tbuckley/cabot-search huggingface dataset:
Abstract 2847: PECAM-1 targeting extends overall survival in various advanced metastatic mouse tumor models
Authors: Chakkrapong Handumrongkul, Chris Collins, Horace DeLisser, Mohammed Kashani-Sabet, Cory Nadel, Mehdi Nosrati, Bruce Keyt, Christopher Haqq, Sylvia Fong, Robert J. Debs
Journal: Cancer Research (2012)

Abstract Objectives: Patients who die from cancer succumb to advanced metastatic progression (AMP). While targeted therapies are available that address tumor cell derived regulators of metastasis, few therapeutics are being developed to address the molecular mechanisms of AMP. Our group has previously shown that vascular endothelial cell (VEC) PECAM-1 is a critical molecular master switch which regulates AMP by controlling the release of VEC-derived, paracrine growth factors that drive its progression. Anti-PECAM-1 monoclonal antibody (mAb) effectively and safely treats even pre-terminal cancers in AMP-bearing mice. The current experiments were performed to assess whether, to what extent and how widely targeting PECAM-1 can improve overall survival in mice bearing advanced metastases. Methods: Groups of wildtype (WT) C57Bl/6 mice, together with age and gender matched PECAM-1 knockout (KO) mice were intravenously injected with 25,000 murine B16-F10 melanoma cells, 30,000 murine EL4 lymphoma cells or 1,000,000 murine MC38 colon cancer cells. We then injected matched groups of PECAM-1 KO vs WT mice with 1,000,000 B16-F10 cells, to model maximally aggressive AMP. All groups were assessed for overall survival, using IACUC approved guidelines. Results: In all cases, overall survival (OS) was significantly prolonged in PECAM-1 KO vs WT controls (Kaplan-Meier ranged from p = 0.018 to p = 0.0002). Targeting microenvironmental PECAM-1 was as effective in increasing OS in mice receiving the very high tumor burden of 1,000,000 B16-F10 cells as in mice receiving 25,000 cells, further confirming the efficacy of targeting PECAM-1 against the most advanced models of metastasis that can be achieved preclinically. Furthermore, anti-PECAM-1 mAb-based therapy of B16-F10 metastase was as effective as the PECAM-1 KO genotype in increasing OS. Conclusion: To date, many approved mAb- and small molecule-inhibitor based targeted-therapies have shown limited abilities to either prolong OS as single agents, or to effectively treat multiple different solid tumor types. These results suggest that anti-PECAM-1 mAb therapy, which specifically targets VEC and paracrine factors they produce, has the potential to significantly increase OS in the setting of lethal advanced metastatic progression, independent of tumor type. Anti-PECAM-1 mAb therapy is as effective as a PECAM-1 knockout in improving OS. Phase 1 clinical trials are planned within 2 years. 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 2847. doi:1538-7445.AM2012-2847
Tighter controls are needed to root out bogus patient groups
Authors: Zosia Kmietowicz
Journal: BMJ (2004)

Patient organisations need to be more tightly regulated to protect the public from bogus groups and undue influence from the pharmaceutical industry and other funding bodies, MPs heard last week.

Setting standards on transparency and accountability would help to distinguish legitimate patient groups from those set up by drug companies to promote awareness of a specific condition and drugs to treat it, said witnesses at the fourth public hearing of the health committee's inquiry into the influence of the pharmaceutical industry.

There are more than 200 national patient groups in the United Kingdom and many rely on funding …
Performance of individual surgeons to be published
Authors: A. Vass
Journal: BMJ (2002)

The performance of individual cardiothoracic surgeons is to be published, in a drive to create a more open, honest, and patient centred NHS.

The plan is one of several initiatives announced by the government last week in response to the report of the Kennedy inquiry into heart surgery in children at the Bristol Royal Infirmary ( BMJ 2001;323:181-2324:7331:189:1).

An independent office for information on healthcare performance is to be set up—as an arm of the Commission for Health Improvement—which will, by April 2004, release data on mortality within 30 days of surgery. Data collection methods have been developed by the Society of Cardiothoracic Surgeons, which has agreed to cooperate with the initiative.

