tbuckley/cabot-search huggingface dataset:
Abstract 493: Endothelin-1 induces activation of vascular endothelial growth factor receptor-3 and modulates cell migration and vasculogenic mimicry in melanoma cells
Authors: Francesca Spinella, Valentina Caprara, Valeriana DiCastro, Laura Rosanò, Roberta Cianfrocca, Pier Giorgio Natali, Anna Bagnato
Journal: Cancer Research (2012)

Abstract Phenotypic and genotypic analyses of cutaneous melanoma have identified endothelin B receptor (ETBR) as tumor progression marker, thus representing a potential therapeutic target. We previously reported that the binding of ET-1 to ETBR stimulates angiogenesis and lymphangiogenesis directly and by stimulating vascular endothelial growth factor (VEGF)-A and VEGF-C production. In this study we investigated as to whether in melanoma cells ET-1 axis may interact with VEGF-A and VEGF-C signaling pathways to heighten cellular responsiveness. We found that in primary and metastatic melanoma cell lines, ET-1 increased VEGF-A, VEGF-C and its selective receptor VEGFR-3, at mRNA and protein level. Following ET-1 stimulation, VEGF-A and VEGF-C were upregulated, VEGFR-3 was rapidly phosphorylated and downstream signaling intermediates, such as p42/44 MAPK and Akt, were activated through ETBR. Inhibition of c-Src activity by PP2, reduced ET-1-induced VEGFR-3 phosphorylation, demonstrating that ET-1 transactivates VEGFR-3 through an intracellular mechanism mediated by c-Src. Stimulation with ET-1 in combination with VEGF-A or VEGF-C increased p42/44 MAPK and AKT phosphorylation, and resulted in a greater degree of melanoma cell migration compared to a single factor. Furthermore, this combination significantly enhanced the ET-1-induced vasculogenic differentiation of melanoma cells in capillary-like structures, vasculogenic mimicry, indicating that crosstalk between ET-1/ETBR axis with VEGFR-3/VEGF-C system may enhance cancer cell motility and invasiveness and contributes to the promotion of cancer metastasis. Finally, in melanoma xenografts, ETBR antagonist suppressed tumor growth and neovascularization-related effectors, indicating that targeting ETBR related signalling cascade may represent a novel treatment of melanoma by impairing the crosstalk between ET-1 axis and VEGF in melanoma. Supported by AIRC 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 493. doi:1538-7445.AM2012-493
San Francisco Bay Area Institutions Host AMA's Seventh Annual Reporters Conference
Authors: Timothy F. Kirn
Journal: JAMA (1988)

EVERY YEAR, at about the same time as an Indian summer, the American Medical Association (AMA) holds its annual science reporters conference. This year's, the seventh, was held with the cooperation of two of the San Francisco Bay Area's academic giants, Stanford University Medical Center and the University of California, San Francisco (UCSF). Last week's conference was held in a hotel on San Francisco's palm-lined Union Square, with 14 researchers and medical experts on the program. One afternoon was devoted to the topic of misconduct and fraud in medical research. (Please see accompanying article.) <h3>Scheduled to Speak</h3> The conference program included the following: Charles Epstein, MD, UCSF professor of pediatrics and biochemistry, has developed a model of Down's syndrome by endowing a mouse with three copies of the murine chromosome 16. Because this chromosome contains many of the same genes as the human chromosome 21, this trisomy mimics the trisomy
S62 Characterisation of a novel "pseudo-Z" variant of 1-antitrypsin
Authors: M.-P. Nyon, L. Segu, B. Roussel, N. Kalsheker, D. A. Lomas, K. Thalassinos, B. Gooptu
Journal: Thorax (2010)

