tbuckley/cabot-search huggingface dataset:
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE, APOPTOSIS, AND NEURODEGENERATIVE DISEASES
Authors: De-Maw Chuang, Christopher Hough, Vladimir V. Senatorov
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Increasing evidence supports the notion that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a protein with multiple functions, including its surprising role in apoptosis. GAPDH is overexpressed and accumulates in the nucleus during apoptosis induced by a variety of insults in diverse cell types. Knockdown of GAPDH using an antisense strategy demonstrates its involvement in the apoptotic cascade in which GAPDH nuclear translocation appears essential. Knowledge concerning the mechanisms underlying GAPDH nuclear translocation and subsequent cell death is growing. Additional evidence suggests that GAPDH may be an intracellular sensor of oxidative stress during early apoptosis. Abnormal expression, nuclear accumulation, changes in physical properties, and loss of glycolytic activity of GAPDH have been found in cellular and transgenic models as well as postmortem tissues of several neurodegenerative diseases. The interaction of GAPDH with disease-related proteins as well as drugs used to treat these diseases suggests that it is a potential molecular target for drug development.
The Internist's Reading: Doctors at the Heart of the Novel
Authors: Rita Charon
Journal: Annals of Internal Medicine (1994)

Literature of Medicine1 September 1994The Internist's Reading: Doctors at the Heart of the NovelRita CharonRita CharonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-5-199409010-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The bonds between medicine and literature are natural and nourishing, for doctors are storytellers, intimates of strangers, seekers of plot, diviners. We do our work by listening to stories and knowing the meaning of things. Said semiotician and critic Roland Barthes: “Now, this is precisely what diagnosis is: an act of reading a configuration of signs” [1].When a novelist of the rank of Henry James or George Eliot chooses to place a doctor at the center of a novel, we gather around to hear, to see, to witness our work in the hands of a creative genius. It is ...References1. Barthes R. Semiology and medicine. In: Howard R, trans. The Semiotic Challenge. New York: Hill and Wang; 1988:209. Google Scholar2. Freud S. Civilization and its discontents. In: Strachey J, ed. and trans. The Standard Edition of the Complete Psychological Works of Sigmund Freud. Vol. 21. London: Hogarth Press; 1953-74:133. Google Scholar3. Benjamin W. The Storyteller. In: Arendt H, ed. and Zohn H, trans. Illuminations. New York: Shocken Books; 1969:101. Google Scholar4. James H. The middle years. In: The Novels and Tales of Henry James: The New York Edition. Vol. 16. New York: Charles Scribner's Sons; 1909:105. Google Scholar5. Rothfield L. Disarticulating Madame Bovary: Flaubert and the medicalization of the real. In: Vital Signs: Medical Realism in Nineteenth-Century Fiction. Princeton: Princeton University Press; 1992:15-45. Google Scholar6. Shuttleworth S. George Eliot and Nineteenth-Century Science: The Make-Believe of a Beginning. Cambridge: Cambridge University Press; 1984. Google Scholar7. Charon R. The great empty cup of attention: the doctor and the illness in The Wings of the Dove. Literature and Medicine. 1990; 9:105-24. Google Scholar8. Weigand HJ. “The Magic Mountain”: A Study of Thomas Mann's Novel “Der Zauberberg.” Chapel Hill: The University of North Carolina Press; 1964. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHumanistic Qualities in End-of-Life Care: Lessons from The Diving Bell and the Butterfly: A Memoir of Life in Death —Required Reading in an End-of-Life Care Curriculum for Internal Medicine Residents 1 September 1994Volume 121, Issue 5Page: 390-391KeywordsBirthBoneBone fractureEmotionsEngineersFallsHeartMotivationTraditional medicine ePublished: 15 August 2000 Issue Published: 1 September 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The rise of the doctor-manager
Authors: Michael Day
Journal: BMJ (2007)

It's not just patients who might benefit from more doctors but the service itself, according to the UK National Health Service's chief executive, David Nicholson. He told the annual conference of staff grade and associate specialist doctors in June, “Within two years, we want a doctor applying for every chief executive post advertised. Where clinicians and managers work together,” he said, “There is almost nothing you can't achieve.”

Leading doctors have welcomed the call for more clinical input in the running of the NHS, although many have raised doubts about whether Mr Nicholson's two year deadline for getting medical applications for all chief executive posts is remotely realistic.

None the less, after the Conservative party's pledge to do away with central NHS targets, the pressure on the government has increased to give local clinical concerns higher priority.

