tbuckley/cabot-search huggingface dataset:
Abstract 864: Novel synthetic berbamine derivatives inhibit Jak2/Stat3 signaling and induce apoptosis of human melanoma cells
Authors: Sangkil Nam, Jun Xie, Angela Perkins, Yuelong Ma, Fan Yang, Jun Wu, Yan Wang, Rong-zhen Xu, Wendong Huang, David A. Horne, Richard Jove
Journal: Cancer Research (2012)

Abstract Persistent Jak/Stat3 signal transduction plays a crucial role in tumorigenesis and immune development. Activated Jak/Stat3 signaling has been validated as a promising molecular target for cancer therapeutics discovery and development. Berbamine (BBM), a natural bis-benzylisoquinoline alkaloid, was identified from the traditional Chinese herbal medicine Berberis amurensis used for treatment of cancer patients. While BBM has been shown to have potent antitumor activities with low toxicity in various cancer types, the molecular mechanism of action of BBM remains largely unknown. Here, we determine the antitumor activities of thirteen synthetic berbamine derivatives (BBMDs) against human solid tumor cells. BBMD3, which is the most potent in this series of novel BBMDs, exhibits over 6-fold increase in biological activity compared to natural BBM. Moreover, BBMD3, directly inhibits Jak2 autophosphorylation kinase activity in vitro with IC50 = 0.69 μM. Autophosphorylation of Jak2 kinase at Tyr1007/1008 sites also was strongly inhibited in the range of 1 μM to 5 μM of BBMD3 in human melanoma cells 4 h after treatment. Following inhibition of autophosphorylation of Jak2, BBMD3 blocked constitutive activation of downstream Stat3 signaling in melanoma cells. BBMD3 also down-regulated expression of Stat3 target proteins Mcl-1and Bcl-xL, associated with induction of apoptosis. In sum, our findings demonstrate that the novel berbamine derivative BBMD3 is an inhibitor of the Jak2/Stat3 signaling pathway, suggesting evidence for a molecular mechanism whereby BBMD3 exerts at least part of apoptosis of human melanoma cells. In addition, BBMD3 represents a promising lead compound for development of new therapeutics for cancer treatment. 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 864. doi:1538-7445.AM2012-864
Recurrent Loss of Sex Is Associated with Accumulation of Deleterious Mutations in Oenothera
Authors: Jesse D. Hollister, Stephan Greiner, Wei Wang, Jun Wang, Yong Zhang, Gane Ka-Shu Wong, Stephen I. Wright, Marc T.J. Johnson
Journal: Molecular Biology and Evolution (2014)

Sexual reproduction is nearly universal among eukaryotes. Theory predicts that the rarity of asexual eukaryotic species is in part caused by accumulation of deleterious mutations and heightened extinction risk associated with suppressed recombination and segregation in asexual species. We tested this prediction with a large data set of 62 transcriptomes from 29 species in the plant genus Oenothera, spanning ten independent transitions between sexual and a functionally asexual genetic system called permanent translocation heterozygosity. Illumina short-read sequencing and de novo transcript assembly yielded an average of 16.4 Mb of sequence per individual. Here, we show that functionally asexual species accumulate more deleterious mutations than sexual species using both population genomic and phylogenetic analysis. At an individual level, asexual species exhibited 1.8× higher heterozygosity than sexual species. Within species, we detected a higher proportion of nonsynonymous polymorphism relative to synonymous variation within asexual compared with sexual species, indicating reduced efficacy of purifying selection. Asexual species also exhibited a greater proportion of transcripts with premature stop codons. The increased proportion of nonsynonymous mutations was also positively correlated with divergence time between sexual and asexual species, consistent with Muller's ratchet. Between species, we detected repeated increases in the ratio of nonsynonymous to synonymous divergence in asexual species compared with sexually reproducing sister taxa, indicating increased accumulation of deleterious mutations. These results confirm that an important advantage of sex is that it facilitates selection against deleterious alleles, which might help to explain the dearth of extant asexual species.
TCT-36 Prognostic Difference of Normal Versus High Presenting Blood Pressure in Patients With Acute ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Donghun Shin, Kwang Soo Cha, Jun-Hyok Oh, Dae-sung Lee, Hye Won Lee, Jung Hyun Choi, Han Cheol Lee, Taek Jong Hong
Journal: Journal of the American College of Cardiology (2014)
Infarction of Breast Fibroadenomas During Pregnancy
Authors: Bhagirath Majmudar
Journal: JAMA (1975)

