tbuckley/cabot-search huggingface dataset:
Abstract P1-08-36: Neoadjuvant trial of bevacizumab (B) and trastuzumab (T) in combination with weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast cancer: A phase II trial (AVANTHER). Analysis of biomarkers
Authors: M Fernández, N Martinez, I Calvo, E Garcia, L Ugidos, M Herrero, Y Quijano, H Durán, M Garcia, A Suarez, F López-Rios, D Perez, S Perea, M Hidalgo, L Garcia-Estevez
Journal: Cancer Research (2013)

Abstract Background: AVANTHER is a phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination. The primary endpoint was pathological complete response (pCR), defined as the absence of invasive disease at the time of histological study. Tissue samples were collected at baseline and the relationship between the expression of PTEN, PI3KCA, TOPO 2a, VEGF, activation of insulin growth factor 1-receptor (IGF1R) and pCR was assessed. Methods: Patients (pts) with centrally-confirmed HER2–positive (IHC 3+ or FISH amplified) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles). Tumor samples were evaluated for the expression of PTEN and TOPO 2α by fluorescent in situ hybridization (FISH), IGF-1R, VEGF, and EGFR using standard immunohistochemistry (IHC). Status of PI3KCA was determined using Fluidigm-based real-time PCR. Results: A total of 44 pts were enrolled. Median tumor size: 3.9 cm. Nine (21%) pts had stage IIA; 19 (45%) stage IIB; 10 (24%) stage IIIA and 4 (10%) stage IIIB. Twenty-nine (69%) pts had estrogen positive receptors. PCR achieved was 42.9%. PTEN expression was normal in all pCR group and 1 patient (pt) (3.8%) had a PTEN deletion in group with no pCR. PI3KCA was mutated in 3pts (16.7%) (1pt E542k and 2 pts H1047r) in the pCR group and 4 pts (15.4%) (1pt E545k, 1pt G1049r and 2 pts H1047r) in the no pCR. Topo 2α was amplified in 8 pts in both groups. The expression of IGFR 1 was negative in 44.4% in the pCR group and 15.4% in patients with no pCR (p = 0.04). VEGF was positive in 7pts (39%) in pCR group and 10pts (38.5%) in no pCR. Conclusions: Our results are in agreement with some prior studies that show that expression of IGFR could be correlated with trastuzumab resistance. Therefore, these findings raise a hypothesis to be validated in prospective studies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-36.
Decreased cardiac L-type Ca2+ channel activity induces hypertrophy and heart failure in mice
Authors: Sanjeewa A. Goonasekera, Karin Hammer, Mannix Auger-Messier, Ilona Bodi, Xiongwen Chen, Hongyu Zhang, Steven Reiken, John W. Elrod, Robert N. Correll, Allen J. York, Michelle A. Sargent, Franz Hofmann, Sven Moosmang, Andrew R. Marks, Steven R. Houser, Donald M. Bers, Jeffery D. Molkentin
Journal: Journal of Clinical Investigation (2011)

Antagonists of L-type Ca²⁺ channels (LTCCs) have been used to treat human cardiovascular diseases for decades. However, these inhibitors can have untoward effects in patients with heart failure, and their overall therapeutic profile remains nebulous given differential effects in the vasculature when compared with those in cardiomyocytes. To investigate this issue, we examined mice heterozygous for the gene encoding the pore-forming subunit of LTCC (calcium channel, voltage-dependent, L type, α1C subunit [Cacna1c mice; referred to herein as α1C⁻/⁺ mice]) and mice in which this gene was loxP targeted to achieve graded heart-specific gene deletion (termed herein α1C-loxP mice). Adult cardiomyocytes from the hearts of α1C⁻/⁺ mice at 10 weeks of age showed a decrease in LTCC current and a modest decrease in cardiac function, which we initially hypothesized would be cardioprotective. However, α1C⁻/⁺ mice subjected to pressure overload stimulation, isoproterenol infusion, and swimming showed greater cardiac hypertrophy, greater reductions in ventricular performance, and greater ventricular dilation than α1C⁺/⁺ controls. The same detrimental effects were observed in α1C-loxP animals with a cardiomyocyte-specific deletion of one allele. More severe reductions in α1C protein levels with combinatorial deleted alleles produced spontaneous cardiac hypertrophy before 3 months of age, with early adulthood lethality. Mechanistically, our data suggest that a reduction in LTCC current leads to neuroendocrine stress, with sensitized and leaky sarcoplasmic reticulum Ca²⁺ release as a compensatory mechanism to preserve contractility. This state results in calcineurin/nuclear factor of activated T cells signaling that promotes hypertrophy and disease.
THE TREATMENT OF ACNE BY VACCINES
Authors: MALCOLM MORRIS, ERNEST DORE
Journal: British Journal of Dermatology (1911)