The Z (Glu342Lys) variant of α<sub>1</sub>-antitrypsin is common in populations of North European descent. The mutation causes individual α<sub>1</sub>-antitrypsin molecules to assemble into polymer chains in the endoplasmic reticulum of hepatocytes. Z homozygotes (PiZZ) have circulating levels of α<sub>1</sub>-antitrypsin ∼15% of normal and are predisposed to hepatic cirrhosis and severe, early-onset emphysema. The risk of clinically significant disease associated with the heterozygote PiMZ state is minimal. We describe a case phenotyped as PiZZ during family screening, but with surprisingly preserved circulating α<sub>1</sub>-antitrypsin levels. Genotyping revealed compound heterozygosity for the Z mutation and a novel, “pseudo-Z” mutation. Biochemical and ion-mobility mass spectrometry characterisation of pseudo-Z α<sub>1</sub>-antitrypsin showed that it readily populated a polymerogenic intermediate state under physiological conditions. Cell biological studies of a series of α<sub>1</sub>-antitrypsin variants indicated these effects involved disruption of a hydrogen bond stabilising the F-helix-linker region of the protein structure. These data strongly support the hypothesis that stability of this region co-regulates formation of the polymerogenic intermediate. Whilst the intermediate form of pseudo-Z α<sub>1</sub>-antitrypsin is more stable than that of the true Z variant, the resultant polymers all share a characteristic neoepitope. Pseudo-Z α<sub>1</sub>-antitrypsin is thus a useful model for in vitro screening of potential lead compounds to bind the polymerogenic intermediate state, improving the ability to develop novel therapies to treat α<sub>1</sub>-antitrypsin deficiency. Our data predict that the likelihood of severe disease in the PiZ/Pseudo-Z compound heterozygote state will be increased relative to the PiMZ state, but far lower than for PiZZ individuals.
Thrombophlebitis Migrans and Carcinoma of Body and Tail of Pancreas
Authors: M. H. Oelbaum, S. J. Strich
Journal: BMJ (1953)

OXYGEN SATURATION OF BLOODEDICNALJ 907is simple and easily available.Two observers using the method can make duplicate estimations of the percentage oxygen saturation on 15 specimens of blood in one hour.A comparison between results obtained by spectro- photometric analysis and by standard manometric blood-gas analysis is reported in detail.We have much pleasure in making grateful acknowledgment to Dr. M. W. A. Gatman, of the Department of Medicine, the
Getting Well in Barranquilla
Authors: John L. McClenahan
Journal: JAMA (1972)

I was sitting in the Lounge of the<i>Algonquin Princess</i>after dinner, listening to the ship's orchestra scratch out a rumba, when Miss Holloway asked me the question. A slim, prehensile blonde from East Orange, perhaps 46 years of age, Miss Holloway would be dining at my right through the entire cruise. "Tell me, Johnny," she said, nibbling a peanut. "Have you had any unbelievably exciting adventures at sea?" "What did you have in mind?" I said. "You know perfectly well what I have in mind. Gory, fascinating things must happen all the time to ship's doctors in boats like this. Violent deaths, mutilating fractures, epidemics of plague or tetanus, breech deliveries during a screaming hurricane.<i>That</i>sort of thing." I considered her question carefully and allowed a little time to pass before answering. Fiction No. 3, I decided, would do very well under the circumstances. I had not used
Abstract P5-16-01: Survival advantage in patients with metastatic breast cancer receiving endocrine therapy plus Sialyl Tn-KLH vaccine: post hoc analysis of a large randomized trial
Authors: NK Ibrahim, JL Murray, D Zhou, EA Mittendorf, D Sample, M Tautchin, D Miles
Journal: Cancer Research (2012)

Abstract Background: A multicenter, double blinded, randomized phase III trial of the therapeutic cancer vaccine STn-KLH was completed in an international cohort of 1,028 women with metastatic breast cancer who had either no evidence of disease or nonprogressive disease following first-line chemotherapy. This trial is registered with ClinicalTrials.gov (No. NCT00003638). The outcomes showed that STn-KLH was safe and relatively well tolerated but had neither a positive nor negative effect on time to progression (TTP) or overall survival (OS) duration in the intent-to-treat population when compared with KLH control alone. The purpose of this post hoc analysis is to explore the potential benefit of combining an antiestrogen with MUC1 vaccines in metastatic breast cancer patients. Methods: The data were further explored to determine if a retrospective, reassigned endocrine subset patient stratification produces subgroups that may have experienced benefit in TTP or survival compared with the phase III trial ITT analysis. Results: Women treated with concomitant endocrine therapy, a pre stratified subset comprising approximately one third of the original study population, achieved a clinical benefit both in terms of TTP and survival compared with women who did not receive endocrine therapy. Moreover, women in the endocrine-treatment subset who mounted a median or greater antibody response (titer &amp;gt;1:320 toward bovine submaxillary mucin) to the STn-KLH vaccine experienced significantly longer median survival than their trial counterparts who mounted a below-median antibody response. Conclusion: Unlike maintenance chemotherapy, with its associated cumulative toxicity, the combination of endocrine and STn-KLH therapy may offer clinical benefit with few adverse effects for women with metastatic breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-01.
Oncostatin M Induces Growth Arrest by Inhibition of Skp2, Cks1, and Cyclin A Expression and Induced p21 Expression
Authors: Hartmut Halfter, Matthias Friedrich, Ansgar Resch, Michael Kullmann, Florian Stögbauer, E. Bernd Ringelstein, Ludger Hengst
Journal: Cancer Research (2006)