Two cases of infarcted fibroadenomas of the breast during pregnancy represent the total incidence of this entity from a total of 404 fibroadenomas diagnosed during the last five years in our department. Gross and microscopic pathologic findings of these breast tumors must be carefully evaluated, since the relative rarity of this lesion may lead to suspicion of carcinoma.
177 EVALUATION OF PHYSICIAN AGREEMENT FOR DEFINING “CLINICAL SUSPICION OF REJECTION” IN LIVER TRANSPLANTATION
Authors: M. Rodríguez-Perálvarez, G. Germani, B. Hogan, A. Poyato- González, J. O'Beirne, M. Senzolo, J.L. Montero-Álvarez, D. Patch, A.P. Dhillon, P. Burra, M. De la Mata, A.K. Burroughs
Journal: Journal of Hepatology (2013)
THE ESTIMATION OF PROTEIN IN URINE AND ITS RELATION TO CASTS
Authors: F. T. Grey
Journal: BMJ (1930)

The patienit was readmitted in August., 1928, as a surgical emer- gency, with pains of a severe griping character, irrespective of viseus.This remainedl inl a quiescent state until August, 1928, her seconld admissionl, whenl the stonle ulcerated thrlough the gall-blailder into the alimentary tract.It is well knlowni that an impacted gall-stone may ulcerate either into tlle colon or the duiodenum.In this case, however, it would appear that thiere is a connexion between all three viscera- namllely, tlho biliary passages, duodenum, and transvelrso coloin.The possible explanationis are three:
Studies on Some Factors Influencing Anemia in Tumor-Bearing Animals
Authors: Earl G. Yonehiro
Journal: JAMA (1963)

THE RELATIONSHIP OF ANEMIA and cancer has been a challenging problem for many years and has been reviewed in an excellent monograph by Price and Greenfield.1in 1951, Shen and Homburger2found that in only 33 of 113 anemic cancer patients could the anemia be explained completely on the basis of hemorrhage or blood loss. Moreover, in only 48 patients could the anemia be explained even partially on this basis. They concluded that no correlation could be established between the extent of metastasis and the degree of anemia.  Taylor and Pollack3published evidence based on 155 tumor-implanted mice, which indicated that tumor tissue had an antagonistic effect on the blood hemoglobin of the host; the hemoglobin level was depressed by the time the tumor implants had grown to measurable size and became progressively lower until the death of the animal. These authors postulated an adverse action
ABC of clinical genetics. Special issues.
Authors: H. M. Kingston
Journal: BMJ (1989)

Various issues that arise during genetic counselling need special consideration and are briefly reviewed in this chapter.Consanguinity or disputed paternity affect the assessment of genetic risk, and families with genetic disorders need to know about adoption and other reproductive options.The study of twins has proved valuable in determining the genetic contribution to the aetiology of many disorders.In some genetic conditions population screening may be appropriate in the prevention or early detection of disease.The overall approach to genetic disorders raises various important ethical issues, which need to be faced by the family, the medical profession, and society.m m Denote different disorders Autosomal recessive disorders in a family with complex consanguinity. Consanguinity Degree of genetic relationshipFirst: * Existing child with autosomal recessive disorder * Husband has autosomal dominant disorder * Husband has chromosomal abnormality leading to infertility or recurrent spontaneous abortion Ovum donation * Wife has autosomal dominant or X linked disorder * Wife has chromosomal abnormality leading to infertility or recurrent spontaneous abortion Contraception * Couples waiting for new medical developments Sterilisation * Couples whose family is complete Twins
Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-β
Authors: Hanning You, Wei Ding, Bart C. Rountree
Journal: Hepatology (2010)