Mr Nicholson is relying on the appointment within the next two or three weeks of the first NHS medical director, to speed up the process. He is understood to be reluctant to comment further until the medical director has had a chance to establish his or her position on what has become a key policy area for the NHS.
Enhanced release of inflammatory mediators from lithium-stimulated neutrophils in psoriasis
Authors: F.J. BLOOMFIELD, MARJORIE M.YOUNG
Journal: British Journal of Dermatology (1983)

We have used lithium salts to stimulate degranulation in order to assess neutrophil activity in psoriasis. Evidence is presented for significant enhancement of degranulation of β- glucuronidase (primary granules) and vitamin Bi2-binding protein (secondary granules) from lithium-stimulated neutrophils in psoriatic whole blood. Basal levels of granule markers showed no significant difference between normal and psoriatic neutrophils. On the other hand, enzymes associated with neutrophil function (myeloperoxidase and catalase) were found to be markedly increased in resting psoriatic neutrophils. An important recent development has been the observation that psoriatic neutrophils are 'activated' in terms of their neutrophil function. Wahba et al. (1978, 1979) observed enhanced chemotactic and phagocytic properties of isolated psoriatic neutrophils, and Sedgwick, Bergstresser & Hurd (1979, 1980) demonstrated increased adherence of isolated psoriatic neutrophils to glass-wool and nylon fibres. Recently, there have been a number of reports concerning the clearing of psoriasis in patients undergoing haemodialysis and peritoneal dialysis (McEvoy & Kelly, 1976; Buselmeier et al., 1979; Glinski et al., 1979), and it is now believed that improvement was a result of removal of neutrophils rather than some psoriatogenic factor. Lithium salts are commonly used in the treatment of bipolar affective psychosis. Lazarus & Gilgor (1979) drew attention to reports that lithium salts adversely affect the course of psoriasis by direct or indirect mechanisms. They may do so by affecting neutrophil function, thus establishing a relationship between psoriasis and neutrophil activity. Lithium salts can dramatically affect neutrophil activity in terms of granulopoiesis, turnover and migration (Rothstein et al., 1978). We have recently demonstrated that lithium salts have the capacity to induce directly the release of inflammatory mediators from neutrophils in normal whole blood, in the absence of phagocytic stimulation (Bloomfield & Young, 1982). The objective of this investigation was to demonstrate that lithium salts are capable of causing enhanced degranulation from psoriatic neutrophils. In addition, the results would demonstrate in vitro the possible effects which lithium might have in exacerbating psoriasis in vivo, i.e. by causing release of inflammatory mediators from neutrophils which have been shown to be activated.
HETEROTRANSPLANTATION OF FROG CARCINOMA; CHARACTER OF GROWTH IN THE EYES OF ALIEN SPECIES
Authors: Balduin Lucké, H. Schlumberger
Journal: The Journal of Experimental Medicine (1940)

Transplantation into foreign hosts of the kidney carcinoma of leopard frogs has been investigated by grafting the tumor in the anterior chamber of two other species belonging to the same family of frogs (green frog, bullfrog), of a species from a different family (the toad), and of animals of different classes of cold-blooded vertebrates (goldfish, alligator). In the eyes of frogs of alien species, the kidney carcinoma became established as readily as in the eye of the natural host. In toads, the proportion of successful transplantation was slightly less. No progressive growth of transplanted tumor occurred in the fish or the reptile, although in fish characteristic tumor acini persisted and a few mitoses were to be found long after implantation. In the alligator the transplants deteriorated much more rapidly. Thus the success of transplantation into alien species decreased as the relationship to the original species became more distant. An inflammatory reaction to the tumor graft appeared in the eye of reptiles and fish, but no such reaction occurred in amphibians. The character and rate of growth of transplants were followed by continued direct examination with the microscope and were found to be practically the same in the eye of alien species as in the original species. Nor were differences in the finer structure of the tumor observed in the several species. The neoplastic cells retained their acinar arrangement, supported by stroma which developed quite as well from the tissues of alien hosts as from those of the natural host. It was possible to engraft the tumor in the eye of the natural host, then to transplant it into the eye of another species, and finally to retransplant it in the original species. In this way the tumor has been propagated for 443 days. A tissue culture of the tumor has been successfully transplanted into the eye of an alien host. Thus these results demonstrate that, among cold-blooded vertebrates, the humors and tissues of the eye have a high degree of tolerance for foreign tumor grafts.
A flow cytometry‐based assay for measuring invasion of red blood cells by <i>Plasmodium falciparum</i>
Authors: Amy K. Bei, Tiffany M. DeSimone, Aida S. Badiane, Ambroise D. Ahouidi, Tandakha Dieye, Daouda Ndiaye, Ousmane Sarr, Omar Ndir, Souleymane Mboup, Manoj T. Duraisingh
Journal: American Journal of Hematology (2010)

Variability in the ability of the malaria parasite Plasmodium falciparum to invade human erythrocytes is postulated to be an important determinant of disease severity. Both the parasite multiplication rate and erythrocyte selectivity are important parameters that underlie such variable invasion. We have established a flow cytometry-based method for simultaneously calculating both the parasitemia and the number of multiply-infected erythrocytes. Staining with the DNA-specific dye SYBR Green I allows quantitation of parasite invasion at the ring stage of parasite development. We discuss in vitro and in vivo applications and limitations of this method in relation to the study of parasite invasion.
Prevalence of retinopathy in a diabetic clinic.
Authors: R J Donovan
Journal: BMJ (1978)

