tbuckley/cabot-search huggingface dataset:
P1-07-14: Quantum Dot-Labelled Antibodies To Assess HER2 Expression in Breast Cancer.
Authors: S Zona, E Blackburn, AS Hojjatoleslami, IR Brown, WJ Gullick
Journal: Cancer Research (2011)

Abstract Background: The Human Epidermal Growth Factor Receptor 2 (HER2) is overexpressed in 18–20% of breast cancers. Herceptin is an effective drug for the treatment of breast cancers expressing high levels of HER2. It is well known that there is a correlation between levels of HER2 expression and response to Herceptin. However a proportion of patients selected for Herceptin treatment do not respond to the drug. The accuracy of the assessment of HER2 levels in breast cancer is therefore important to predict patients’ response to Herceptin therapy. The current techniques in clinical use for the assessment of HER2 are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); however both IHC and FISH have several limitations which may result in patient misclassification. A more accurate technique, which can quantify HER2 levels more precisely, could help to improve clinical diagnosis, prediction of prognosis and allow more accurate select individual patients for particular drug therapies. Materials and Methods: We employed QDs labelled antibodies, laser scanning confocal microscopy and image segmentation techniques to quantify HER2 expression in cases of formalin fixed paraffin embedded breast cancers. Quantum dots (QDs) are a new class of fluorochromes made of semiconductor nanocrystal which have several useful properties for quantitative image analysis. In order to validate the system we used a breast cancer HER2−IHC control tissue array with negative, low, moderate and strong expressing cases, and a tissue microarray containing 60 samples of formalin fixed paraffin embedded breast cancer sections, previously examined by IHC and scored semiquantitatively (0-3+). We then applied this system to quantify HER2 expression a tissue microarray containing 150 primary breast cancers scored as 3+ by IHC from patients treated with Herceptin. Results: We first demonstrated that the QD system could reliably detect HER2 expression in IHC 3+ cases. A comparison of immunofluorescent staining with conventional immunohistochemistry showed that QDs give more linear and scalable measurements of receptor levels. We also quantified HER2 within a set of 150 breast cancers scored as 3+ by IHC, and we found that HER2 is expressed at very different levels, ranging over fifty fold between individual (IHC3+) cases. We currently are evaluating the correlation between HER2 receptor levels, measured by QDs, and patient's response to Herceptin. Conclusion: QDs and image analysis can produce a more precise measurement of HER2 levels of expression than IHC. This should help to improve clinical diagnosis, prognosis, identify specific treatments for individual patients and reduce costs associated with Herceptin treatment. This technology may be applied to study other members of the EGF family in breast cancers or more widely as a quantitative measurement of biomarkers in tumours. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-14.
GATA2 is critical for the maintenance of cellular identity in differentiated mast cells derived from mouse bone marrow
Authors: Shin’ya Ohmori, Takashi Moriguchi, Yuki Noguchi, Muneharu Ikeda, Kota Kobayashi, Nazuki Tomaru, Yasushi Ishijima, Osamu Ohneda, Masayuki Yamamoto, Kinuko Ohneda
Journal: Blood (2015)
Blood pressure homeostasis is maintained by a P311–TGF-β axis
Authors: Kameswara Rao Badri, Ming Yue, Oscar A. Carretero, Sree Latha Aramgam, Jun Cao, Stephen Sharkady, Gene H. Kim, Gregory A. Taylor, Kenneth L. Byron, Lucia Schuger
Journal: Journal of Clinical Investigation (2013)

P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311-/-) mice display learning and memory defects, but alterations in their vasculature have not been previously described. Here we report that P311-/- mice are markedly hypotensive with accompanying defects in vascular tone and VSMC contractility. Functional abnormalities in P311-/- mice resulted from decreased total and active levels of TGF-β1, TGF-β2, and TGF-β3 that arise as a specific consequence of decreased translation. Vascular hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-β1-TGF-β3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF-β1-TGF-β3 and subsequent hypertension. Consistent with findings attained in mouse models, arteries recovered from hypertensive human patients displayed increased P311 expression. Thus, we identified P311 as the first protein known to modulate TGF-β translation and the first pan-regulator of TGF-β expression under steady-state conditions. Together, our findings point to P311 as a critical blood pressure regulator and establish a potential link between P311 expression and the development of hypertensive disease.
MICROSCOPICAL AND CHEMICAL EXAMINATION OF STOOLS IN YOUNG CHILDREN
Authors: E. Cassie, U. Cox
Journal: BMJ (1927)

