purified helper/inducer and cytotoxic/suppressor subsets. The concentrations of lymphocytotoxic antibodies in each of the three test groups were significantly higher than those in controls (type I patients, p less than 0.005; consanguineous relatives, p less than 0.001; and non-consanguineous relatives, p less than 0.002). The frequency of detection of the antibodies was also greater in each of the study groups (p less than 0.01, p less than 0.01, and p less than 0.05, respectively). Cytotoxicity affected both subsets at 15 degrees C but only cytotoxic/suppressor cells at 37 degrees C. The findings of lymphocytotoxic antibodies in healthy relatives of type I diabetics, irrespective of consanguinity, suggests that an environmental agent such as a virus is at least partially responsible for this lymphocytotoxic effect. Furthermore, the residual cytotoxic/suppressor cell killing at 37 degrees C could explain the defect of suppressor cells observed in these patients.
Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad-like lesions and recurrent mutation causing digital mutilation
Authors: N. Umegaki, H. Nakano, K. Tamai, Y. Mitsuhashi, E Akasaka, D. Sawamura, I. Katayama
Journal: British Journal of Dermatology (2011)

Journal Article Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad‐like lesions and recurrent mutation causing digital mutilation Get access N. Umegaki, N. Umegaki Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar H. Nakano, H. Nakano Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu‐cho, Hirosaki 036‐8562, Japan Hajime Nakano. E‐mail: hnakano@cc.hirosaki‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Tamai, K. Tamai Stem Cell Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Mitsuhashi, Y. Mitsuhashi Department of Dermatology, Tokyo Medical University, Tokyo, Japan Search for other works by this author on: Oxford Academic Google Scholar E Akasaka, E Akasaka Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu‐cho, Hirosaki 036‐8562, Japan Search for other works by this author on: Oxford Academic Google Scholar D. Sawamura, D. Sawamura Department of Dermatology, Hirosaki University Graduate School of Medicine, 5 Zaifu‐cho, Hirosaki 036‐8562, Japan Search for other works by this author on: Oxford Academic Google Scholar I. Katayama I. Katayama Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 199–201, https://doi.org/10.1111/j.1365-2133.2011.10317.x Published: 01 July 2011
Abstract 3533: Clinical impact of NF-KB activation in diffuse large B cell lymphoma.
Authors: Lina Odqvist, Santiago Montes-Moreno, Margarita Sánchez-Beato, Lydia Sánchez-Verde, Manuela Mollejo, Ken H. Young, Manuel F. Fresno, Francisco Mazorra, Carmen Ruíz-Marcellán, Miguel A. Piris
Journal: Cancer Research (2013)

Abstract Deregulated nuclear factor KB (NF-KB) activity has been associated with a number of lymphoproliferative diseases, including diffuse large B cell lymphoma (DLBCL), but the importance and consequence of this activation are still not fully understood. In this study, we describe the extent of NF-KB activation in a range of human lymphoma types and observe a frequent concurrent activation of both classical and alternative pathways in DLBCL. The activation of the classical and alternative NF-KB pathways, was present in 34.8% and 29.3% of DLBCL cases respectively, as assessed by nuclear expression of p50 (classical pathway) and p52 (alternative pathway) by immunohistochemistry in a series of 167 samples. Activation of NF-KB was observed in both germinal centre B-cell like (GC) and activated B-cell like (ABC) subtypes, although with a predominance of classical NF-KB in the ABC subtype (41,8% positive cases versus 21,2% in the GC subtype). In our cohort of samples from 167 R-CHOP treated DLBCL patients, excluding cases positive for Epstein-Barr virus, nuclear expression of NF-KB was significantly associated with a superior overall survival (Log Rank p&amp;lt;0.05), as compared to those without nuclear NF-KB. The 3-year overall survival rate in the NF-KB positive group was 83.6% compared to 68.0% in the NF-KB negative group. While p50 expression alone did not give rise to any significant differences in the survival curves, p52 expression did associate significantly with better clinical outcome (p=0.032). Thus, alternative NF-KB activation is frequently present in DLBCL tumors, is not associated with the ABC subtype, and is characterized by an enhanced overall survival. Citation Format: Lina Odqvist, Santiago Montes-Moreno, Margarita Sánchez-Beato, Lydia Sánchez-Verde, Manuela Mollejo, Ken H. Young, Manuel F. Fresno, Francisco Mazorra, Carmen Ruíz-Marcellán, Miguel A. Piris. Clinical impact of NF-KB activation in diffuse large B cell lymphoma. [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 3533. doi:10.1158/1538-7445.AM2013-3533
Exercise-Associated Urinary Incontinence
Authors: John M. Thorp
Journal: JAMA (1991)

