tbuckley/cabot-search huggingface dataset:
Luteolin Promotes Degradation in Signal Transducer and Activator of Transcription 3 in Human Hepatoma Cells: An Implication for the Antitumor Potential of Flavonoids
Authors: Karuppaiyah Selvendiran, Hironori Koga, Takato Ueno, Takafumi Yoshida, Michiko Maeyama, Takuji Torimura, Hirohisa Yano, Masamichi Kojiro, Michio Sata
Journal: Cancer Research (2006)

Abstract In this study, we have investigated the underlying molecular mechanism for the potent proapoptotic effect of luteolin on human hepatoma cells both in vitro and in vivo, focusing on the signal transducer and activator of transcription 3 (STAT3)/Fas signaling. A clear apoptosis was found in the luteolin-treated HLF hepatoma cells in a time- and dosage-dependent manner. In concert with the caspase-8 activation by luteolin, an enhanced expression in functional Fas/CD95 was identified. Consistent with the increased Fas/CD95 expression, a drastic decrease in the Tyr705 phosphorylation of STAT3, a known negative regulator of Fas/CD95 transcription, was found within 20 minutes in the luteolin-treated cells, leading to down-regulation in the target gene products of STAT3, such as cyclin D1, survivin, Bcl-xL, and vascular endothelial growth factor. Of interest, the rapid down-regulation in STAT3 was consistent with an accelerated ubiquitin-dependent degradation in the Tyr705-phosphorylated STAT3, but not the Ser727-phosphorylated one, another regulator of STAT3 activity. The expression level of Ser727-phosphorylated STAT3 was gradually decreased by the luteolin treatment, followed by a fast and clear down-regulation in the active forms of CDK5, which can phosphorylate STAT3 at Ser727. An overexpression in STAT3 led to resistance to luteolin, suggesting that STAT3 was a critical target of luteolin. In nude mice with xenografted tumors using HAK-1B hepatoma cells, luteolin significantly inhibited the growth of the tumors in a dosage-dependent manner. These data suggested that luteolin targeted STAT3 through dual pathways—the ubiquitin-dependent degradation in Tyr705-phosphorylated STAT3 and the gradual down-regulation in Ser727-phosphorylated STAT3 through inactivation of CDK5, thereby triggering apoptosis via up-regulation in Fas/CD95. (Cancer Res 2006; 66(9): 4826-34)
RELATIONSHIP BETWEEN CARDIOLOGY PRACTICE TEACHING STATUS AND IMPROVEMENT IN THE USE OF EVIDENCE-BASED THERAPY FOR HEART FAILURE: FINDINGS FROM IMPROVE HF
Authors: Christopher M. O’Connor, Gregg C. Fonarow, Nancy M. Albert, Anne B. Curtis, Wendy Gattis Stough, Mihai Gheorghiade, J Thomas Heywood, Mark L. McBride, Patches Johnson Inge, Mandeep R. Mehra, Dwight Reynolds, Mary N. Walsh, Clyde W. Yancy
Journal: Journal of the American College of Cardiology (2010)
Biosynthesis and Secretion of Follicle-Stimulating Hormone*
Authors: SCOTT C. CHAPPEL, ALFREDO ULLOA-AGUIRRE, CHRISTOS COUTIFARIS
Journal: Endocrine Reviews (1983)

THE ANTERIOR pituitary gland synthesizes and secretes three glycoprotein hormones. Two of these, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are termed gonadotropins and exert divergent effects upon the gonads to regulate and maintain essential reproductive processes such as gametogenesis, steroidogenesis, and ovulation. We possess a basic understanding of the role played by both gonadotropins in a wide variety of physiological processes associated with reproduction. This review is intended to provide a concise body of information regarding the biological processes associated with the biosynthesis and secretion of FSH. Since both gonadotropins appear to be synthesized by the same cell in the anterior pituitary gland (1, 2) and the biosynthetic and secretory processes are influenced by the same hypothalamic hormone, gonadotropin-releasing hormone (GnRH) (3), this review will consider a great deal of information obtained from the study of both gonadotropins. However the primary focus will be the biochemical, physiological, and neuroendocrine studies relative to FSH.
REMOVAL OF FILARIA LOA FROM CONJUNCTIVA
Authors: G. H. Beers
Journal: JAMA (1924)