rMZDLL BRIEA d59 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.Eicl .oulaid up for a week.When I saw him lhe was the subject of chlronic inidigestion of tlle appendical type.He was taking bromide regularly to control his epilepsy.. Operation was advised (1) for relief of the indigestion, (2) in the lhope that it might benefit the epilepsy.A large, distended, adherent appendix was removed from the ileo-caecal angle.He made an uneventful recovery.He had no epileptic attack for six monlths after operation, and since that time the attacks have been much less frequent and less severe.
Presidential disability and the twenty-fifth amendment
Authors: B. J. Lee
Journal: JAMA (1995)

To the Editor.  —In the December 7, 1994, issue, Drs Link and Toole, 1 Dr Joynt, 2 and President Carter 3 discussed the Twenty-fifth Amendment. They described difficulties with the drafting of the document and with its execution.  During the first year I served in the White House as physician to the president under President George Bush (1989-1993), I spent considerable time and effort with other key aides to the president on drafting a proper document, agreed on by all concerned, for the execution of this amendment. The president, Barbara Bush, the vice president, the office of counsel to the president, the chief of staff, the press secretary, the National Security Office, the director of administration for the White House, the deputy assistant to the president, and the director of the Secret Service were all intimately involved. As physician to the president, it was my role to determine disability. President
Editorial
Authors: HOWARD B. BURCHELL
Journal: Circulation (1963)

RECENT editorials1' 2 pointed out the haz- ards of external cardiac pacemakers powered by the house electric source if oper- ated concurrently with other electric appara- tus attached in any way to the patient.The titles of these editorials were perhaps not so successful in alerting the profession to the perils of iatrogenic electrocution as they might have been if the emphasis had been placed on the use of any electric appliance in the cardio- vascular laboratory, hospital room, or surgical theater when electrodes were in or on the heart.Recent reports have indicated that the car- diac catheter, filled with blood, saline, or a metal stiffener, may be the pathway of current from the patient's body to the "ground" and that such current may initiate ventricular fibrillation.3 4 After two instances of ven- tricular fibrillation (both patients were resus- citated successfully), Stanley Briller told me that he found an alternating current potential of approximately 50 volts between the case of a motor-driven injector and the ground; he calculated that a current of 100 to 200 micro- amperes might have flowed into the heart.When the apparatus was properly grounded, no further difficulty occurred.One must sus- pect that an electric hazard such as this may have contributed to occasional deaths during
Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non–Small-Cell Lung Cancer
Authors: Hak Choy, Lee S. Schwartzberg, Shaker R. Dakhil, Edward B. Garon, David E. Gerber, Janak K. Choksi, Ramaswamy Govindan, Guangbin Peng, Andrew Koustenis, Joseph Treat, Coleman Obasaju
Journal: Journal of Thoracic Oncology (2013)
Ga-67 Scintigraphy in Pulmonary Blastoma in a Child
Authors: ROBERT HOWMAN-GILES, LUCIANO DALLA POZZA, ROGER UREN
Journal: Clinical Nuclear Medicine (1993)

Pulmonary blastoma is a rare primary malignancy of the lung with a small number of cases reported in children. The primary treatment is surgery, however radiotherapy and chemotherapy are also used. The ability to determine whether the tumor has been fully removed and when recurrence occurs is important for appropriate treatment and prognosis. A case of a 7-year-old girl with pulmonary blastoma is reported in which the primary tumor is extremely Ga-67-avid and in which the gallium scans were helpful in determining early recurrence and metastatic disease to the brain.
Blood flow distribution within skeletal muscle during exercise in the presence of chronic heart failure: effect of milrinone.
Authors: H Drexler, F Faude, S Höing, H Just
Journal: Circulation (1987)