Abstract Oncostatin M has been characterized as a potent growth inhibitor for various tumor cells. Oncostatin M–treated glioblastoma cells cease proliferation and instigate astrocytal differentiation. The oncostatin M–induced cell cycle arrest in G1 phase is characterized by increased level of the cyclin-dependent kinase (CDK) inhibitory proteins p21Cip1/Waf1/Sdi1 and p27Kip1. Induction of p21 protein corresponds to increased mRNA level, whereas p27 accumulates due to increased stability of the protein. Interestingly, stabilization of p27Kip1 occurs even in S phase, showing that p27 stabilization is a direct consequence of oncostatin M signaling and not a result of the cell cycle arrest. Degradation of p27 in late G1 and S phase is initiated by the ubiquitin ligase complex SCF-Skp2/Cks1. Oncostatin M inhibits expression of two components of this E3 ligase complex (Skp2 and Cks1). Although combined overexpression of Skp2 and Cks1 rescues p27 degradation in S phase, it can not override p27 accumulation in G1 phase and cell cycle arrest by oncostatin M. In addition to increasing Cdk inhibitor level, oncostatin M also impairs cyclin A expression. Cyclin A mRNA and protein level decline shortly after oncostatin M addition. The accumulation of two CDK inhibitor proteins and the repression of cyclin A expression may explain the broad and potent antiproliferative effect of the cytokine. (Cancer Res 2006; 66(13): 6530-9)
Apparatus, With Non-Perishable Valves, for Administration of Nitrous Oxid and Ether, Separately or in Combination, Without Change of Inhalers.
Authors: S. ORMOND GOLDAN
Journal: JAMA (1900)

The essential part of the gas apparatus is a stop-cock con taining two valves. The inspiratory valve is set in an inner cylindrical tube, which works by a handle through a right-angled slit in an external cylinder supporting the expiratory valve superiorly, and inferiorly gives attachment to the gas bag. The valves themselves are made of thin sheet hard rubber, and are therefore non-shrinkable and stand all climates. When the handle is turned down to point indicated by "air," Fig. 1, the gas bag is closed by means of the obturating function of the inner tube; when the handle is turned upward, to place indicated by "gas," Fig. 2, air is excluded and gas is inhaled by means of the inspiratory valve. Expirations of thepatient pass out through the expiratory valve; at the same time the inspiratory valve is closed. During inspiration the inspiratory valve is opened at the same
Rickets and Osteomalacia in the Glasgow Pakistani Community, 1961-71
Authors: J. A. Ford, E. M. Colhoun, W. B. McIntosh, M. G. Dunnigan
Journal: BMJ (1972)

The prevalence of vitamin D deficiency was reassessed in April and May 1971, 10 years after the discovery of widespread late rickets and osteomalacia in the Glasgow Pakistani community. Evidence of vitamin D deficiency was found in 28 out of 115 adults and children examined (24%). Children at the age of puberty were most severely affected by rickets, whereas most infants and younger children in the survey were protected by vitamin D supplements. Mild biochemical osteomalacia was common in Pakistani women.A total of 21 Pakistani and Indian children with rickets were admitted to Glasgow hospitals during 1968-70. These comprised 10 children with infantile rickets and 11 with late rickets. Four of the latter group required osteotomy for severe rachitic deformity.Late rickets and osteomalacia in Pakistani and Indian immigrants are not primarily due to nutritional deficiency of vitamin D, though the high phytate content of their diet may be of aetiological importance. A combination of environmental, social, and endogenous factors, the relative importance of which is not at present clear, may also be involved. Advice on the prophylaxis of vitamin D deficiency should be given to all Pakistani and Indian communities in the United Kingdom.
Community physicians and administrators
Authors: P. MacMahon
Journal: BMJ (1976)