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. CD133, a transmembrane glycoprotein, is an important cell surface marker for both stem cells and cancer stem cells in various tissues including liver. CD133 expression has been recently linked to poor prognosis in HCC patients. CD133+ liver cancer cells are characterized by resistance to chemotherapy, self-renewal, multilineage potential, increased colony formation, and in vivo cancer initiation at limited dilution. Recent studies demonstrate that CD133 expression is regulated by DNA methylation. In this study, we explored the role of transforming growth factor β (TGFβ), a multifunctional cytokine that plays a critical role in chronic liver injury, in the regulation of CD133 expression. TGFβ1 is capable of up-regulating CD133 expression specifically within the Huh7 HCC cell line in a time- and dose-dependent manner. Most important, TGFβ1-induced CD133+ Huh7 cells demonstrate increased tumor initiation in vivo . Forced expression of inhibitory Smads, including Smad6 and Smad7, attenuated TGFβ1-induced CD133 expression. Within CD133− Huh7 cells, TGFβ1 stimulation inhibited the expression of DNA methyltransferases (DNMT) 1 and DNMT3β, which are critical in the maintenance of regional DNA methylation, and global DNMT activity in CD133− Huh7 cells was inhibited by TGFβ1. DNMT3β inhibition by TGFβ1 was partially rescued with overexpression of inhibitory Smads. Lastly, TGFβ1 treatment led to significant demethylation in CD133 promoter-1 in CD133− Huh7 cells. Conclusion: TGFβ1 is able to regulate CD133 expression through inhibition of DNMT1 and DNMT3β expression and subsequent demethylation of promoter-1. TGFβ1-induced CD133+ Huh7 cells are tumorigenic. The mechanism by which TGFβ induces CD133 expression is partially dependent on the Smads pathway. Hepatology 2010
Persistent Vomiting of Bile In a Premature Infant
Authors: Wilbur L. Smith
Journal: JAMA (1975)

<h3>History</h3> A 12-hour-old premature infant was first seen with persistent bilious vomiting. He had not yet been fed and had passed meconium ten hours after birth. On physical examination, he was found to have peculiar facies and upper abdominal distention. Figures 1 and 2 were obtained as part of the diagnostic evaluation. <h3>Diagnosis</h3> Duodenal atresia. <h3>Comment</h3> Figures 1 and 2 show two air-filled upper abdominal structures representing the very dilated stomach and duodenal bulb. The remainder of the alimentary tract was gasless. This combination of findings suggested congenital duodenal obstruction. Further inspection of Fig 1 disclosed an unusual configuration of the pelvis. The superior margins of the acetabula were flat and the ilia were flared. These findings suggested Down syndrome (trisomy 21), a condition commonly associated with duodenal atresia. Duodenal obstruction accounts for about 25% of all cases of alimentary tract obstruction in newborns. It occurs in about 1 in
389 LONG-TERM EVALUATION OF FIBROSIS BY TRANSIENT ELASTOGRAPHY IN PATIENTS CLEARING HCV ON ANTIVIRAL THERAPY
Authors: V. Calvaruso, P.L. Almasio, P. Pizzillo, R. Di Stefano, V. Di Marco, C. Cottone, S. Petta, A. Calì, A. Craxì
Journal: Journal of Hepatology (2010)
REMOVAL OF GALL BLADDER IN A WOMAN AGED 75
Authors: A. W. Addinsell
Journal: BMJ (1905)

Since these remarks were written, another case showing the benefit of short-circuiting for carcinoma of transverse colon has reappeared at hospital.I " short-circuited " more than two years ago, and on recovery proposed excision of the can- cerous colon.But the poor fellow, aged 31, was obliged to decline, as his business matterq were in confusion and required his personal attention then.He only returned three weeks ago looking very well and with regular bowels, but the growth was too far gone to justify removal (vide Clin.8
Coadministration of Liraglutide With Tacrolimus in Kidney Transplant Recipients: A Case Series
Authors: Nicole R. Pinelli, Anita Patel, Francine D. Salinitri
Journal: Diabetes Care (2013)

Glucocorticoids commonly used in the posttransplant period have been demonstrated to reduce insulin sensitivity, impair α-cell function, and more recently, impair β-cell function and the incretin effect (1). Liraglutide is an incretin mimetic approved for the treatment of type 2 diabetes. One major concern about the use of liraglutide after transplantation is that it delays gastric emptying, which could potentially affect absorption of coadministered oral medications, such as tacrolimus, which has a narrow therapeutic index (2). This case series is the first to report on the safety of this drug combination in kidney transplant recipients (KTRs).