Recent studies suggest that, in the presence of heart failure, the capability of skeletal muscle to utilize delivered flow may be impaired due to maldistribution of blood flow within working muscle. Similarly, this mechanism could explain the failure of drugs to improve maximal oxygen consumption (VO2max) immediately. Accordingly, we assessed muscular blood flow distribution (ml/min/g, radioactive microspheres, 15 +/- 5 micron) among and within working muscle, VO2max, and arterial lactate in a rat preparation of myocardial infarction and heart failure (infarct size 36.0 +/- 3.3% of the left ventricle, n = 9), and in sham-operated animals (n = 11). Data were obtained at maximal treadmill exercise during alternate infusions of milrinone and saline. Total skeletal muscle blood flow during exercise was significantly lower in the infarction group (p less than .05 vs sham); reduced blood flow was primarily attributed to decreased flow to oxidative working muscle such as soleus and the red portion of gastrocnemius, whereas blood flow to glycolytic muscle portions (e.g., gastrocnemius white, vastus lateralis white) was similar in the infarction and sham-operated groups. Milrinone increased flow to the glycolytic working muscle portions in sham-operated animals (e.g., vastus lateralis white, 0.23 vs 0.29, p less than .05); by contrast, blood flow to the oxidative muscle fibers was increased in the infarction group (e.g., gastrocnemius red, 1.45 vs 1.87, p less than .05). Arterial lactate levels at similar workloads during exercise were higher in the infarction group (p less than .05). Neither lactate nor VO2max were significantly altered with milrinone in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
THE WORK OF THE AMERICAN PHARMACEUTICAL ASSOCIATION IN RELATION TO THE MATERIA MEDICA OF THE FUTURE.
Authors: F. E. STEWART
Journal: JAMA (1899)

On account of the high degree of learning and skill required in its practice and the philanthropic nature of the calling, medicine is classed as a liberal profession. The primary object of medical practice being to discover and remove the causes of disease, and secondarily to cure those who are afflicted, it is also classed as a philanthropic profession. Because of the great extent of the evil to the community resulting from ignorance and incompetency in the practice of the medical arts, entrance to the medical profession is hedged about with protective laws. Those laws are destined to limit the vocation to persons who are specially educated and trained for the practice. If the actual effects of ignorance, cupidity and pretence could be plainly stated, it would be instantly seen that a vocation in which health and life are at stake is in need of such systematic regulation. The people
Inflammation, Atherosclerosis, and Aspects of Insulin Action
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2005)

At the American Diabetes Association Postgraduate Course held in New York on 5 February 2005, Alan Chait (Seattle, WA) discussed C-reactive protein (CRP). Although it may not be as predictive of cardiovascular disease (CVD) as cholesterol, hypertension, and cigarette use (1), CRP appears to be the strongest “novel” risk factor thus far identified, showing greater predictive power than homocysteine, interleukin (IL)-6 (2), and other inflammatory markers, such as serum amyloid A (SAA), circulating levels of which parallel CRP, and intracellular adhesion molecule (ICAM)-1. CRP adds prognostic information at all levels of risk based on Framingham score (3).

Chait noted that several studies have shown that persons with diabetes without prior myocardial infarction have increased CVD risk, either to the same degree as persons without diabetes but with prior evidence of CVD (4,5) or to a somewhat lower level (6). An important potential linkage between diabetes and atherosclerosis may involve inflammatory factors. CRP is increased by diabetes, as well as by obesity, estrogen, cigarette smoking, chronic infections such as gingivitis, and chronic inflammatory diseases such as rheumatoid arthritis, while being decreased by statins (7), fibrates, niacin, aspirin (8), α-tocopherol (in high dose), thiazolidinediones (TZDs) (9), alcohol, and lifestyle factors such as exercise and weight loss (10), with weight loss also decreasing IL-6 levels (11). CRP increases if one simply counts the number of positive metabolic syndrome markers, dyslipidemia, upper-body obesity, hypertension, and hyperglycemia (12). Furthermore, Chait noted, CVD prevalence is greater in persons with metabolic syndrome without diabetes than in those with diabetes who do not have the metabolic syndrome (13). Similarly, a study of persons from Botnia in Finland showed, that for all levels of glycemia, the presence of metabolic syndrome is associated with an increase in CVD prevalence (14). The metabolic syndrome, then, is both associated …
Immunopathology of the placenta in pemphigoid gestationis and linear IgA disease
Authors: SUSAN E. KELLY, S. FLEMING, B.S. BHOGAL, F. WOJNAROWSKA, M.M. BLACK
Journal: British Journal of Dermatology (1989)

