tbuckley/cabot-search huggingface dataset:
Abstract 1497: Differential Modulation of Endothelial Nitric Oxide Synthase (eNOS) Signaling Pathways by Tetrahydrobiopterin Synthesis vs. Salvage
Authors: Toru Sugiyama, Ruqin Kou, Thomas Michel
Journal: Circulation (2007)

Tetrahydrobiopterin (BH4) is an essential redox-active cofactor for eNOS that can be both synthesized de novo or salvaged by enzymatic reduction of the oxidized compound. The endothelial dysfunction associated with diabetes is accompanied a decrease in the abundance of bioactive BH4. De novo biosynthesis of BH4 is catalyzed by GTP cyclohydrolase-1 (GTPCH1); recycling of BH4 is catalyzed by dihydrofolate reductase (DHFR). The relative roles of de novo BH4 synthesis and BH4 redox recycling in regulation of eNOS bioactivity remain incompletely defined. In the present study, we have used siRNA methods to investigate the effects of BH4 “knockdown” on eNOS regulation and endothelial signal transduction pathways in bovine aortic endothelial cells. We transfected duplex siRNA constructs designed to specifically target DHFR and GTPCH1, and suppressed levels of these proteins by ~90% (n = 37) relative to control siRNA-transfected cells. Transfection of siRNA constructs targeting DHFR or GTPCH1 suppressed VEGF-induced eNOS activity (using [ 3 H]-citrulline assay) or NO production (using an electrochemical NO sensor) by 90 ± 9% (n = 8, p &lt; 0.01). siRNA-mediated knockdown of either DHFR or GTPCH1 had no effect on the abundance of stability of eNOS dimers, assessed using low-temperature SDS-PAGE (n = 4). DHFR knockdown completely blocked VEGF-induced eNOS dephosphorylation at the inhibitory phosphoserine residue 116 (n = 4, p &lt; 0.01), but had no effect on agonist-modulated eNOS phosphorylation at the activating phosphoserine residue 1179. GTPCH1 knockdown had no effect either on phosphorylation or dephosphorylation of eNOS at these residues. Phosphorylation of Akt was decreased by 85 ± 4% by DHFR knockdown (p &lt; 0.001, n = 4) but Akt phosphorylation was unaffected by GTPCH1 knockdown. These studies demonstrate for the first time a striking contrast in the consequences for eNOS signaling pathways from the suppression of BH4 salvage/reduction vs. de novo BH4 synthetic pathways. The abrogation of VEGF-mediated Akt activation by siRNA-mediated DHFR knockdown indicates that alterations in BH4 recycling may have broad effects on cell signaling pathways, with important consequences for the development of endothelial dysfunction in vascular disease states.
Proctology
Authors: E. Parker Hayden
Journal: New England Journal of Medicine (1950)

Unusual Proctologic CasesBurt17 reports an unusual occurrence in the case of a woman in whom he had excised a presumed blind fistulous tract extending upward from the mucocutaneous junction in the left anterior quadrant of the rectal wall. This woman had had pain in this area for a year prior to operation and had also had two previous injections of oil into some internal hemorrhoids.At operation an area of tissue 6 by 4 by 2 cm. was excised, including the linear area of induration thought to be a fistulous tract. Two days later the patient had a temperature . . .
Fetal Hemoglobin In Sickle Cell Anemia: Molecular Characterization of Saudi Patients From the Southwestern Province.
Authors: Abdulrahman Alsultan, Nadia Solovieff, Aamer Aleem, Farjah H. AlGahtani, Ali Al-Shehri, Mohamed Elfaki Osman, Kadijah Kurban, Hasan Bahakim, Abdul Kareem Al-Momen, David H.K. Chui, Martin H. Steinberg
Journal: Blood (2010)
Transplantation, Baltimore
Journal: JAMA (1970)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Risk factors for heatstroke. A case-control study
Authors: E. M. Kilbourne
Journal: JAMA (1982)