From 2005, results will be published annually for each heart surgery centre and every three years for each cardiac surgeon.

The 200 page report has taken over six …
Primary Care Medicine
Authors: Elliott B. Oppenheim
Journal: JAMA (1981)

As the money crunch affects all levels of society, precious library acquisitions must be more carefully planned than ever before. There is substantial reason to include Goroll, May, and Mulley's<i>Primary Care Medicine</i>in a personal reference library. It is a book of substance that bridges a gap unfilled by traditional internal medicine treatises, or Conn, Rakel, and Johnson's<i>Family Practice</i>(Philadelphia, WB Saunders Co, 1978). This is not a sophisticated compendium of up-to-the-minute abstract treatment philosophy and theory, but a methodical checklist for medical analysis and therapy. The authors consider the panorama of approaches to, and the evaluation and management of, problems from bacteriuria to yellow fever vaccine, from xanthinuria to abdominal pain. But there is little esoterica. The practicing physician in a quandary about monitoring the condition of a patient with colonic cancer will find the relevant answers in this volume. So will answers be found for the
Co-infection with Esptein-Barr Virus and Bartonella henselae Resulting in Systemic Bartonellosis
Authors: None Liana Signorini, None Francesca Simeone, None Luca Tonegatti, None Paolo Colombini, None Barbara Cadeo, None Francesco Cristini, None Alberto Matteeli, None Pierluigi Viale
Journal: Journal of Infection (2002)
Transplantation Pioneer Predicts Successful Xenotransplantation Soon
Authors: Andrew A. Skolnick
Journal: JAMA (1993)

DESPITE the failure of two patients to survive with baboon liver grafts, transplantation pioneer Thomas E. Starzl, MD, PhD, predicts that successful liver xenotransplantation may be achieved within the next year. Delivering the keynote address, "Xenografts vs Bionics for the 21st Century," at the 39th Annual Meeting of the American Society of Artificial Internal Organs (ASAIO), in New Orleans, La, Starzl described his group's latest findings. He says that they may point the way to successful transplantations using organs from baboons or even pigs and other animals. See also p 3040. According to Starzl, who is professor of surgery and director of the Pittsburgh Transplant Institute at the University of Pittsburgh, Pa, a recent discovery is responsible for his optimism. This discovery, that successful allograft transplants produce a chimeric mixture of donor and recipient cells within the transplanted organ and in the recipient's skin, heart, lymph nodes, small intestines, and
Blocking Macrophage Leukotriene B <sub>4</sub> Prevents Endothelial Injury and Reverses Pulmonary Hypertension
Authors: Wen Tian, Xinguo Jiang, Rasa Tamosiuniene, Yon K. Sung, Jin Qian, Gundeep Dhillon, Lajos Gera, Laszlo Farkas, Marlene Rabinovitch, Roham T. Zamanian, Mohammed Inayathullah, Marina Fridlib, Jayakumar Rajadas, Marc Peters-Golden, Norbert F. Voelkel, Mark R. Nicolls
Journal: Science Translational Medicine (2013)

Pulmonary hypertension (PH) is a serious condition that affects mainly young and middle-aged women, and its etiology is poorly understood. A prominent pathological feature of PH is accumulation of macrophages near the arterioles of the lung. In both clinical tissue and the SU5416 (SU)/athymic rat model of severe PH, we found that the accumulated macrophages expressed high levels of leukotriene A4 hydrolase (LTA4H), the biosynthetic enzyme for leukotriene B4 (LTB4). Moreover, macrophage-derived LTB4 directly induced apoptosis in pulmonary artery endothelial cells (PAECs). Further, LTB4 induced proliferation and hypertrophy of human pulmonary artery smooth muscle cells. We found that LTB4 acted through its receptor, BLT1, to induce PAEC apoptosis by inhibiting the protective endothelial sphingosine kinase 1 (Sphk1)-endothelial nitric oxide synthase (eNOS) pathway. Blocking LTA4H decreased in vivo LTB4 levels, prevented PAEC apoptosis, restored Sphk1-eNOS signaling, and reversed fulminant PH in the SU/athymic rat model of PH. Antagonizing BLT1 similarly reversed established PH. Inhibition of LTB4 biosynthesis or signal transduction in SU-treated athymic rats with established disease also improved cardiac function and reopened obstructed arterioles; this approach was also effective in the monocrotaline model of severe PH. Human plexiform lesions, one hallmark of PH, showed increased numbers of macrophages, which expressed LTA4H, and patients with connective tissue disease-associated pulmonary arterial hypertension exhibited significantly higher LTB4 concentrations in the systemic circulation than did healthy subjects. These results uncover a possible role for macrophage-derived LTB4 in PH pathogenesis and identify a pathway that may be amenable to therapeutic targeting.
More pieces of the platelet activation puzzle slide into place
Authors: Lawrence F. Brass
Journal: Journal of Clinical Investigation (1999)