We have investigated the immunopathology of the placenta in bullous diseases by studying the deposition of immune complexes and expression of MHC class II subregion products by immunohistological methods. Placentae from seven patients with pemphigoid gestationis (PG) and two patients with linear IgA disease were studied. In PG immune complexes containing IgGI and C3 were identified in six cases. In linear IgA disease IgAI containing immune complexes were found in both cases. Placentae from patients with PG showed aberrant expression of MHC Class II products. This was not seen in the placentae from patients with linear IgA disease. In PG there was incoordinate expression of the subregion products, DP and DR being more extensively and consistently expressed than DQ. These results and previous immunogenetic studies suggest that PG may be unique among organ specific autoimmune disease, the autoantibodies forming during an allogenic response rather than target cells behaving as antigen presenting cells.
Respiratory syncytial virus replication in human lung epithelial cells: inhibition by tumor necrosis factor alpha and interferon beta.
Authors: R Merolla, N A Rebert, P T Tsiviste, S P Hoffmann, J R Panuska
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Respiratory syncytial virus (RSV) is the major pathogen causing severe lung disease in children. RSV initially replicates efficiently in the respiratory tract but becomes undetectable by 7 to 21 d after infection in normal children, suggesting that intrinsic cellular mechanisms, as yet undefined, may restrict virus replication. To provide an in vitro model to examine mechanisms that restrict RSV replication, three human lung epithelial cell lines were exposed to RSV in vitro and virus replication proceeded in a dose- and time-dependent manner, although less efficiently than the highly permissive CV-1 cell line (monkey kidney epithelial cell). Tumor necrosis factor alpha (TNF alpha) and/or interferon beta (IFN beta) markedly inhibited RSV replication in a dose- and time-dependent manner. TNF alpha combined with IFN beta essentially aborted RSV replication in A549 epithelial cells. TNF alpha and/or IFN beta did not induce cell membrane damage, cause cell lysis, or inhibit cellular protein synthesis. RSV-infected human alveolar macrophages, which produce TNF alpha, failed to productively infect lung epithelial cells in co-culture. Together these studies suggest that endogenous TNF alpha coupled with exogenous IFN beta could restrict RSV replication in lung epithelium.
PAPILLARY CYSTADENOMA OF THE KIDNEY ASSOCIATED WITH MYOMA OF THE UTERUS AND SPINAL CARIES
Authors: GEORGE ERETY SHOEMAKER
Journal: JAMA (1910)

\p=m-\Thepatient presented an unusual series of lesions, namely, uterine myoma with hemorrhage, spinal car- ies and kyphosis, together with a large bleeding tumor of the
Novel HIF2A mutations disrupt oxygen sensing, leading to polycythemia, paragangliomas, and somatostatinomas
Authors: Chunzhang Yang, Michael G. Sun, Joey Matro, Thanh T. Huynh, Shervin Rahimpour, Josef T. Prchal, Ronald Lechan, Russell Lonser, Karel Pacak, Zhengping Zhuang
Journal: Blood (2013)
ACUTE DELIRIUM APPARENTLY DUE TO BROMIDIA POISONING
Authors: A. E. Bennett
Journal: JAMA (1922)