Journal Article THE TREATMENT OF ACNE BY VACCINES Get access MALCOLM MORRIS, K.C.V.O. SIR, MALCOLM MORRIS, K.C.V.O. SIR Search for other works by this author on: Oxford Academic Google Scholar ERNEST DORE, M.D., M.R.C.P. ERNEST DORE, M.D., M.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 23, Issue 10, 1 October 1911, Pages 311–322, https://doi.org/10.1111/j.1365-2133.1911.tb16658.x Published: 01 October 1911
Immunofluorescent microscopic investigation of the distal arrector pili: A demonstration of the spatial relationship between ?5?1 integrin and fibronectin
Authors: Missy M. Cliftona,b, Jerri K. Mendelsona, Bruce Mendelsone, Donna Montaguec, Charleata Carterd, Bruce R. Smollera,b, Thomas D. Horn
Journal: Journal of the American Academy of Dermatology (2000)
NEUROPSYCHIATRIC ASPECTS OF CHOREA IN CHILDREN
Authors: FRANKLIN G. EBAUGH
Journal: JAMA (1926)

Although numerous articles have been written on the subject of chorea in children, the important and often serious neuropsychiatric aspects of this disease have not been adequately emphasized. When we describe the sudden, irregular, purposeless, incoordinate movements of chorea we should realize that the mental disturbances are apt to be of an emotional nature of similarly irregular type. These emotional disturbances may incapacitate the child and assume an equal or greater significance than the well known motor symptoms of the disease. The personality of the child may suffer after he has passed through a period of lack of motor control, and this may be shown by various defects of adjustment, including a relationship to juvenile delinquency. The interference with school progress during the receptive period of the child may assume great importance in the later adaptation of the child. The material used for this report includes thirty-two school children referred
Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase
Authors: Kittipong Maneechotesuwan, Wuttichai Ekjiratrakul, Kanda Kasetsinsombat, Adisak Wongkajornsilp, Peter J. Barnes
Journal: Journal of Allergy and Clinical Immunology (2010)
Endoscopic Image Manipulation: State of the Art
Authors: M. A. Fujino, T. Kawai, A. Morozumi, Y. Yamamoto, M. Ikeda, H. Suzuki
Journal: Endoscopy (1992)

Fundamental techniques and commonly employed algorithms for image manipulation of endoscopic images were reviewed, but only in a few instances was any novel information obtained. New software was recently developed for medium-frequency band enhancement: From the correlation distribution of image data in the RGB color space (distribution 1), only those data components depicting the fine structure patterns were extracted. The correlation distribution of the latter components was subsequently studied in the same space (distribution 2); the original image data were so processed that distribution 1 would be enhanced along the axis of greatest variation seen in distribution 2. This algorithm of image processing was successful in detecting minute surface structures of the mucosa hidden by the overlying mucus in the original images. It seems to be the first successful algorithm of image processing that obtained specific effects of enhancement without simultaneous noise enhancement.
Crashes and Violations among Older Drivers
Authors: Richard A. Marottoli
Journal: Annals of Internal Medicine (1995)

Letters1 June 1995Crashes and Violations among Older DriversRichard A. Marottoli, Leo M. Cooney, and Mary E. TinettiRichard A. MarottoliSearch for more papers by this author, Leo M. CooneySearch for more papers by this author, and Mary E. TinettiSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-11-199506010-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:When advising a driver of any age, physicians should consider any medical condition that may affect alertness and consciousness while driving. Because relatively few persons in our sample had any one medical condition, we did not feel it was appropriate to draw conclusions about the effect of those medical conditions on driving ability. Therefore, we recommended that such instruments, once fully developed and tested, “be used to supplement existing recommendations about specific medical conditions and driving.” Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1995Volume 122, Issue 11Page: 885KeywordsConsciousnessMedical conditions Issue Published: 1 June 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Heterosexual AIDS: Myth or Epidemic?-Reply
Authors: Renslow Sherer
Journal: JAMA (1990)

<h3>In Reply.—</h3> Here in the United States there was a 36% increase in heterosexually transmitted AIDS from 1988 to 1989; this ranks with perinatally transmitted HIV (38% increase) as the fastest growing categories of transmission.<sup>1</sup>Furthermore, 25% of women with AIDS in the United States acquired the disease heterosexually; for these individuals, heterosexual AIDS is no myth. Data on trends in AIDS give us epidemiologic information that is 10 years old; when available, HIV infection data are more indicative of current trends. It certainly is true that some of the data on prevalence of HIV among heterosexuals at risk in low-incidence areas in the United States are reassuring; for example, heterosexuals attending sexually transmitted disease clinics in rural Illinois have a prevalence of 0.54%.<sup>2</sup>Nevertheless, the military recently found for the first time near-equivalent seroprevalence rates among male and female recruits (0.8 per 1000 vs 0.7 per 1000,
Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus
Authors: Eike Steinmann, Thomas Whitfield, Stephanie Kallis, Raymond A. Dwek, Nicole Zitzmann, Thomas Pietschmann, Ralf Bartenschlager
Journal: Hepatology (2007)