Platelets are normally activated at sites of vascular injury by a combination of collagen exposure, local thrombin generation, and the release of ADP from damaged cells and other activated platelets. Drugs targeting ADP receptors have proved to be clinically useful in settings where platelet activation contributes to arterial thrombosis. However, until the past few years, relatively little was known about the mechanisms by which platelets respond to ADP. Indirect evidence suggested that 1 or more G proteins and G protein–coupled receptors were involved, but none of the receptors known to respond to adenine nucleotides appeared to have the necessary pharmacological profile. In vitro, ADP causes platelets to change shape (undergo cytoskeletal reorganization), secrete their storage granules, expose binding sites for fibrinogen on the αIIbβ3 integrin, and aggregate. These events all require an increase in cytosolic Ca2+ concentration and are facilitated by the ability of ADP to inhibit cAMP formation by adenylyl cyclase (1, 2).
Lack of C/EBP? gene expression results in increased DNA synthesis and an increased frequency of immortalization of freshly isolated mice hepatocytes
Authors: Humberto E. Soriano, Dong C. Kang, Milton J. Finegold, John M. Hicks, Nai-Dy Wang, Wilbur Harrison, Gretchen J. Darlington
Journal: Hepatology (1998)

The CCAAT/enhancer binding protein α (C/EBPα) binds to specific promoter sequences and directs transcription of many genes expressed in the liver. Overexpression of C/EBPα in established cell lines inhibits cell proliferation. Primary hepatocytes from newborn C/EBPα(−/−) mice and normal littermates were used to determine whether the absence of C/EBPα increased proliferation and/or transformation of these cells in vitro . DNA synthesis, as measured by bromodeoxyuridine (BrdU) incorporation 24 hours postharvest, was fourfold higher in cells from C/EBPα(−/−) pups. Established cell lines were derived from 7 of 8 hepatocyte cultures initiated from null mutants, 4 of 23 cultures from heterozygotes, and 0 of 12 cultures from wild-type animals. C/EBPα(−/−) cultures had epithelial morphology, showed bile canaliculi, and expressed albumin messenger RNA (mRNA). When cultured on Matrigel, which promotes differentiation, cell lines derived from C/EBPα(−/−) mice formed cords and increased albumin mRNA expression by 1.7- to 3.8-fold. C/EBPα(−/−) cell lines exhibited rapid growth and rapid accumulation of chromosomal abnormalities, and were capable of forming nodules when inoculated into the abdominal subcutaneous tissue of nude mice. Our data show that C/EBPα is an important regulator of hepatocyte proliferation and participates in the maintenance of the nontransformed hepatic phenotype in vitro .
Are research ethics committees behaving unethically? Some suggestions for improving performance and accountability
Authors: J. Savulescu, I. Chalmers, J. Blunt
Journal: BMJ (1996)