<h3>History.</h3> —Mrs. R. B., aged 32, white, actress, admitted to the service of Dr. M. H. Bochroch in the psychopathic wards of the Philadelphia General Hospital, June 5, 1922, was unconscious, May 30, when her husband arrived home in the evening. In about ten minutes she revived, and talked rationally. That night she became delirious and talked at random, but had no fever. The next day she imagined that she was receiving electric shocks; she heard voices saying bad things about her, and thought that people were persecuting her father, and also trying to kill her with radio. No visual hallucinations were present. The history was unimportant until December, 1920, when the patient developed a pelvic inflammatory condition. At this time a physician prescribed Bromidia for insomnia. The patient took from one-half to 1 ounce daily of her own accord for nervousness, sleeplessness and pain for eighteen months. On admission,
Vitamin B_12 Deficiency After Gastric Surgery
Authors: ROBERT LEBOW
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 January 1985Vitamin B12 Deficiency After Gastric SurgeryROBERT LEBOW, M.D., MAY L. VOTAW, M.D., STEPHEN ROYAL, M.D.ROBERT LEBOW, M.D.Search for more papers by this author, MAY L. VOTAW, M.D.Search for more papers by this author, STEPHEN ROYAL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-1-139_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Schilling and associates (1) are to be commended for their fine study showing vitamin B12 deficiency and the probable need for B12 supplementation after gastric bypass surgery for obesity.Internists should be cautioned, however, that these results apply only to patients who have had the original gastric bypass procedure and not the gastroplasties now in vogue (the latest variation of which is the vertical banded gastroplasty). These gastroplasties are thought to be more physiologic and therefore less likely to lead to the complications some foresaw with the earlier gastric bypass procedure (2-4). The newer procedures remain to...References1. SCHILLINGGOHDESHARDIE RPG. Vitamin B12 deficiency after gastric bypass surgery for obesity. Ann Intern Med. 1984;101:501-2. LinkGoogle Scholar2. MASON E. Surgical treatment of obesity. In: EBERT PA, ed. Major Problems in Clinical Surgery. Philadelphia: W.B. Saunders Company. Google Scholar3. KRAL J. Surgical therapy. In: GREENWOOD MRC, ed. Obesity. New York: Churchill Livingstone; 1983:75-88. Google Scholar4. SOLOW C. Surgical treatment of obesity. In: GOODSTEIN RK, ed. Eating and Weight Disorders: Advances in Treatment and Research. New York: Springer Publishing Company; 1983:32-40. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: East Tennessee State University Johnson City, TN 37614 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1985Volume 102, Issue 1Page: 139-139KeywordsGastroenterology and hepatologyObesitySurgeryVitamin B12 deficiency Issue Published: 1 January 1985 PDF downloadLoading ...
Experimental Bacterial Endocarditis Due to Streptococcus Mitis
Authors: ROBERT A. RABENS, ALFRED G. KARLSON, JOSEPH E. GERACI, JESSE E. EDWARDS
Journal: Circulation (1955)

Pathologic and bacteriologic studies were carried out in all 24 dogs subjected to arteriovenous anastomoses and bacteremia. The single etiologic agent, Streptococcus mitis , was stained and cultured from 10 of the 11 hearts with active endocarditis (one animal had a healed tricuspid valvulitis) and from 16 of 17 animals with patent fistulas and active caval vegetations. The latter lesions occurred shortly after the initiation of injections and served as an important source of bacteria to the blood stream and heart valves. The endocarditis resembled that found in human cases with destructive and reparative phenomena coexisting. Focal myocarditic lesions and cardiac failure were noted only in animals with endocarditis. The other secondary (embolic) lesions were similar to those seen in man with the exception that in the dog the lesions had a suppurative tendency. Acute diffuse proliferative glomerulonephritis was found in animals with endocarditis and in those with infected fistulas and bacteremia.
Urinary Urgency and Acute Intrarenal Bleeding
Authors: Chan Ma, John Wagner, John Maesaka
Journal: Annals of Internal Medicine (1991)

Letters15 August 1991Urinary Urgency and Acute Intrarenal BleedingChan Ma, MD, John Wagner, MD, John Maesaka, MDChan Ma, MDSearch for more papers by this author, John Wagner, MDSearch for more papers by this author, John Maesaka, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-4-330_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: Urinary urgency is a common manifestation of bladder hyperactivity and irritability, usually resulting from obstruction, inflammation, or neuropathic bladder disease (1). We report two cases of acute-onset, severe urinary urgency unassociated with bladder disease and probably caused by acute intrarenal arterial bleeding.In the first case, a 34-year-old woman experienced an acute, frantic urge to urinate during renal biopsy as the biopsy needle was withdrawn. She was able to void only a small amount at the time. The sensation of severe urgency lasted for almost 2 hours. She started to pass blood clots within 30 minutes of...Reference1. McAninch J. Symptoms of disorders of the genitourinary tract. In: Tanagho EA, McAninch JW; eds. Smith's General Urology. 12th ed. Norwalk, Connecticut: Appleton & Lange; 1988:34-5. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Long Island Jewish Medical Center New Hyde Park, NY 11042 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1991Volume 115, Issue 4Page: 330-330KeywordsBiopsyBladderHemorrhageInflammationThrombosisUrination Issue Published: 15 August 1991 PDF downloadLoading ...