tbuckley/cabot-search huggingface dataset:
Abstract 860: Solution structure of a dGMP fill-in G-quadruplex forms in PDGFR-<i>b</i> promoter
Authors: Kaibo Wang, Jonathan Dickerhoff, Guanhui Wu, Clement Lin, Danzhou Yang
Journal: Cancer Research (2019)

Abstract Platelet-derived growth factor receptor beta (PDGFR-β) is an important cell-surface-receptor tyrosine kinase implicated in PDGF signaling pathways. The PDGFR-β signaling pathway has been demonstrated as an essential component in control of the cellular growth, proliferation, survival, motility and differentiation. Overexpression of PDGFR-β is associated with tumor growth, angiogenesis, and migration, making PDGFR-β an attractive target for anticancer therapeutics. In the PDGFR-β gene promoter, a highly GC-rich proximal promoter region -165 to -139 nt upstream of the transcriptional start site is crucial for basal promoter activity, which can form G-quadruplexes (G4s). These structures can be stabilized by the G4-interactive molecules to inhibit the PDGFR-β transcriptional activity. Our previous structure study showed that the G4 structures formed in the PDGFR-β gene promoter always contain a broken G-strand. The broken-strand structure suggests a possibility of the formation of a G-vacancy-bearing G-quadruplex (GVBQ) structure, which can be complemented and stabilized by guanine and guanine derivatives. Elevated levels of guanine and guanine derivatives/metabolites are found in tumor cells, suggesting that the GVBQs may play important regulatory roles in tumor cell pathological processes, such as PDGFR-β transcriptional regulation. Using NMR, CD, EMSA and DMS footprinting experiments, herein, we contributed the first atomic resolution structure of a dGMP fill-in G4 formed in PDGFR-β gene promoter in potassium solution. Surprisingly, our results showed that solution dGMP preferentially inserts from the 5' end tetrad instead of the G-22 position of the previously determined structure, and maybe in dynamic equilibrium with our previously reported G-quadruplex. The dGMP, like other intramolecular guanines, that forms four Hoogsteen hydrogen bonds with adjacent guanines and stabilizes by electronic coordination with potassium cation as well as the π-π stacking interaction with the middle tetrad guanine. Moreover, a series of guanine derivatives were investigated to fill in this GVBQ, and found that only these derivatives that keep the ability to form Hoogsteen hydrogen bonds in G-tetrad can serve as the substrate, providing insights into designing new guanine derivatives anticancer drugs. Citation Format: Kaibo Wang, Jonathan Dickerhoff, Guanhui Wu, Clement Lin, Danzhou Yang. Solution structure of a dGMP fill-in G-quadruplex forms in PDGFR-b promoter [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 860.
Selective intestinal decontamination with norfloxacin reduces bacterial translocation in ascitic cirrhotic rats exposed to hemorrhagic shock
Authors: J Llovet
Journal: Hepatology (1996)

Bacterial translocation (BT) can be involved in the pathogenesis of severe infections due to bacteria of enteric origin that complicates bleeding cirrhotic patients. To assess the effect of hemorrhagic shock (HS) on the incidence of BT and if selective intestinal decontamination (SID) reduces this incidence, we studied six groups of Sprague-Dawley rats: ascitic rats, ascitic rats exposed to HS with and without previous norfloxacin prophylaxis, healthy rats, and healthy shocked rats with and without previous norfloxacin prophylaxis. BT tended to be higher in ascitic rats with shock than without shock (69% vs. 41%, P = .15) and was significantly higher in healthy rats with than without shock (50 percent vs. 0 percent, P = .01). Norfloxacin significantly reduced translocation in ascitic shocked rats in comparison with nondecontaminated ascitic shocked rats (31 percent vs. 69 percent, P = .038). This effect was due mainly to a reduction of gram-negative BT (O percent vs. 37 percent, P = .008). In addition, norfloxacin prevented translocation in healthy shocked rats. Accordingly, aerobic gram-negative bacteria disappeared from fecal flora in all rats administered norfloxacin, except for Klebsiella species in one control rat. Cecal severe submucosal edema, chronic inflammatory infiltrate, and intestinal lymphangiectasia were significantly more frequent in ascitic rats than in control rats. Intestinal mucosal injury related with HS, particularly subepithelial cecal edema, was observed only in ascitic shocked rats. In conclusion, HS increases the incidence of BT both in ascitic cirrhotic and healthy rats. Norfloxacin reduces significantly the incidence of translocation after shock, especially in those cases caused by aerobic gram-negative bacilli.
Deaths and (Obituaries.
Journal: JAMA (1900)

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
Reversible mesenteric artery stenoses due to methysergide maleate
Authors: R. E. Buenger
Journal: JAMA (1966)