Nonpregnant, adult (≥18 years of age), and clinically stable (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 and not experiencing allograft rejection or two serum creatinine values >30% of each other obtained at least 1 week apart within 4 weeks prior to enrollment) KTRs receiving unchanged tacrolimus doses for ≥4 weeks (goal trough concentration 5–15 …
Use of bronchoalveolar lavage in the evaluation of methotrexate lung disease.
Authors: G M Akoun, C M Mayaud, J L Touboul, M F Denis, B J Milleron, J Y Perrot
Journal: Thorax (1987)

The results of bronchoalveolar lavage in three patients with a presumptive diagnosis of methotrexate induced lung disease are presented. Lavage fluid was characterised by the presence of large numbers of lymphocytes, which in two patients were predominantly lymphocytes of the T8 phenotype. These findings further support the hypothesis that immune mediated mechanisms may play a part in the pathogenesis of this disorder in some patients, and indicate that bronchoalveolar lavage may be helpful in the evaluation of patients suspected of having methotrexate induced lung disease.
In utero pulmonary artery and aortic growth and potential for progression of pulmonary outflow tract obstruction in tetralogy of fallot
Authors: Lisa K. Hornberger, Stephen P. Sanders, David J. Sahn, Mary Jo Rice, Philip J. Spevak, Beryl R. Benacerraf, Robert W. Mcdonald, Steven D. Colan
Journal: Journal of the American College of Cardiology (1995)
Adenovirus Encoding Human Platelet-Derived Growth Factor-B Delivered in Collagen Exhibits Safety, Biodistribution, and Immunogenicity Profiles Favorable for Clinical Use
Authors: Dan-ling Gu, Thanh Nguyen, Ana Maria Gonzalez, Marie A Printz, Glenn F Pierce, Barbara A Sosnowski, M.Laurie Phillips, Lois A Chandler
Journal: Molecular Therapy (2004)

We have developed a therapeutic approach to wound repair involving immobilization of gene transfer vectors within biocompatible matrices (gene-activated matrix, or GAM). The matrix also serves as a scaffold for cellular in-growth and subsequent gene uptake and expression. An adenoviral vector encoding human platelet-derived growth factor-B delivered in collagen (AdPDGF-B/GAM) has demonstrated efficacy in models of wound repair. The safety, biodistribution, and immunogenicity profiles of AdPDGF-B/GAM were examined using a rabbit dermal wound model. Four weekly doses at 1 x 10(10) and 1 x 10(11) viral particles/cm2 of wound surface stimulated dose-related increases in granulation tissue formation and cell proliferation. In situ hybridization and immunostaining demonstrated concordant expression of human PDGF-B mRNA and protein. No treatment-related changes in hematology, serum chemistry, or histopathology were observed. Although AdPDGF-B DNA and PDGF-B mRNA were detected in wounds and axillary lymph nodes of treated animals, no AdPDGF-B was detected in blood or other organs. No immunologic responses against collagen were observed; however, as expected, IgG responses to AdPDGF-B and human PDGF-BB protein were detected. In adenovirus-preimmunized rats, attenuation of the wound healing response was modest (approximately 16%). Collectively, these observations indicate that repeat doses of AdPDGF-B/GAM are well tolerated and lead to robust, localized tissue repair.
Comparison of Television and Telephone for Remote Medical Consultation
Authors: Gordon T. Moore, Thomas R. Willemain, Rosemary Bonanno, William D. Clark, Albert R. Martin, R. Peter Mogielnicki
Journal: New England Journal of Medicine (1975)