shown by the experience of Dr John Paulley (20 November, p 1252) in the Ipswich District.Together with the more favoured Cambridge and Norwich Districts they combine to put the East Anglian Region on the national average.Annual differential incremental growth money, not money stolen from the London till, is surely the only real solution for the future.But we may have to await the restora- tion of the nation's finances by the International Monetary Fund and forward-looking politicians.Incidentally, have the favoured regions used their extra millions this year productively or has the money paid for infla- tion and junior doctor's pay awards ?Of course RAWP is right in wishing to equate resources with medical need.However, first they must define "need" and then show how to measure it.Then they may bring the Tablets down from the Mountain.
Unusual Cause of Acute Abdomen
Authors: Donald T. King
Journal: JAMA (1977)

Splenic infarction under hypoxic conditions is a well-known complication of sickle cell trait (Hgb AS). However, this case illustrates that it may occur without any clinical conditions of circumstances associated with decreased Pao2. In addition, sickle cell trait should be included in the differential diagnoses of splenic infarction even if the patient is not of African ancestry.
THE RESULTS OF TWO HUNDRED CHROMO-URETEROSCOPIES EMPLOYING INDIGOCARMIN AS A FUNCTIONAL KIDNEY TEST
Authors: B. A. THOMAS
Journal: JAMA (1913)

The province of a functional kidney test, in my mind, is not so much to determine the diagnosis in a particular case as it is to prognose the sufficiency of the supposedly healthy twin organ. Often the precise nature of the kidney lesion can be definitely diagnosed without recourse to the estimation of the renal function—witness the skiagram in nephrolithiasis, palpation in conjunction with the other physical and clinical findings in renal tumor, etc. Moreover, it is often absolutely unimportant, from the point of view of treatment, to determine by functional kidney tests the extent of involvement as to sufficiency or non-suffciency of a kidney, the seat of such diseases as calculus, sarcoma, hypernephroma, surgical tuberculosis, etc. The paramount question to be decided is the unilateral or bilateral involvement of the organs and above all the functional integrity of the presumably healthful kidney. It is seldom that the functional test,
Combined-Modality Therapy of Locally Advanced Cervical Cancer
Authors: P. G. Rose
Journal: Journal of Clinical Oncology (2003)

Six randomized trials of chemoradiotherapy in cervical cancer have demonstrated improvement with cisplatin-based chemoradiotherapy compared with radiation alone or radiation with hydroxyurea. Only one randomized trial (Gynecologic Oncology Group [GOG] 120) compared different cisplatin-based regimens and demonstrated significantly more hematologic and gastrointestinal toxic effects with the combination of cisplatin, fluorouracil, and hydroxyurea than with weekly cisplatin alone. The use of fluorouracil and mitomycin as radiation sensitizers for cervical cancer is based on their activity in chemoradiotherapy for anal carcinoma. However, a three-fold increase in serious late bowel toxicity was seen in patients treated with fluorouracil and mitomycin compared with fluorouracil alone when combined with radiation therapy for cervical cancer. Another randomized trial demonstrated improvement in survival with fluorouracil infusion compared with radiation alone only in early-stage disease. However, the most recently completed randomized trial by the GOG, which compared continuous fluorouracil infusion with weekly cisplatin, was closed when interim analysis demonstrated no potential superiority to the fluorouracil arm. Uncontrolled studies have evaluated the use of carboplatin on several different schedules, but no controlled trials have yet been performed. In metastatic and recurrent cervical cancer, a number of newer agents, including paclitaxel, gemcitabine, topotecan, and vinorelbine, have demonstrated modest single-agent activity and even greater activity in combination with cisplatin. An expanding series of trials will define the role of these new agents combined with cisplatin and radiation therapy for locally advanced cervical cancer. The potential role of biologic agents in combination with chemoradiotherapy also needs to be examined in locally advanced cervical cancer.
Pathology evaluation of lumpectomy specimen
Authors: C. Perez-Mesa
Journal: JAMA (1991)