<h3>To the Editor.—</h3> The patient with exercise-associated urinary incontinence presented in the Questions and Answers section of the January 23, 1991, issue of<i>JAMA</i>could well have another source for her perineal wetness than that mentioned by the consultants.<sup>1</sup>Her symptomless onset of perineal wetness occurring solely in the periovulatory portion of her cycle might well be cervical mucus under the influence of estrogen. My anecdotal experience in caring for a number of women who use contraception with ovulation-prediction techniques supports such a diagnosis, as many of these patients report copious passage of mucus with exercise. Interestingly enough, this seems to be a complaint limited to parous women and has its onset after the cessation of lactation when ovulation resumes. My hypothesis could be easily tested by having the patient wear a perineal pad in the periovulatory period while exercising. Close inspection would allow differentiation between mucus and urine
AB0383 Measuring partial and complete recovery in active organ systems of lupus patients on standard of care treatment
Authors: Z. Touma, M. B. Urowitz, D. Ibanez, S. Taghavi-Zadeh, D. D. Gladman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SLEDAI-2K Responder Index-50 (S2K RI-50) is a novel index that measures partial recovery (PR), ≥50% improvement in active descriptors. <h3>Objectives</h3> To determine: 1) PR and complete recovery (CR) in active systems on standard of care (SOC) treatment and 2) the benefit of measuring ≥50% improvement in active descriptors with S2K RI-50. <h3>Methods</h3> Patients seen from February 2009 to May 2012 with at least one active system were analysed. We excluded patients with CNS or with nephrotic range proteinuria lupus nephritis. CR was measured with SLEDAI-2K and PR with S2K RI-50. <h3>Results</h3> 548 patients (90% F) with at least one active SLEDAI-2K system were analyzed. Age at lupus diagnosis was 29.2 ± 12.3 years and disease duration at study inclusion was 15.2 ± 11.0 years. Among the 8 system studied at baseline, the most commonly represented systems were: immunology, renal, mucocutaneous and musculoskeletal. In 117 patients with mucocutaneous involvement, CR by SLEDAI-2K was achieved by 68 patients at 6 months, by 95 patients at 12 months and 106 patients at 2 years. PR and CR by S2K RI-50 were identified in 83 patients at 6 months, 105 patients at 12 months and 113 patients at 2 years. The number of patients who achieved PR and CR by S2K RI-50 was greater than the number of patients who achieved CR by SLEDAI-2K in all studied systems (Table 1). The total possible score for the mucocutaneous system by SLEDAI-2K is 6. At baseline visit the total score for the mucocutaneous system was 2.56±1.01. At 6 months the score decreased to 1.02±1.51, at 12 months to 0.47±1.07 and to 0.27±0.91 at 2 years by SLEDAI-2K. At 6 months the score decreased to 0.87±1.35, 12 months to 0.40±0.95 and at 2 years to 0.20±0.67. The decrease of S2K RI-50 scores was greater than the decrease of SLEDAI-2K scores in all active systems. <h3>Conclusions</h3> With SOC treatment, patients improve progressively over a 2 year period. The use of S2K RI-50 allows the capture of an additional number of patients with ≥50% improvement in active systems not discerned by SLEDAI-2K. S2K RI-50 will allow for an earlier signal of efficacy with new agents in therapeutic trials. <h3>Disclosure of Interest</h3> None Declared
MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression
Authors: Akemi Takata, Motoyuki Otsuka, Takeshi Yoshikawa, Takahiro Kishikawa, Yohko Hikiba, Shuntaro Obi, Tadashi Goto, Young Jun Kang, Shin Maeda, Haruhiko Yoshida, Masao Omata, Hiroshi Asahara, Kazuhiko Koike
Journal: Hepatology (2012)

MicroRNAs (miRNAs) are small RNAs that regulate the expression of specific target genes. While deregulated miRNA expression levels have been detected in many tumors, whether miRNA functional impairment is also involved in carcinogenesis remains unknown. We investigated whether deregulation of miRNA machinery components and subsequent functional impairment of miRNAs are involved in hepatocarcinogenesis. Among miRNA-containing ribonucleoprotein complex components, reduced expression of DDX20 was frequently observed in human hepatocellular carcinomas, in which enhanced nuclear factor-κB (NF-κB) activity is believed to be closely linked to carcinogenesis. Because DDX20 normally suppresses NF-κB activity by preferentially regulating the function of the NF-κB-suppressing miRNA-140, we hypothesized that impairment of miRNA-140 function may be involved in hepatocarcinogenesis. DNA methyltransferase 1 (Dnmt1) was identified as a direct target of miRNA-140, and increased Dnmt1 expression in DDX20-deficient cells hypermethylated the promoters of metallothionein genes, resulting in decreased metallothionein expression leading to enhanced NF-κB activity. MiRNA-140-knockout mice were prone to hepatocarcinogenesis and had a phenotype similar to that of DDX20 deficiency, suggesting that miRNA-140 plays a central role in DDX20 deficiency-related pathogenesis.These results indicate that miRNA-140 acts as a liver tumor suppressor, and that impairment of miRNA-140 function due to a deficiency of DDX20, a miRNA machinery component, could lead to hepatocarcinogenesis.
Otitis Externa Granulosa
Authors: N. A. Punt
Journal: BMJ (1949)