Current therapy of chronic hepatitis C is based on the combination of pegylated interferon-α and ribavirin. In spite of 50% sustained virological response, therapy is still limited by unsatisfying success rates with genotype 1 infections and adverse side effects. One attempt to increase success rates is triple combination therapy of interferon and ribavirin with amantadine, a drug assumed to interfere with HCV p7 ion channel function. However, results from clinical trials indicate limited efficacy and the antiviral activity is unclear. In contrast, NS3 protease inhibitors have shown potent antiviral effects in clinical trials but rapid selection for drug resistance may limit their benefit. Targeting cellular factors required for HCV is therefore an attractive alternative. In this study, employing a system for production of infectious HCV particles in cell culture, we determined the antiviral effects of amantadine and iminosugar derivatives; the second of which primarily target host cell glucosidases required for folding and maturation of HCV envelope glycoproteins. We found that across a spectrum of HCV isolates and genotypes, amantadine affected neither RNA replication nor the release or infectivity of HCV particles. In agreement, p7 ion channel activity was not affected by amantadine, demonstrating that amantadine is not an HCV-selective antiviral. In contrast, a dose-dependent reduction of virus titers was achieved with iminosugars. Furthermore, HCV was rapidly eliminated from cell culture upon passage in the presence of a long alkyl chain deoxynojirimycin (DNJ). Conclusion: Iminosugar derivatives are potential drugs for treatment of HCV infections. (HEPATOLOGY 2007.)
Binding and suppressive activity of human recombinant ferritins on erythroid cells
Authors: Silvia Fargion, Maria Domenica Cappellini, Anna Ludovica Fracanzani, Tullia Maria de Feo, Sonia Levi, Paolo Arosio, Gemino Fiorelli
Journal: American Journal of Hematology (1992)

Abstract We studied the relation between ferritin cellular binding and suppressive activity of recombinant H‐ and L‐ferritin on human erythroid cells at different proliferation/differentiation phases. L‐ferritin failed to show any suppressive activity or detectable binding to erythroblasts at any stage of maturation. In contrast, H‐ferritin demonstrated binding to erythroblasts derived from peripheral BFU‐E cells which increased steadily between 7‐14 days of culture up to 15,000 molecules per cell. Reticulocytes and erythrocytes failed to bind either L‐ or H‐ferritin. H‐ferritin suppressed BFU‐E colony formation and reduced K562 cell proliferation at nanomolar concentrations. This suggests that the expression of H‐ferritin binding sites is modulated by cellular proliferation and differentiation, that cells expressing H‐ferritin binding sites are sensitive to ferritin suppressive activity and that a causal relation exists between ferritin cellular binding and suppressive activity.
Narrative Review: BRAF Opens the Door for Therapeutic Advances in Melanoma
Authors: Keith T. Flaherty
Journal: Annals of Internal Medicine (2010)

Patients with metastatic melanoma have a poor prognosis and limited treatment options. In about one half of analyzed patients with metastatic melanoma, a mutated signal transduction molecule has been identified: v-raf murine sarcoma viral oncogene homolog B1 (BRAF). This molecule is part of an intracellular signaling cascade and may play a role in many different types of cancer. This article provides an overview of the current treatment options for metastatic melanoma and describes the pathophysiology underlying the development of therapies based on inhibition of BRAF. It summarizes findings of phase 1 and phase 2 studies of BRAF inhibitor therapy primarily in patients with metastatic melanoma, who have shown objective response rates of 70% to 80%. However, initial responses have not been sustained, with a median time to relapse of approximately 9 months. Clinicians should be aware of phase 3 trials of these agents and trials combining these therapies with other novel therapies because, at a minimum, BRAF inhibitors seem to be valuable as palliative therapy for metastatic melanoma.
Regional Myocardial Perfusion Rates in Patients with Coronary Artery Disease
Authors: Paul J. Cannon, Ralph B. Dell, Edward M. Dwyer
Journal: Journal of Clinical Investigation (1972)

Regional myocardial perfusion rates were estimated from the myocardial washout of (133)Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of (133)Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula. The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%. In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels. In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary arteriograms. In the patients with abnormal left coronary arteriograms, the average coefficient of variation of local left ventricular perfusion rates was significantly increased (24.8%). The studies provide evidence that coronary artery disease is associated with increased heterogeneity of local myocardial perfusion rates. They indicate that radiographically significant vascular pathology of the right or left coronary artery may be associated with significant reductions of myocardial capillary perfusion in the region supplied by the diseased vessel.
Light and dark in life and death
Authors: J. Roberts
Journal: BMJ (1996)

Athletic prowess represents the rugged, individualistic, can-do attitude that Americans perceive in themselves. Over the past two weeks the sports metaphor has been particularly poignant, showing the best of America and the saddest. Not surprisingly, the catalyst has been AIDS.