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
Die Krankheiten der
Authors: O. Peter Schumacher
Journal: JAMA (1968)

This textbook is an excellent source of thorough information concerning the thyroid. Of special interest to the American reader are the sections summarizing the literature on particular problems—eg, a table of the average weights of the thyroid glands in both males and females, presented by age from 1 month to 70 years; or the comprehensive tabular summary of the effectiveness of thyroxine and the many synthetic thyroid analogs, in terms of calorogenic properties, goiter prevention, tadpole metamorphosis, and substitution in myxedema therapy. Also provided are excellent synopses of some controversial issues in thyroid physiology—eg, a summary of the literature on halflife, total extrathyroidal thyroxinespace, and related data focuses on the differences reported by the various authors and demonstrates where the data are well founded. This technique would be useful in other publications, for it summarizes differences of opinion in a meaningful way that would resolve many of the "debates" that
Psychoendocrine Concomitants in Patients following a New Design of a Geriatric Day-Care Unit
Authors: Johan Lökk
Journal: Psychotherapy and Psychosomatics (1998)

&lt;b&gt;Background: &lt;/b&gt;Seventeen nondemented geriatric day-care attendees were subjected to a reorganized rehabilitation programme. It is suggested that increased control of and participation in the rehabilitation process might decrease psychoendocrine stress from uncertainty and passivity. &lt;b&gt;Method: &lt;/b&gt;The new programme was a change from a traditional one-shift day-care into a two-shift design with two different patient sets a day. The programme was more individualized and time-efficient with written short- and long-term goals. Regular multidisciplinary case conferences were held with the patients to follow and feedback the progress of each individual patient. The patients were prospectively followed with stress markers such as prolactin, cortisol, dehydroepiandrosterone (DHA – a testosterone metabolite), estradiol, serum lipids and serum glucose. &lt;b&gt;Results: &lt;/b&gt;There was significant increase in anabolic hormones (DHA, estradiol), which contrasted with a significant decrease in catabolic hormones (prolactin, cortisol) during the actual day-care period. This pattern was restored at the 24-week follow-up for estradiol and prolactin, but with a continuous increase for DHA. Serum lipids and glucose were unaffected. &lt;b&gt;Conclusions: &lt;/b&gt;This study found psychoendocrine changes that might have been elicited by a reorganization of the delivery of health care in elderly and handicapped patients. Further research is needed in order to understand these changes as well as the ideal structure and content of geriatric day-care programmes from a psychophysiological point of view.
Does an association between pesticide use and subsequent declines in catch of Atlantic salmon (Salmo salar) represent a case of endocrine disruption?
Authors: W L Fairchild, E O Swansburg, J T Arsenault, S B Brown
Journal: Environmental Health Perspectives (1999)

Historical aerial applications of the insecticide Matacil 1.8D provide an opportunity to look for potential effects of the endocrine disrupting compound 4-nonylphenol (4-NP) on Atlantic salmon (Salmo salar) populations. Matacil 1.8D contained the carbamate insecticide aminocarb, with 4-NP as primary solvent. Between 1975 and 1985 Matacil 1.8D was applied to forests in Atlantic Canada to control damage from the spruce budworm (Choristoneura fumiferana). After spraying, estimated concentrations of 4-NP in water fell within a range in which estrogenic effects might be anticipated. The spraying coincided with final stages of smolt development in salmon. Salmon catch data were evaluated considering effects on survival of the smolt stage. There was a significant negative relationship between the returns of salmon and the proportion of tributaries sprayed within the Restigouche River drainage basin in 1977. There was also a broader event of unusually heavy salmon smolt mortality in 1977, which contains a significant relationship indicating that where Matacil 1.8D spraying occurred, the smolt mortality increased. For 16 rivers exposed to spraying between 1973 and 1990, a significant proportion (p<0.005) of the lowest salmon catches coincided with Matacil 1.8D spraying. A decline coinciding with the use of Matacil 1.8D was also apparent in blueback herring (Alosa aestivalis) catches in New Brunswick. Because similar relationships were not evident for Matacil 1.8F or fenitrothion, neither of which were formulated with 4-NP, we hypothesize that the 4-NP in Matacil 1.8D was the causal agent. Concentrations of 4-NP described here are within current ranges encountered in industrial effluents and municipal sewage outfalls.