A woman, aged 45, a Presbyterian missionary on a furlough from a station in Cameroons, West Africa, stated that at times during the past year she had felt the sensation of a foreign body and a slight pinching in the left eye. She had seen an "eye worm" on several occasions, but it had disappeared before she was able to get a surgeon. May 27, 1924, the patient called me on the telephone, saying that the "worm" was in sight. Hurrying to her, I could easily see the filaria lying under the conjunctiva of the left eye, horizontally about 3 mm. above the limbus. A loop of the worm was immediately grasped with fixation forceps, and the cocain solution instilled afterward. Then a snip through the conjunctiva, and the filaria was extracted intact. It measured 38 mm. and looked like an animated piece of silkworm catgut. The patient states that
Autoimmune Haemolytic Anaemia and Mefenamic Acid Therapy
Authors: G. L. Scott, A. B. Myles, P. A. Bacon
Journal: BMJ (1968)

Three patients developed autoimmune haemolytic anaemia while being treated with mefenamic acid. In each case the autoimmune haemolytic anaemia was of the warm antibody gammaG type, and the antibodies had some rhesus specificity. All three patients recovered when the drug was withdrawn.Attempts to inhibit or enhance the activity of the antibody in vitro were unsuccessful.Direct antihuman globulin tests were made in.the red cells of 36 patients receiving long-term mefenamic acid therapy, but only one was found to be transitorily positive.
Modernising mental health services
Authors: M. Marshall
Journal: BMJ (1999)

In Modernising Mental Health Services , the new national mental health strategy for England announced in December, 1 2 the government lays out detailed plans for reforming general psychiatric services, and places them in the context of its wider NHS reforms. The document asserts that “community care has failed” and blames underfunding, inadequate services, overburdening of families, problems in recruiting and retaining staff, and an outdated legal framework. It then describes a strategy for providing a service “in which patients, carers and the public are safe and where security and support is provided to all.” This strategy has two key elements: increased investment and increased control (over patients and clinicians).

The increased investment consists of =A3700m spread over three years. These extra funds will provide more beds (in hostels and secure units); outreach teams and 24 hour access; new treatments, including atypical neuroleptics; and staff training. Increased control of patients will be achieved by “modernising” mental …
Suppression of body fat accumulation in myostatin-deficient mice
Authors: Alexandra C. McPherron, Se-Jin Lee
Journal: Journal of Clinical Investigation (2002)

Myostatin is a TGF-β family member that acts as a negative regulator of muscle growth. Mice lacking the myostatin gene (Mstn) have a widespread increase in skeletal muscle mass resulting from a combination of muscle fiber hypertrophy and hyperplasia. Here we show that Mstn-null mice have a significant reduction in fat accumulation with increasing age compared with wild-type littermates, even in the setting of normal food intake (relative to body weight), normal body temperature, and a slightly decreased resting metabolic rate. To investigate whether myostatin might be an effective target for suppressing the development of obesity in settings of abnormal fat accumulation, we analyzed the effect of the Mstn mutation in two genetic models of obesity, agouti lethal yellow (Ay) and obese (Lepob/ob). In each case, loss of Mstn led to a partial suppression of fat accumulation and of abnormal glucose metabolism. Our findings raise the possibility that pharmacological agents that block myostatin function may be useful not only for enhancing muscle growth, but also for slowing or preventing the development of obesity and type 2 diabetes.
Abstract 4140: Negative enrichment of circulating tumor cells using geometrically activated surface interaction (GASI) chip.
Authors: Hyo-Il Jung, Kyung-A Hyun, Tae Yoon Lee
Journal: Cancer Research (2013)