Television and telephone communications were randomly used to compare their effectiveness in allowing consultation between a hospital-based physician and remote nurse practitioners. Visits using television for consultation averaged 50 minutes as compared with 40 minutes for telephone. This difference was caused by longer work-ups before the consultation, longer delays after it was requested, and longer consultations, themselves, on television. However, television consultations resulted in significantly fewer immediate referrals of patients to hospital physicians: 6 plus or minus 1 as compared to 12 plus or minus 1 per cent (mean plus or minus S.E.M) OF ALL TELEPHONE CONSULTATIONS (P SMALLER THAN 0.005). Although no overall difference in satisfaction was documented between the results of television and telephone consultations, participants preferred the former for medical decision making and cited it for allowing more social interaction than telephone. These findings suggest that television may have its greatest value in remote sites where the sense of isolation is great and the need to reduce long-distance referrals offsets the costs of the system.
Severe Malnutrition Assessment in Children in Rural Kenya
Authors: C. G. Hogness
Journal: JAMA (2005)

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
Depression of cellular immunity as an index of malnutrition in surgical patients.
Authors: A McIrvine, J Wolfe
Journal: BMJ (1981)

globulin have a strong but not exclusive influence.' Changes in albumin have only a minor effect, but paraproteins2 and lipoproteins3 also increase plasma and serum viscosity.For these reasons estimations of plasma fibrinogen from the difference of plasma and serum viscosity are unreliable and can be wrong by as much as 100",.
955. Utilising Viral Gene Transfer to Model Polyglutamine Diseases and Study the Effects of Heat Shock Proteins
Authors: Joanna L. Howarth, Stephen Kelly, Colin P.J. Glover, Michael E. Cheetham, Alison S. Bienemann, Darren J. Heywood, Russell J. Hobson, Jean-Marc Gallo, James B. Uney
Journal: Molecular Therapy (2005)

Polyglutamine Disorders, such as Spinal Bulbar Muscular Atrophy (SBMA) and Huntington's disease, are characterised by selective neuronal loss. Typically beginning in mid-life and involving a specific subset of neurones, these disorders are the result of an expanded CAG repeat codon tract within the affected gene. This expansion leads to the translation of a mutant protein, resulting in the production of protein aggregates, the characteristic hallmark of these disorders. The exact mechanisms of these diseases and the function of these aggregates are yet to be fully elucidated. Altered molecular chaperone function, the Ubiquitin Proteosome System (UPS) and altered signalling via transcription factors are thought to be involved (Steffan et al, 2001). Additional research has demonstrated that some chaperone molecules, including hsp40, can increase the solubility of expanded repeats, leading to enhanced degradation and a decrease in protein aggregation within various cells types (Bailey C et al, 2002).
Cardiotrophin-1 eliminates hepatic steatosis in obese mice by mechanisms involving AMPK activation
Authors: David Castaño, Eduardo Larequi, Idoia Belza, Alma M. Astudillo, Eduardo Martínez-Ansó, Jesús Balsinde, Josepmaria Argemi, Tomás Aragon, María J. Moreno-Aliaga, Jordi Muntane, Jesús Prieto, Matilde Bustos
Journal: Journal of Hepatology (2013)
Is This the Time to Introduce Minimal Residual Disease in Multiple Myeloma Clinical Practice?
Authors: Bruno Paiva, Noemi Puig, Ramón García-Sanz, Jesús F. San Miguel
Journal: Clinical Cancer Research (2015)

Increasing therapeutic options and prolonged survival in multiple myeloma have raised interest in the concept of depth of response and its importance to predict patients' outcomes. Although the efficacy of current treatment approaches has greatly improved in the past decade, the definition of complete response (CR) remains unaltered and continues to use conventional serological and morphologic techniques. That notwithstanding, there is growing interest in minimal residual disease (MRD) monitoring, which has emerged in recent years as one of the most relevant prognostic factors in multiple myeloma. MRD can be assessed both inside (e.g., immunophenotypic and molecular techniques) and outside the bone marrow (e.g., PET/CT). Here, we focus on flow- and molecular-based assays by which different cooperative groups have demonstrated the efficacy of MRD assessment to predict outcomes even among patients in CR, and irrespectively of disease risk. Although further standardization is still required, the time has come to implement MRD monitoring in prospective clinical trials as a sensitive tool to evaluate treatment efficacy and for risk-adapted treatment, particularly in the consolidation and maintenance settings. Here, we present a comprehensive and critical review on the methodologic aspects, specific characteristics, and clinical significance of MRD monitoring by flow cytometry, PCR, and next-generation sequencing.