To identify risk factors associated with heatstroke, a case-control study in St Louis and Kansas City, Mo, was conducted during July and August 1980. Questionnaire data were gathered for 156 persons with heatstroke (severe heat illness with documented hyperthermia) and 462 control subjects matched by age, sex, and neighborhood of residence. A stepwise linear logistic regression procedure was used to identify factors significantly associated with heatstroke. Alcoholism, living on the higher floors of multistory buildings, and using major tranquilizers (phenothiazines, butyrophenones, or thioxanthenes) were factors associated with increased risk. Factors associated with decreased risk were using home air conditioning, spending more time in air-conditioned places, and living in a residence well shaded by trees and shrubs. Being able to care for oneself, characteristically undertaking vigorous physical activity, but reducing such activity during the heat, and taking extra liquid were also associated with decreased risk. Our findings also suggest effective preventive measures. During a heat wave, the greatest attention should be directed toward high-risk groups, and relief efforts should include measures shown to be associated with reduced risk. (<i>JAMA</i>1982;247:3332-3336)
Letter: Charles A. Lindbergh: medical scientist
Authors: A. Meltzer
Journal: JAMA (1976)

<h3>To the Editor:—</h3> One of Burrows' main points is that clinical errors uncovered by autopsy were of "academic interest only, either because the patients had terminal conditions on admission or because the therapy available would not have appreciably altered their clinical course." Are we to interpret this to mean that if patients are going to die anyway, or if available therapy will not help their disease, then there is no point in knowing what was wrong with them? Further along, he states that "numerous minor autopsy diagnoses such as gallstones and adenomas of the thyroid and adrenal glands provide additional data for statistics but are often of very limited clinical value." Does this mean that we are to indict the autopsy because pathologists have not been able to decipher the significance of adrenal adenomas? In addition to the philosophical objections, I must also protest that Burrows has not provided evidence
Staging of breast cancer and survival rates. An assessment based on 50 years of experience with radical mastectomy
Authors: D. J. Ferguson
Journal: JAMA (1982)

The correlation of staging criteria for mammary carcinoma with the curability of primary and recurrent local and regional lesions was assessed by follow-up after 1,259 consecutive radical mastectomies performed in women under age 70 between 1927 and 1978. Using a staging scheme revised in the light of our experience, the incidence of recurrence by 20 years was 34% ±2.7% for pathological stage I, 65% ±2.6% for stage II, and 83% ±2.5% for stage III. Recurrence after 20 years was observed in one of 178 patients. After treatment of local recurrence, three of 51 patients survived 20 years. By restriction of entry into clinical or pathological stages I and II, currently employed revisions of staging criteria appear to increase survival in all stages, while placing patients with possibly curable lesions in stages III and IV. (<i>JAMA</i>1982;248:1337-1341)
Empowerment of liver cancer patients for an improved management of post-embolization syndrome: impact of a nurses educational program
Authors: Neus Llarch, Gemma Iserte, Víctor Sapena, Marco Sanduzzi Zamparelli, Sergio Muñoz Martinez, Marta Burrel, Marta Barrufet, Patricia Bermudez, Anna Darnell, Alejandro Forner, Jordi Bruix, María Reig
Journal: Journal of Hepatology (2020)
TMOD-08A MOUSE MODEL OF YOUNG ADULT GLIOBLASTOMA: IN VIVO EXPRESSION OF MUTATED IDH1 (R132H) GENE USING THE SLEEPING BEAUTY TRANSPOSASE SYSTEM
Authors: Felipe J. Nunez, Flor Mendez, Carl Koshmann, Alexandra Calinescu, Marta Dzaman, Pedro Lowenstein, Maria Castro
Journal: Neuro-Oncology (2015)
The orthopaedic training study
Authors: G. E. Miller
Journal: JAMA (1968)

The Orthopaedic Training Study, a joint enterprise of the American Board of Orthopaedic Surgery and the Center for the Study of Medical Education of the University of Illinois, is now four years old. As a new phase is about to be undertaken, it seems fitting to describe to the medical profession at large what has been accomplished in this critical examination of one facet of graduate medical education, as well as what is proposed. In the interest of perspective, it is useful to begin with a reminder that the study was launched to explore a set of issues about efficiency in the use of limited manpower resources, issues which were serious in 1963 but have reached critical dimensions in 1968. The facts are simple. More man years are now devoted to postdoctoral than to predoctoral professional education in medicine. These years are under the control of specialty boards whose distinguished
Caustic burns from contact with wet cement
Authors: S. H. Early
Journal: JAMA (1985)