Abstract Circulating tumor cells (CTCs), existing extremely rare in peripheral blood (the order of one cell per 1* 106 nucleated cells), have attracted a lot of attention as they can be exploited to investigate metastasis. The isolation of intact CTCs is challenging owing to their rarity and heterogeneous features. A lot of methodologies for CTCs enrichment in blood were focused using antibodies to epithelial cell adhesion molecule (EpCAM). However, the recent studies found that the CTCs undergo a process of epithelial-mesenchymal transition (EMT) to adapt oneself to new circumstances which is blood stream and down regulated EpCAM expression on their surface. It is thought that the many CTCs may escape detection by conventional detection methods. So, we decided to use the negative enrichment (i.e. capturing WBCs which are non-target cells and eluting CTCs which are target cells) for isolation of intact and heterogeneous CTCs. To capture a large number of WBCs in the channel, we developed a geometrically activated surface interaction (GASI)-Chip which is based on the asymmetric herringbone that generate the enhanced mixing flows increasing the surface interaction between the WBCs and CD45 antibody-conjugated channel surface. Using the optimized experimental conditions, we isolated 94.67% of MCF-7 cells (breast cancer cell line) and eliminated 98.94% of Jurkat cells (human T cell lymphoblast like cell line) at 20 μL/min flow rate. Based on these results, we have attempted to isolate CTCs from patients with several kinds of metastatic cancer patients under the same conditions. The blood samples (1ml) were collected from breast, gastric and lung cancer patients, respectively. After blood samples passed through the GASI-Chip, collected cells were fixed on a slide glass and stained with DAPI for DNA content, PE conjugated Cytokeratin for CTC, and FITC conjugated CD45 for WBC. Following imaging the slide glass, captured images were examined carefully with predefined criteria (DAPI positive, Cytokeratin positive, CD45 negative). The number of isolated CTCs varied from 1 to 51 in 1 ml of blood. Although this device was not intended to process full clinical blood draws, which typically yield 7.5 mL, quite a number of CTCs can be detected from only 1ml of blood compared with other approaches based on the characters of CTCs such as size. Furthermore, the intact and heterogeneous CTCs can be isolated regardless of EpCAM expression because our devices do not require any labeling processes (e.g., EpCAM antibody for CTC). Citation Format: Hyo-Il Jung, Kyung-A Hyun, Tae Yoon Lee. Negative enrichment of circulating tumor cells using geometrically activated surface interaction (GASI) chip. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4140. doi:10.1158/1538-7445.AM2013-4140
Primary HIV-1 infection: a new medical emergency?
Authors: S. Jolles, S. K. De Loes, M. A Johnson, G. Janossy
Journal: BMJ (1996)

Patients with HIV-1 infection are usually not diagnosed until they present with an opportunistic infection, often several years after their initial seroconversion. Increasingly, however, it is recognised that many people suffer an acute mononucleosis-like illness shortly after seroconversion. Despite the protean manifestations of this initial infection, primary HIV-1 infection is now recognisable as a distinct clinical entity. The clinical findings are associated with the immune response to the rapid dissemination of HIV throughout the body and may represent an important early opportunity for diagnosis and intervention.

Primary HIV-1 infection has been described as a “mononucleosis-like illness of acute onset occurring 2-6 weeks after HIV-1 infection, usually resolving after 1-2 weeks, though occasionally lasting considerably longer.”1 2 It has been estimated that 53-93% of gay men who have recently acquired HIV undergo an acute seroconversion illness and that most of them remain undiagnosed.3 Those with a severe and long lasting illness have a poorer long term prognosis.4

The symptoms associated with primary HIV-1 …
Statement of the Committee on Morals and Ethics of the Transplantation Society
Authors: JOHN P. MERRILL
Journal: Annals of Internal Medicine (1971)