COMPLICATIONS of methysergide maleate therapy for headache have been found to be numerous in both unexplained symptomatology and in a demonstrable form of fibrosis, with its effect on the various structures passing through the involved areas.<sup>1-4</sup>The fibrotic complications have been found by most authors to be a result of, or at least accompanied by, a profound arteritis.<sup>1</sup>Much of the unexplained symptomatology has been attributed to unproven vascular spasm because of the known vasoconstrictive properties of methysergide and the prompt relief of symptoms and observable diminution of circulatory deficiencies (particularly in the extremities) upon withdrawal of the drug.<sup>5-7</sup>The sequence of early arteritis with spasm progressing to irreversible arteritis and regional fibrosis is intriguing, but unproven. That vascular spasm may play a continuing role in late stages of the process is suspected by the usual improvement and frequent recovery from even advanced fibrotic processes if the
THE SCHICK TEST AND IMMUNITY TO DIPHTHERIA
Journal: JAMA (1921)

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
The survival rate in superior sulcus tumors treated by presurgical irradiation
Authors: D. L. Paulson
Journal: JAMA (1966)

Presurgical irradiation in moderate dosage has converted superior sulcus tumors to operable lesions with prolonged survival in some cases. Previous experience was poor whether the patient received no treatment, irradiation alone, or resection followed by irradiation.<sup>7</sup> Bronchogenic carcinomas developing peripherally in the upper lobe of either lung and invading the superior sulcus of the chest (Pancoast's tumor) are usually low-grade epidermoid carcinomas which grow slowly and metastasize late. Situated in the narrow confines of the apex of the chest, they invade early the lymphatics in the endothoracic fascia and involve the lower roots of the brachial plexus, the intercostal nerves, the stellate ganglion, the sympathetic chain, and adjacent ribs and vertebrae, producing severe pain and the Horner's syndrome. Generally such tumors have been considered as not accessible to complete surgical removal and to resist all efforts at irradiation treatment. The average expected time of survival reported in the literature
Death from myocardial infarction after exercise test with normal result
Authors: A. B. Lintgen
Journal: JAMA (1976)

Death from acute myocardial infarction immediately followed a submaximal exercise test with a normal result in a 56-year-old man. Hemorrhage into an intimal atherosclerotic plaque with superimposed, intraluminal clot formation was the cause of coronary artery occlusion. It is probable that the exercise precipitated an intramural capillary rupture and intimal hemorrhage or caused further hemorrhage into a preexisting intimal hematoma. The resulting luminal narrowing and intimal rupture with superimposed clot formation caused coronary artery occlusion. (<i>JAMA</i>235:837-839, 1976)
Commander
Authors: Thomas G. Peters
Journal: JAMA (1988)

Bill and I stood at graveside. My children were there too. For them, this was the first experience of the loss of a friend. Our efforts to save this life had been futile. Biopsies, liver enzyme assays, several operations: each time the patient recovered and for long periods. Then some new intervention was required. Ironically, the very means of the early basis for our relationship had failed: a liver allograft reached end-stage function. Hepatic coma was the end. Bill Gurley and I had begun working together years earlier. He was a PhD candidate studying cyclosporine pharmacology. I was part of a busy multiorgan recovery and transplant service that had developed through clinical and animal laboratory investigative channels. It was early in the cyclosporine experience and no transplant center fully understood the drug's pharmacokinetics. It was very effective in preventing allograft rejection, but could also cause severe renal and hepatic damage.
Pediatric Pathology
Authors: Richard L. Reece
Journal: JAMA (1966)

The second edition of<i>Pediatric Pathology</i>weighs 1 1/3 lb more than its predecessor, stretches for 171 more pages, and, in place of the plain blue cover of 1959, has a latter day Hansel and Gretel outlined against a forest of cartilage columns arising from epiphyseal roots. New syndromes are recorded and fresh interpretations of old diseases set forth. A chapter on chromosomes makes an impressive 26-page debut, and the sections on erythroblastosis and inborn errors of metabolism are expanded. The arrangement of the subject matter is sometimes confusing, eg, all of leukemia hides in the chromosome section, and cystic fibrosis lurks under inborn errors of metabolism; but these distractions are minor if the reader is an alert user of the index. Dr. Stowens, a certified pediatrician as well as a pathologist, rests his book on the bedrock of morphology. A deft codifier of disease, he backs his words with
Cerebral Malaria
Authors: Robert B. Daroff
Journal: JAMA (1967)

During the ten-month period of this study, approximately 1,200 cases of malaria due to<i>Plasmodium falciparum</i>were seen at the 93rd Evacuation Hospital in South Vietnam. Of these, 19 were cases of cerebral malaria that evinced itself after therapy was begun. Although cerebral malaria is often an alarming consequence of<i>P falciparum</i>infection, early recognition and appropriate therapy afford an excellent prognosis.
John Bennett
Authors: S. Bennett
Journal: BMJ (2009)