Cement is a widely used mixture in construction. A corrosive alkali, calcium hydroxide, is liberated as water is added to the lime present in the cement mixture. Skin contact for prolonged periods produces deep chemical burns with thick eschar formation. Five cases of chemical burns to the lower extremities following contact with the cement mixture are presented. When full-thickness burns were present, long periods of hospitalization were necessary for eschar separation prior to skin grafting. Early excision of full-thickness caustic burns with immediate skin grafting diminished the length of hospitalization and returned the patient to work sooner. (<i>JAMA</i>1985;254:528-529)
Vaccination Coverage by Race/Ethnicity and Poverty Level Among Children Aged 19-35 Months—United States, 1996
Journal: JAMA (1997)

The Childhood Immunization Initiative (CII), implemented in 1993, is an intensive program to increase vaccination coverage among preschool-aged children and to reduce or eliminate vaccine-preventable diseases. In 1996, national coverage goals were achieved for 2-year-old children for the most critical doses of each routinely recommended vaccine. Disparities in vaccination coverage have been documented previously among different racial/ethnic groups. This report presents findings from CDC's National Immunization Survey (NIS), which document progress toward achieving the 1996 CII vaccination coverage goals by racial/ethnic group and by level of poverty. The findings indicate that, for each of five racial/ethnic groups, most of the national CII vaccination coverage goals were met and that, based on poverty level, all the goals were met for children living at or above the poverty level, and two of the five goals were met for children living below the poverty level.
A Preliminary Report on the Treatment of Interstitial Keratitis.
Journal: JAMA (1925)

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
WHAT CONSTITUTES THE PRACTICE OF MEDICINE?
Journal: JAMA (2008)

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
Small-bowel endoscopy
Authors: M. Pennazio
Journal: Endoscopy (2010)

The past decade has seen a revolution in small-bowel endoscopy. The significant advance in diagnostic ability introduced by capsule endoscopy has prompted interest in further improvements in diagnostic capability, as well as new methods to treat the lesions identified. Capsule endoscopy was quickly followed by double-balloon enteroscopy (DBE), which offered new therapeutic options. Technical progress has continued to be rapid, such that we now have the so-called device-assisted enteroscopy (DAE), which includes DBE, single-balloon enteroscopy (SBE), and spiral enteroscopy, through which diagnostic and therapeutic interventions are available.
(Ex?) Dementia Pugilistica in Ex-Boxers
Journal: JAMA (1969)

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
CHAIRMAN'S ADDRESS.
Authors: G. V. WOOLEN
Journal: JAMA (1896)

<h3>Gentlemen of the Section:</h3> —It is especially pleasing to me to meet so many of you again, and in this fair city of the South already noted for its activity in promoting the general welfare of mankind. I again wish to express to you my sincere thanks for the high honor conferred in selecting me to preside over this part of our work so dear to us all. Whatever may be our ideas relative to specialties and the organization of special societies, it must be conceded that the unity of the profession must be preserved, and that much of our best work should be performed in connection with the meetings of thisAssociation. It is, therefore, fitting that we meet annually with the profession for special as well as general work, and the consideration of matters pertaining to the general welfare of the fraternity. It will be a sad day
Hand Function
Journal: JAMA (2001)

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
Clinical evaluation of cisplatin sensitivity germ line polymorphisms in neoadjuvant chemotherapy (NAC) for urothelial cancer (UC).
Authors: Peter H. O'Donnell, Ilana Rebecca Garcia-Grossman, Hongyuan Cao, Irina Ostrovnaya, Elizabeth R. Plimack, Kelly Lynn Stratton, Christopher Manschreck, Norm D. Smith, Gary D. Steinberg, Vijai Joseph, Kenneth Offit, Walter Michael Stadler, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2014)