The results of recent empirical investigations in research synthesis imply that research ethics committees are behaving unethically by endorsing new research which is unnecessary and by acquiescing in biased under-reporting of research which they have approved. The performance and accountability of research ethics committees would be improved if they required those proposing research to present systematic reviews of relevant previous research in support of their applications; to summarise the results of these reviews in the information prepared for potential participants; to register new controlled trials at inception; and to ensure that the results of these trials are made publicly available within a reasonable period of time after completion of data collection.
Effect of Hepatocellular Injury on Gastric Secretion.
Authors: W. Silen
Journal: Annals of Internal Medicine (1963)

s1 April 1963Effect of Hepatocellular Injury on Gastric Secretion.W. Silen, M.D.W. Silen, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-725_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is well established that cirrhosis of the liver is associated with a greater incidence of peptic ulceration than that in the general population. The mechanisms by which this occurs have been unknown heretofore, particularly since controlled studies of the effect of hepatocellular injury upon gastric secretion have been unavailable. The following experiments have been carried out to elucidate some of these questions.Hepatocellular injury has been induced in dogs equipped with denervated fundic gastric pouches by prolonged feeding of a mixture of carbon tetrachloride and alcohol. Frank cirrhosis of the liver develops in approximately 12 to 16 months in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 725-725KeywordsAlcoholsCirrhosisLiverPeptic ulcersTetrachloride ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
POST-TRAUMATIC ANGIOMA.*
Authors: F. FOLDVARI
Journal: British Journal of Dermatology (1935)

Journal Article POST‐TRAUMATIC ANGIOMA.* F. FÖLDVÁRI, M.D. F. FÖLDVÁRI, M.D. Search for other works by this author on: Oxford Academic Google Scholar *From the Clinic of Dermatology and Syphilology of the Royal Hungarian Petrus Pázmány University of Budapest; L. Nékám, M.D., Professor of Dermatology and Syphilology, Director. Author Notes British Journal of Dermatology and Syphilis, Volume 47, Issue 11, 1 November 1935, Pages 463–467, https://doi.org/10.1111/j.1365-2133.1935.tb10222.x Published: 01 November 1935
Some Clinical Features of Complete Heart Block
Authors: GEORGE B. PENTON, HAROLD MILLER, SAMUEL A. LEVINE
Journal: Circulation (1956)

A review was made of 251 cases of complete heart block. They were divided into the following groups: coronary artery disease (nonacute), 58 cases; myocardial infarction (acute), 49 cases; hypertensive heart disease, 62 cases; rheumatic heart disease, 21 cases; miscellaneous, 16 cases; "etiology undetermined," 18 cases; and digitalis intoxication, 27 cases. Among the various clinical features analyzed were the sex and age factors, the occurrence of syncope, palpitation, congestive failure, anginal pain, and the duration of life after the onset of major symptoms. Methods of treatment are discussed.
Pilot study could cut medical negligence costs
Authors: C. Dyer
Journal: BMJ (1995)

An experiment in resolving medical negligence cases by mediation rather than costly and lengthy court proceedings got under way this week in Britain. The pilot scheme, backed by the Department of Health, is to go ahead in two regions--Anglia and Oxford, and Northern and Yorkshire.

Its first case was due to be tackled this Thursday, after the BMJ went to press. Hinchingbrooke NHS Health Care Trust in Huntingdon, Cambridgeshire, and a patient who had two stillbirths at Hinchingbrooke Hospital have agreed to try to settle the case through mediation.

Now mainly used in …
Simultaneous Tubal and Uterine Pregnancy
Authors: A. Rhodes, A. R. Snead
Journal: BMJ (1967)

BxImi 447 both at 6 p.m. and midnight and in addition are either at the upper limit of normal or frankly elevated at 9 a.m.Further, they may show increased resistance to suppression with dexamethasone.These abnormalities appear to return to normal with remission of the depressed state.The high plasma 11- O.H.C.S. levels reported in the cases of con- gestive cardiac failure can be explained as a response by the adrenal cortex to the severe stress of their illness.We have found that in many types of stressful situation the normal diurnal rhythm is abolished, and furthermore a plasma 1l-O.H.C.S. level of 30 pg./100 ml.
The isovolumic contraction time of the left ventricle. An echographic study.
Authors: S Hirschfeld, R Meyer, J Korfhagen, S Kaplan, J Liebman
Journal: Circulation (1976)