Special Articles1 October 1971Statement of the Committee on Morals and Ethics of the Transplantation SocietyJOHN P. MERRILL, M.D.JOHN P. MERRILL, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-4-631 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe years 1960 to 1970 saw the development of a swell of opinion of which ripples had been evident in the preceding decade. Increasingly, all segments of society have become aware of and audibly responsive to the moral and social impact of their interests and creative work. From within and without the scientific community this awareness has taken many forms; self-security and concern with the effects of advances in knowledge and technology upon ecology, population control, national posture, and a multitude of other social problems. The protein chemist has given us his opinion on nuclear testing and the pediatrician his... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts▸From the Committee on Morals and Ethics of the Transplantation Society. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEpistemic Communities, Human Rights, and the Global Diffusion of Legislation against the Organ TradeDonating a Kidney in Taiwan: A Study of 90 Relative Living DonorsThe Transplantation Society: A Global PresenceLiving Kidney Donation: Evolution and Technical Aspects of Donor NephrectomyLiving donor transplant: wider selection criteriaReimbursement, 'rewarded gifting', financial incentives and commercialism in living organ donationPreventing Commercial Transactions in Human Organs and Tissues: An International Overview of Regulatory and Administrative MeasuresEthical Issues in Brain Death and Multiorgan TransplantationRenal transplantationUse of living donors in renal transplantationRenal Transplantation in ChildrenEthische und rechtliche Probleme der OrgantransplantationBrain DeathAltruism and Coercion: Should Children Serve as Kidney Donors?Cadaveric Kidneys for Transplantation: Is There a Need for More?Medizinische Extremsituationen und der sterbende PatientOrgan Donation: For Whose Sake?CARL H. FELLNER, M.D.Ethical and Moral Problems in the Use of Artificial and Transplanted OrgansAttitudes, Practices, and Ethical Positions among Transplant Centers Concerning Living Kidney Donor SelectionEthical issues in living related donors 1 October 1971Volume 75, Issue 4Page: 631-633KeywordsChemistsEcologyPostural controlProteinsTransplantation Issue Published: 1 October 1971 PDF DownloadLoading ...
Hypoxia of the Renal Medulla — Its Implications for Disease
Authors: Mayer Brezis, Seymour Rosen
Journal: New England Journal of Medicine (1995)

In land mammals, a major task of the kidney is to reabsorb water to allow survival in a dry environment. Water conservation is enhanced by the renal medulla, which concentrates the urine to a level up to four times the osmolality of plasma. To produce this unique gradient of osmolality, the medulla has a countercurrent system of vessels and tubules that dictates active reabsorption of sodium in a milieu poor in oxygen (Figure 1).1 In this review, we describe how hypoxia of the medulla may relate to susceptibility to acute and chronic renal injury.The Renal Medullary Concentrating Mechanism as . . .
PHYSIOLOGIC COLECTOMY IN CHRONIC TOXEMIAS OF INTESTINAL ORIGIN
Authors: CHARLES A. L. REED
Journal: JAMA (1918)

The cumulative experience of both physicians and surgeons engaged in a large way with the treatment of gastro-intestinal conditions, and of experimental scientists in dealing with these problems, tends to confirm what may be expressed as at least tentative conclusions as follows:   The origin of certain toxins and of the now recognized anaphylatoxin 1 demonstrated to be present in certain toxemias, both convulsive and nonconvulsive in type, is due to certain conditions of stasis in the gastro-intestinal tract.  Stasis in the gastro-intestinal tract implies (a) fecal retardation in either the small intestine or the colon or both; (b) venous retardation in either the mesocolic circulation or the mesenteric circulation or both, and (c) retardation in the lymphatic circulation of both the mesocolon and the mesentery.  These three forms of stasis are associated with and obviously dependent on some form of gastro-intestinal displacement or other distortion, and are, therefore, primarily mechanical in
Increasingly complex births and tired staff threaten safety of maternity patients, King's Fund finds
Authors: M. Pownall
Journal: BMJ (2009)

Exhausted staff, lack of leadership, and an increasingly complex case mix are jeopardising the safety of maternity patients, claims a new report from the health think tank the King’s Fund.

Its report is the result of a series of regional meetings held across England of obstetricians, midwives, and risk managers, who have echoed concerns raised in a previous King’s Fund report, Safe Birth: Everybody’s Business, and a 2007 survey by the healthcare services watchdog, the Healthcare Commission, now the Care Quality Commission.

Widespread difficulty in recruiting and retaining midwives with more than a couple of years of …
Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q.
Authors: B Ghebrehiwet, B L Lim, E I Peerschke, A C Willis, K B Reid
Journal: The Journal of Experimental Medicine (1994)