<h3>Abstract</h3> Neutrophil activation has a pathogenic effect in inflammatory diseases. Protein kinase B (PKB)/Akt regulates diverse cellular responses. However, the significance of Akt in neutrophilic inflammation is still not well understood. Here, we identified 5,7-dimethoxy-1,4-phenanthrenequinone (CLLV-1) as a novel Akt inhibitor. CLLV-1 inhibited respiratory burst, degranulation, and chemotaxis in activated human neutrophils and neutrophil-like differentiated HL-60 (dHL-60) cells. CLLV-1 selectively inhibited Akt phosphorylation in activated human neutrophils and dHL-60 cells. Significantly, CLLV-1 blocked Akt kinase activity and covalently reacted with Akt Cys310 <i>in vitro</i>. The Akt<sub>309-313</sub>peptide-CLLV-1 adducts were determined by NMR or mass spectrometry assay. The level of alkylation agent-conjugated Akt (reduced form) was also inhibited by CLLV-1. Additionally, CLLV-1 ameliorated lipopolysaccharide-induced lung injury and complete Freund’s adjuvant-caused inflammatory arthritis in mice. Together, CLLV-1 acts as covalent-allosteric Akt inhibitor via targeting Akt Cys310 to retrain inflammatory responses in human neutrophils and in inflammatory animals. Our findings provide a mechanistic framework for redox modification of Akt that may be a novel pharmacological target to alleviate neutrophilic inflammation.
A multicenter randomized controlled trial (RCT) of adjuvant chemotherapy (CT) in nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA (EBV DNA) following primary radiotherapy (RT) or chemoradiotherapy (CRT).
Authors: Anthony T. C. Chan, Roger K.C. Ngan, Edwin Pun Hui, Sing Fai Leung, Patricia Poon, VC Sin, Stewart Yuk Tung, Ashley Chi Kin Cheng, Tsz Kok Yau, Victor Lee, Brigette Ma, HC Cheng, Kwok Keung Yuen, Conrad Lee, Michael K. Kam, Stephen Yau, Alice Wan-ying Ng, Frankie Mo, Benny C.Y. Zee, Dennis YM Lo
Journal: Journal of Clinical Oncology (2012)

5511 Background: The benefit of adjuvant CT in NPC is unclear. Administering CT after full-dose CRT presents challenges in treatment compliance and toxicity. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using EBV DNA to select high risk NPC patients (pts) for adjuvant CT while sparing low risk pts from unnecessary toxicity. Methods: Biopsy proven NPC, AJCC stage IIB-IVB, detectable EBV DNA at 6-8 wks post-RT, no persistent locoregional disease or distant metastasis, ECOG 0 or 1, adequate organ function. Randomised with stratification for primary therapy (RT Vs CRT) and tumor stage (II/III Vs IV) to arm A (adjuvant cisplatin 40 mg/m2 and gemcitabine 1000mg/m2, both given on D1+8 q3w x 6 cycles) or arm B (clinical follow-up). EBV DNA and PET scan were performed before and 6 months after randomization. Primary endpoint was relapse free survival and secondary endpoints included toxicity of adjuvant CT. With a hazard ratio of 2, 100 pts were required with a power of 0.8 and an alpha at 0.05. This safety analysis was approved by DMSC. Results: From 9/2006 to 12/2011, 514 pts consented for EBV DNA screening, 95 with detectable EBV DNA consented for adjuvant study. After work-up, 74 were eligible for randomization (37 to arm A; 37 to arm B). The two arms were well balanced in baseline characteristics. 80% received prior neoadjuvant and/or concurrent CT. Staging: IIB (36.5%), III (29.7%), IVA (18.9%), IVB (14.8%). Five pts refused adjuvant CT after randomization. Overall 65% and 57% completed 5 and 6 cycles respectively. Mean dose intensity (DI): 84% for cisplatin (22.5 mg/m2/wk, range 0.0-26.7), 92% for gemcitabine (612.8 mg/m2/wk, range 333.3-777.8). Treatment related adverse events above CTC G2 were summarized in Table. Conclusions: Delivery of 6 cycles of adjuvant CT is feasible with acceptable toxicity after full dose RT or CRT. [Table: see text]
The changing rate of major depression. Cross-national comparisons. Cross-National Collaborative Group
Journal: JAMA (1992)