342 Background: Cisplatin-based NAC in UC confers a survival benefit, but prediction of which patients (pts) will benefit is not possible. We attempted to validate pharmacogenomic (PGx) markers of cisplatin sensitivity derived from a cell-based model and previously associated with response in a population of pts receiving NAC. Methods: Three germline single nucleotide polymorphisms (SNPs) were previously associated with pathologic response at cystectomy in a single-institution discovery set of 59 cT2 UC pts. These SNPs were tested for association with NAC response in a prospectively-identified, multi-institution, independent cohort. The primary analysis tested for association between rs244898 and rs7937567 and pathologic complete response (pT0). A replication set of 134 pts would provide 80% power to detect effects of both SNPs at p=0.05 independently using a multivariate logistic model. Results: N=146 pts with ≥cT2 N0 disease were identified from three institutions. All pts received ≥3 cycles of cisplatin-based NAC and underwent definitive surgery. Rates of pT0 and &lt;pT2 were 26% and 50%, respectively, comparable to the discovery population. Though each SNP had a &gt;5 odds ratio of effect on pT0 in the discovery set, neither was associated with achievement of pT0 in the replication set. The third SNP (rs10964552) which was associated with pathologic downstaging in the discovery set, also failed to replicate. All three SNPs were in Hardy-Weinberg equilibrium, and minor allele frequencies were similar between discovery and validation. Conclusions: Three germline SNPs previously associated with platinum sensitivity in pre-clinical and clinical models were not associated with NAC response in a large replication cohort of UC pts. Reasons for failure may include unmeasured clinical differences between the pt cohorts, a higher proportion of MVAC use in the replication set compared to gemcitabine/cisplatin in discovery pts, or simply spurious association in the discovery cohort. These results emphasize the need for replication when evaluating PGx markers, and demonstrate that multi-institutional efforts are feasible and will likely be necessary to achieve advances in UC PGx.
Abstract 4670: The molecular mechanisms of EpCAM in regulating tumor progression in colon cancer cells
Authors: Kang-Hao Liang, Hsien-Cheng Tso, Shao-Hsi Hung, Mei-Ying Liao, Han-Chung Wu
Journal: Cancer Research (2019)

Abstract Epithelial cell adhesion molecule (EpCAM) is highly expressed in advanced epithelial cancers and tumor-initiating cells, but its role in cancer progression remains to be elucidated. Here, we show that the extracellular domain of EpCAM (EpEX) acts through its EGF-like domain I to bind EGFR and activates downstream ERK1/2 and AKT signaling. Inhibition or shRNA knockdown of EGFR ablated EpEX-induced ERK1/2 and AKT phosphorylation in colon cancer cells. EGFR signaling, stimulated by either EpEX or EGF, then induces regulated intramembrane proteolysis of EpCAM, releasing both EpEX and EpCAM intracellular domain (EpICD). MEK inhibitor, U0126, prevented EpEX-induced EpCAM proteolysis by ADAM17 and presenilin 2 proteases. Furthermore, EGFR inhibitor, AG1478, and MEK inhibitor, U0126, both decreased the production of EpICD, which was found to be necessary for nuclear accumulation of β-catenin protein and expression of HIF1α target genes in vitro and in mouse xenograft models. In clinical samples from colorectal carcinoma patients, high levels of nuclear EpICD predicted metastasis and poor prognosis. Importantly, we also showed that EpAb2-6, an anti-EpCAM neutralizing monoclonal antibody, inhibited EpEX-activated EGFR-PI3K-AKT signaling and induced apoptotic signaling through FOXO3a activation of HTRA2 gene expression. This antibody also inhibited the nuclear translocation of EpICD and oncogenic signaling through β-catenin. Finally, in both metastatic and orthotopic animal models of colorectal cancer, EpAb2-6 therapy exhibited an antitumor effect and markedly extended the survival time of mice. Taken together, the results demonstrate that EpEX contributes to malignancy by functioning as a growth factor, which activates EpICD-mediated signaling, thereby enhancing colon cancer cell survival. Furthermore, the data indicate that EpEX can be considered as a promising target for treatment of colon cancer. Citation Format: Kang-Hao Liang, Hsien-Cheng Tso, Shao-Hsi Hung, Mei-Ying Liao, Han-Chung Wu. The molecular mechanisms of EpCAM in regulating tumor progression in colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4670.