BDICA JOUR 989 remission following dietetic and /or parenteral liver therapy occurred in 69.4% of these cases and definite relapse in 16.1 %, nearly all of whom first relapsed during transit to England.A brief review of the effective factors of treatment is given and the action of parenteral liver therapy analysed.
Protein Tyrosine Phosphatase Type-1 (PTPN1) Is Frequently Mutated In Primary Mediastinal B Cell Lymphoma and Hodgkin Lymphoma
Authors: Jay Gunawardana, Fong Chun Chan, Adele Telenius, Bruce W. Woolcock, Robert Kridel, King L. Tan, Susana Ben Neriah, Raymond S. Lim, Sanja Rogic, Merrill Boyle, Chrystelle Guiter, Karen Leroy, Corinne Haioun, Lisa M. Rimsza, Philippe Gaulard, Kerry J. Savage, Joseph M. Connors, Marco A. Marra, Sohrab P. Shah, Randy D. Gascoyne, Christian Steidl
Journal: Blood (2013)
A History of Biochemistry
Authors: Lester S. King
Journal: JAMA (1973)

To cover the vast range of modern biochemistry, Dr. Marcel Florkin and Dr. Elmer Stotz have edited a massive series entitled "Comprehensive Biochemistry," that embraces 29 volumes. Now, as a capstone, the editors are bringing out a historical survey, written by Dr. Florkin, that will eventually run to four more volumes, of which this book is the first. Dr. Florkin is not only an eminent biochemist but also a noted medical historian, and a past president of the International Academy of the History of Medicine. His original intention was to limit the historical presentation to the modern period, starting in 1897. But to make this meaningful he had to present the earlier doctrines. History of more modern developments will, presumably, form the subject of the second, third, and fourth volumes, still to be published. In the present work Florkin divides the early history into two parts. The first discusses the
Costs, Charges, Conscience, and Control (Lost)
Authors: George D. Lundberg
Journal: JAMA (1983)

Have you seen the most recent report on the rate of inflation overall and by its several components?<sup>1</sup> The Consumer Price Index rose at an annualized rate of 4.1% during August 1983. By comparable calculations, physician services rose by only 3.4%, but medical care rose by 8.0%. This increase was produced primarily by the hospital room component, which climbed at an annualized rate of 17.8%. Good grief!! Can't we do better than that? This 17.8% figure doesn't even include many other hospital budget elements wherein creative hospital directors and accountants have traditionally "laid it off on the ancillaries." Is the hospital industry (wherein physicians certainly influence costs) intentionally riding "hell bent for leather" toward destruction of self-control or is this simply ignorance? From many years of working with large bureaucratic budgets, I am tempted to lay part of the blame for this extraordinary spurt on what was the then-impending
Lime versus Lyme Disease
Authors: Lorraine Tosiello
Journal: Annals of Internal Medicine (1991)

Letters15 July 1991Lime versus Lyme DiseaseLorraine Tosiello, MDLorraine Tosiello, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-2-157 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: No doubt you will receive many letters in response (or reaction) to the facitious essay on "Lime disease" by Dr. Lettau (1); however, I feel compelled to add my voice.The tongue-in-cheek attitude expressed in the essay reflects the skepticism that so many physicians brandish when our medical knowledge falls short of an elusive diagnosis. Unfortunately, this attitude does little to assuage the pain of our patients who suffer from undiagnosed fatigue symptoms. I am not so certain that the current state of our knowledge can distinguish atypical presentations of Lyme disease or the other fatigue syndromes...Reference1. Lettau L. From the Centers for Fatigue Control (CFC) Weekly Report. Lime disease—United States. Ann Intern Med. 1991 ;114:602. LinkGoogle Scholar1. Sigal L. Summary of the first 100 patients seen at a Lyme disease referral center. Am J Med. 1990;88:577-81. CrossrefMedlineGoogle Scholar2. HedbergOsterholm CM. Serologic tests for antibody to Borrelia burgdorferi. Another Pandora's box for medicine? Arch Intern Med. 1990;150:732-3. CrossrefMedlineGoogle Scholar3. Steere A. Lyme disease. N Engl J Med. 1989;321:586-96. CrossrefMedlineGoogle Scholar4. Lettau L. Antibiotics 1999. Ann Intern Med. 1989;110:850. LinkGoogle Scholar5. Weinberg R. The once and future physician. Ann Intern Med. 1989;110:753. LinkGoogle Scholar1. Lettau L. From the Centers for Fatigue Control (CFC) Weekly Report. Lime disease—United States. Ann Intern Med. 1991;114:602. LinkGoogle Scholar1. Lettau L. From the Centers for Fatigue Control (CFC) Weekly Report. Lime Disease—United States. Ann Intern Med. 1991;114:602. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 123 Woodland Avenue Westfield, NJ 07090 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDiagnosing Lyme DiseaseJames R. Johnson, MDThe neuropsychiatric manifestations of Lyme borreliosis 15 July 1991Volume 115, Issue 2Page: 157-158KeywordsFallsFatigueLyme disease Issue Published: 15 July 1991 PDF DownloadLoading ...