<h3>Objective.</h3> —To estimate temporal trends in the rates of major depression cross-nationally. <h3>Design.</h3> —Nine epidemiologic surveys and three family studies. <h3>Setting and Participants.</h3> —Approximately 39 000 subjects in population-based samples from nine epidemiologic surveys, and 4000 relatives from three family studies that were conducted independently but using similar methodology in the 1980s in North America, Puerto Rico, Western Europe, the Middle East, Asia, and the Pacific Rim. <h3>Outcome Measures.</h3> —Age at first onset of major depression by birth cohort and time period. <h3>Results.</h3> —There was an increase in the cumulative lifetime rates of major depression with each successively younger birth cohort at all sites with the exception of the Hispanic samples, in whom the rates in the older cohort (1915 through 1935) were approximately equal to those of the younger cohorts. However, results of fitting statistical models that separate period and cohort effects showed an overall increase in the rates of major depression over time over all countries, although the magnitude of the increase varied by country. The average relative risk of major depression between a particular cohort and the cohort born immediately before varied between 2.6 (95% confidence interval, 1.8 to 3.7) in Florence, Italy, and 1.3 (95% confidence interval, 1.2 to 1.4) in Christchurch, New Zealand. Short-term fluctuations in the rates of major depression during specific time periods and in specific cohorts also varied by country. <h3>Conclusions.</h3> —Cross-nationally, the more recent birth cohorts are at increased risk for major depression. There are, however, variations in the long- and short-term trends for major depression by country, which suggests that the rates in these countries may have been affected by differing historical, social, economic, or biological environmental events. The linking of demographic, epidemiologic, economic, and social indices by country to these changes may clarify environmental conditions that influence the rates of major depression. (<i>JAMA</i>. 1992;268:3098-3105)
Sperm, a Source of Estrogen
Authors: Rex A. Hess, David Bunick, Janice M. Bahr
Journal: Environmental Health Perspectives (1995)

This review article discusses a novel nontraditional site of estrogen synthesis and the potential targets of estrogen action within the male reproductive system.Our laboratories have recently demonstrated that developing spermatids in several species contain aromatase, the cytochrome P450 enzyme responsible for converting androgens into estrogens.The enzyme was localized by immunocytochemistry and the protein's presence was confirmed by Western blot analysis.Northern blot analysis and in situ hybridization were used to corroborate the presence of mRNA for aromatase.It appears that the aromatase message precedes the synthesis of the protein, and the protein remains in the spermatids several days after the message disappears.The enzyme is located along the tail of newly released sperm and is active in the epididymal sperm as well as in the developing germ cells of the testis.This unique discovery is the basis for our overall hypothesis that estrogen, synthesized by sperm, plays a role in the regulation of epididymal function proportional to the number of sperm being transported.The presence of an estrogen source within the ductal lumen is of special importance to the study of epididymal function because the regulatory mechanisms in this region remain unclear, particularly for the efferent ductules and initial segment regions, although estrogen receptors have been identified in the ductal epithelium.An understanding of the role that estrogen plays in the function of the epididymis may provide benefits in several areas including the treatment of abnormalities in epididymal function, the potential development of a male contraceptive, and insight into the causes of adult epididymal lesions induced by neonatal exposure to estrogenic compounds such as diethylstilbestrol.
Rapid Assessment of Vectorborne Diseases During the Midwest Flood—United States, 1993
Journal: JAMA (1994)

Heavy spring and summer rainfall during 1993 caused the most extensive flash and riverine flooding ever recorded in the upper midwestern United States. In portions of the flood region,* standing water provided large expanses of habitat capable of producing large populations of the mosquitoes Culex pipiens and Cx. tarsalis. These species can rapidly amplify transmission of the arboviruses that cause St. Louis encephalitis (SLE) and western equine encephalitis (WEE). Although information from state health departments in the disaster area indicated minimal SLE or WEE activity in the region before the flooding, large vector populations in certain areas following the flooding increased the potential for exposure of residents and emergency workers to arboviral infection. To determine the risk for arboviral disease in the disaster area, CDC, in collaboration with state and local health departments, conducted surveillance during August-September 1993. This report summarizes the results of the surveillance activity.
American Journal of Geriatric Psychiatry
Authors: Virginia M. Bowden
Journal: JAMA (1995)

The<i>American Journal of Geriatric Psychiatry</i>serves as the official journal of the American Association for Geriatric Psychiatry, an organization with approximately 1500 members. In the inaugural issue, the editor describes plans to make available the latest scientific and clinical developments relating to aging and mental health by publishing original research results, scholarly review articles, and clinical reports. This journal contains a diverse selection of special articles, regular articles, clinical and research reports, editorial commentaries, and book reviews. A sampling of topics with a clinical focus includes geriatric depression, somatization disorder, geriatric psychopharmacology, and consultation in nursing homes. Other areas addressed are ethical and legal concerns, public policy, and academic interests. The "Special Articles" section provides a comprehensive review of the literature in clinically pertinent subject areas. It gives special emphasis to theory, conceptual understanding, data, and recent research findings. In the first issue the flow of this information is