This work describes the functional characterization, cDNA cloning, and expression of a novel cell surface protein. This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular "heads" of C1q molecules, at physiological ionic strength, and also to inhibit complement-mediated lysis of sheep erythrocytes by human serum. The NH2-terminal amino acid sequence of the first 24 residues of the C1q-binding protein was determined and this information allowed the synthesis of two degenerate polymerase chain reaction primers for use in the preparation of a probe in the screening of a B cell cDNA library. The cDNA isolated, using this probe, was found to encode a pre-pro protein of 282 residues. The NH2 terminus of the protein isolated from Raji cells started at residue 74 of the predicted pre-pro sequence. The cDNA sequence shows that the purified protein has three potential N-glycosylation residues and is a highly charged, acidic molecule. Hence, its binding to C1q may be primarily but not exclusively due to ionic interactions. The "mature" protein, corresponding to amino acid residues 74-282 of the predicted pre-pro sequence, was overexpressed in Escherichia coli and was purified to homogeneity. This recombinant protein was also able to inhibit the complement-mediated lysis of sheep erythrocytes by human serum and was shown to be a tetramer by gel filtration in nondissociating conditions. Northern blot and RT-PCR studies showed that the C1q-binding protein is expressed at high levels in Raji and Daudi cell lines, at moderate levels in U937, Molt-4, and HepG2 cell lines, and at a very low level in the HL60 cell line. However, it is not expressed in the K562 cell line. Comparison of gC1q-R NH2-terminal sequence with that of the receptor for the collagen-like domain of C1q (cC1q-R) showed no similarity. Furthermore, antibodies to gC1q-R or an 18-amino acid residue-long NH2-terminal synthetic gC1q-R peptide did not cross-react with antibodies to cC1q-R. Anti-gC1q-R immunoblotted a 33-kD Raji cell membrane protein, whereas anti cC1q-R recognized a molecule of approximately 60 kD. The NH2-terminal sequence of gC1g-R appears to be displayed extracellularly since anti-gC1g-R peptide reacted with surface molecules on lymphocytes, polymorphonuclear leukocytes, and platelets, as assessed by flow cytometric and confocal laser scanning microscopic analyses.(ABSTRACT TRUNCATED AT 400 WORDS)
Much still needs to be done in England to tackle health inequalities, health department admits
Authors: Roger Dobson
Journal: BMJ (2007)

Men and women living in the north of England can expect to live two years less than those in the south, latest government statistics show.

A north-south divide—with higher rates of smoking, more deaths from smoking, more binge drinking, and twice as many families receiving means tested benefits in areas of the north—continues to exist, says a new report from the Department of Health.

Twice as many men in the North East governmental region as in the South East think they are in poor health, and the number of hospital admissions for alcohol related conditions in the North West is 2.5 times that in the East of England region (East Anglia, Bedfordshire, Hertfordshire, and Essex).

“There is a consistent ‘north-south' divide, …
Left Ventricular Stress and Compliance in Man
Authors: WILLIAM H. GAASCH, WILLIAM E. BATTLE, ALLEN A. OBOLER, JOHN S. BANAS, HERBERT J. LEVINE
Journal: Circulation (1972)

Left ventricular circumferential end-diastolic stress (Sed), peak systolic stress (Sps), and compliance at end-diastole ([dV/VdP]ed) were estimated in 13 subjects with normal left ventricles (N group), nine subjects with inappropriate hypertrophy (IH group), five with aortic valvular stenosis (AS group), and six with congestive cardiomyopathy (CC group). The product of Sed and (dV/dP)ed was employed as an index of "muscle fiber stretch" and related to systolic indices of ventricular performance. Compliance was significantly less than normal in IH ( P &lt; 0.001), in AS ( P &lt; 0.01), and in CC ( P &lt; 0.001), while end-diastolic volumes were smaller than normal ( P &lt; 0.05), normal ( P = ns ), and larger than normal ( P &lt; 0.001) in the three groups, respectively. Sed was normal in IH and AS but elevated in CC ( P &lt; 0.001), while Sps was decreased in IH and normal in AS and CC. "Muscle fiber stretch," however, was substantially less than normal in IH ( P &lt; 0.001), indicating that the low Sps is due at least in part to short sarcomeres. In CC, despite a markedly elevated preload, "muscle fiber stretch" was normal ( P = ns ), while work indices of the ventricle were diminished indicating depressed ventricular function. Thus, the product of Sed and (dV/VdP) ed provides a normalized index of "muscle fiber stretch," which permits one to compare length-tension or length-work relationships in diseased ventricles of varying dimensions and compliance.