On 6 February, a few minutes into a basketball game between the Los Angeles Lakers and the Golden State Warriors, a man perceived to be dying of HIV walked on to the court and received a wild ovation from the 17000 fans and three million more watching on television.

In 1991 Magic Johnson, one of the most talented athletes in basketball, retired because he had tested positive for HIV and because of fears that he might infect other players. But this month Johnson stepped on to the court, supported by fellow players, and …
Do Economic Slumps Increase Illness?
Authors: Max Bader
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In "Do Economic Slumps Increase Illness?" (242:1241, 1979), a correlation between ischemic heart disease and economic conditions is suggested. Between 1968 and the end of 1971, the Seattle area's largest employer reduced its work force from more than 100,000 to fewer than 40,000 employees, costing the community a huge proportion of its basic industry jobs. Few communities since the Depression have experienced such severe unemployment so quickly, and many employees with 15 to 20 years' seniority were stunned to find themselves laid off and without any job prospects. Rahe et al<sup>1</sup>and Petrich and Holmes<sup>2</sup>have shown that life crises such as loss of employment are associated with illness development, yet it is surprising how little (if any) effect the Seattle-area recession had on heart disease mortality in men aged 55 to 64 years (Table). Also, in contrast to the Australia experience, coronary heart disease
Reply to Peter E.P. Petros’ Letter to the Editor re: Ruth C. Lovegrove Jones, Qiyu Peng, Maria Stokes, Victor F. Humphrey, Christopher Payne, Christos E. Constantinou. Mechanisms of Pelvic Floor Muscle Function and the Effect on the Urethra During a Cough. Eur Urol 2010;57:1101–10
Authors: Ruth Lovegrove Jones, Qiyu Peng, Maria Stokes, Victor Humphrey, Chris Payne, Christos Constantinou
Journal: European Urology (2010)
The melanoma epidemic: reality and artefact
Authors: J. L Rees
Journal: BMJ (1996)

Skin watchers have their own equivalent of the Heisenberg uncertainty principle. Just as you can't know exactly both the momentum and the position of a single electron, once you excise a pigmented lesion and know its histology you forfeit the chance of knowing what would have happened if you had left it in situ; progression, metastasis, or even involution are all possible. Removal of pigmented lesions is now one of the commonest surgical procedures and has radically changed the pattern of referrals to dermatologists. Epidemiological studies show a dramatic increase in histologically confirmed melanomas1 and raise the important questions of whether the increase is real or a diagnostic artefact and whether we should reconsider the relation between sun exposure and melanoma.

The incidence of melanoma has increased by 3-7% per year from the mid-1950s to the early 1980s.1 2 3 These changes have been seen in both sexes and in a large number of different caucasian communities in both the …
Statement by the International Committee of Medical Journal Editors on Duplicate or Redundant Publication
Authors: George D. Lundberg
Journal: JAMA (1993)

The International Committee of MedicalJournal Editors (also known as the Vancouver Group) was founded in 1978 and currently comprises editors of 11 medical journals in six countries and two consultants.<sup>1</sup>It publishes statements about how authors and editors of medical journals should behave.<sup>2</sup>These statements are binding on no one, but are followed by more than 300 journals worldwide and represent all continents. Because many authors are confused about replicate submissions<sup>3,4</sup>and because problems in this area are commonplace,<sup>5-7</sup>the committee expanded, clarified, and strengthened its original statement at a meeting in Chicago on September<sup>8</sup>, 1993. <h3>DUPLICATE OR REDUNDANT PUBLICATION</h3> Most journals, especially primary source periodicals, do not wish to receive papers on work that has already been reported in a published article or is contained in another paper that has been submitted or accepted for publication elsewhere in print or in electronic media. This
Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development.
Authors: J W Bigbee, K V Sharma, J J Gupta, J L Dupree
Journal: Environmental Health Perspectives (1999)

Acetylcholinesterase (AChE) is the enzyme that hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses and neuromuscular junctions. However, results from our laboratory and others indicate that AChE has an extrasynaptic, noncholinergic role during neural development. This article is a review of our findings demonstrating the morphogenic role of AChE, using a neuronal cell culture model. We also discuss how these data suggest that AChE has a cell adhesive function during neural development. These results could have additional significance as AChE is the target enzyme of agricultural organophosphate and carbamate pesticides as well as the commonly used household organophosphate chlorpyrifos (Dursban). Prenatal exposure to these agents could have adverse effects on neural development by interfering with the morphogenic function of AChE.