The echographic isovolumic contraction time (ICT) of the left ventricle (LV) was measured in order to assess alterations of LV performance in children with various forms of cardiac disease. The echographic ICT was defined as the interval between coaptation of the anterior and posterior mitral valve leaflets and aortic cusp opening. Four groups of patients were evaluated: normal (48); LV myocardial disease (20); patent ductus arterosus (PDA) (19); and aortic stenosis (AS) (15). In normal children ICT shortened with decreasing age and increasing heart rate. Isovolumic contraction time was more influenced by heart rate (HR) than age, but the relationship was still weak (r = 0.61). In patients with LV myocardial disease ICT was markedly prolonged, while in children with patent ductus arteriosus and aortic stenosis it was shortened as compared with normal children (P less than 0.01).
Primary cutaneous nocardiosis due to Nocardia nova in a healthy woman .
Authors: A. Shimizu, O. Ishikawa, Y. Nagai, Y. Mikami, K. Nishimura
Journal: British Journal of Dermatology (2001)

We describe a 68‐year‐old healthy woman with an unusual skin manifestation of mycetoma. A dark reddish erythematous plaque was present on the dorsum of the left hand for over 10 years. A skin biopsy revealed sulphur granules in the abscess, and Nocardia nova was identified from the specimen. Treatment with dapsone resulted in significant improvement. We review the clinical features of cutaneous N. nova infections.
CONGENITAL ABSENCE OF THE ESOPHAGUS.
Authors: DANIEL LICHTY
Journal: JAMA (1896)

A writer in a late issue of theJournal, in an article on a subject remote from this, made the statement that " malformations of the<i>internal</i>organs of the fetus are still more rare than the various orthopedic lesions of the exterior body." In confirmation of this, a case of the above title came to my notice, whose rarity then impressed me, and it is here given to add to the peculiarities and mysteries of tissue growth in pre-natal life. If those who have the Index Medicus can find similar cases recorded in it, it would be interesting to know of them. There was born in Rockford Hospital July 24,1895, after a quite natural and easy labor, of a healthy Swedish mother aged 25, her third child, a male weighing six and three-fourths pounds, well formed and fully developed in all its external parts. After birth there was some of
Lesson of the week: Postoperative pressure sores after epidural anaesthesia
Authors: J L Shah
Journal: BMJ (2000)

Pressure sores may occur when epidural analgesia produces profound sensory and motor block 

Epidural anaesthesia and analgesia provide a better outcome after major surgery.1 Side effects of epidural such as dural puncture, motor block, and hypotension are well known. Epidural analgesia may also cause pressure sores in elderly and debilitated patients.2 The general belief is that pressure sores do not occur in patients who are fit and mobile. This report describes three cases of heel ulcers in fit young patients related to pressure after epidural analgesia. None of the patients had any predisposition to pressure related ulceration. In two of the patients the heel ulcers became apparent several days after surgery.

Case 1— A 52 year old woman weighing 42 kg had carcinoma of the vulva. She was otherwise fit and active. She smoked 20 cigarettes a day. She had a radical vulvectomy and bilateral inguinal lymphadenectomy under combined general and epidural anaesthesia. She was given 20 ml of 0.25% bupivacaine for epidural anaesthesia. To prevent pressure sores, the operating table was covered with silicon jelly pads. Surgery lasted about three hours. The patient was supine for the first 90 minutes and in the lithotomy position thereafter. Her preoperative blood pressure was 120/70 mm Hg. During surgery her systolic blood pressure varied between 85 and 90 mm Hg and her general condition was stable. She received a continuous epidural infusion of plain 0.15% bupivacaine for postoperative analgesia. She remained free of pain and was comfortable. Her systolic blood pressure varied between 75 and 85 mm Hg. She was unable …
Managing Weight Loss Expectations
Authors: Zhaoping Li, David Heber
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Oral Squamous cell carcinoma Managed by specialists from different disciplines
Authors: N R McLean, G P Feaver
Journal: BMJ (1994)

EDITOR, - Iain Hutchison states that “only six British medical schools offer any formal teaching in mouth examination by oral surgeons” and that “any patient with a red or white intraoral patch should attend their local oral surgery department as a matter of some urgency.”1

The investigation and management of cancer of the mouth and jaws is not the sole remit of oral surgeons but is an area in which there is an interface with many other specialties. As medical students in Glasgow, we were taught the examination of the oral cavity and the management of intraoral carcinoma by general surgeons; ear, nose, and …