In a prospective study lasting 14 months an attempt was made to measure the visual acuity and examine the fundi, after mydriasis, of all patients attending the diabetic clinic of a district general hospital. Of 704 patients, 160 (22.7%) had some evidence of retinopathy, and 52 (7.4%) of these were already attending an ophthalmologist. A further 18 (2.6%) were known to have retinopathy and were being followed up in the diabetic clinic. Ninety (12.8%) new patients with diabetic retinopathy were discovered. Most had minimal changes, but 30 (4.3%) were considered to have changes severe enough to be referred to an ophthalmologist. Twenty-two (2.1%) underwent, or were awaiting, photocoagulation, and half of these had had no visual symptoms when first seen. Although some of these patients were already being treated or observed for retinopathy, it is encouraging that relatively few new patients needing treatment for retinopathy were discovered. If retinopathy could be detected early enough physicians might be able to deal with it and so ease pressure on ophthalmological services.
Obama vows to defend key elements of Affordable Care Act
Authors: M. McCarthy
Journal: BMJ (2014)

President Barack Obama said on 5 November that he was open to hearing ideas from Republicans on reforming the Affordable Care Act but that he would use his executive powers to defend its key elements.

Obama made his comments in a press conference called the day after an election day rout in which Republicans took control of the US Senate and expanded their majority in the House of Representatives.1

“There are certainly some lines I’m going to draw,” the president said. “Repeal of the law, I won’t sign. Efforts that would take away healthcare from the 10 million …
Results of Operation for Atrial Septal Defect in Patients Forty-five Years of Age and Older
Authors: GEORGE R. DAICOFF, ROBERT O. BRANDENBURG, JOHN W. KIRKLIN
Journal: Circulation (1967)

1. The results of closure of atrial septal defects in 155 patients over 45 years of age have been reviewed. 2. The over-all operative mortality rate was 6.5%; the operative mortality rate in the last 48 patients was 2.1%. 3. The late results of operation were considered excellent in 83% and good in 13% of the patients. 4. Long-term follow-up studies suggest that patients have significantly longer survival with closure of their defects. 5. It is concluded that operation for atrial septal defect in the older patient may be done at a low risk with an excellent prospect of a good, long-term result in almost all cases.
Long-Term Danazol Therapy in Autoimmune Thrombocytopenia: Unmaintained Remission and Age-Dependent Response in Women
Authors: Yeon S. Ahn
Journal: Annals of Internal Medicine (1989)

Study Objective: To assess the long-term benefit and side effects of danazol therapy, and to delineate factors influencing the responses in patients with autoimmune thrombocytopenia. Design: Before and after trial. Setting: Referral-based hematology clinics and the University of Miami teaching hospitals. Patients: Data were collected on 96 patients (60 women and 36 men, 45 of whom had had splenectomies) receiving danazol therapy for autoimmune thrombocytopenia and analyzed. Intervention: Danazol was added to the previous therapy or begun as an initial therapy. Glucocorticoids were tapered gradually. Measurements and Main Results: The overall response rate to danazol was 61.4%. Among responders, the platelet counts (mean ± SD) before and after danazol treatment were 36 ± 24 x 109/L and 145 ± 77 x 109/L, respectively, and the time to response was 2.7 ± 3 months. Sex, age, and the status of the spleen (absent or present) influenced the responses to danazol: In women, but not in men, response rates improved with advancing age, especially in the nonsplenectomized women. This may be because estrogen levels are high in younger women and low in older women and men. Danazol, when given longer than a year, induced remissions lasting for years even after its discontinuation, but early relapses were frequent when danazol was administered for less than 6 months. Platelet-associated IgG returned to normal range during unmaintained remission. Conclusion: Danazol is best suited for long-term medical management of autoimmune thrombocytopenia. It is well tolerated, and lasting, unmaintained remissions often occur after prolonged danazol administration. Age, sex, and the status of the spleen influence the responses. When danazol therapy is used, glucocorticoids can be substantially reduced in dosage or withdrawn. Danazol is a good alternative to splenectomy in elderly persons, especially in women.
Abstract ES01-1: Targeting the DNA damage response in triple negative breast cancer
Authors: D Cortez
Journal: Cancer Research (2013)

Abstract Triple negative breast cancer (TNBC) comprises approximately 25 percent of breast cancer deaths. There is a critical need to develop better therapeutic options for TNBC patients. We hypothesize that at least a subset of these cancers are especially dependent on DNA repair mechanisms that are coordinated by the ATR kinase-dependent DNA damage response signaling pathway. This hypothesis has been tested using genetic and chemical genetic approaches. We are working to develop small molecule inhibitors of the ATR pathway, understand how they work, and identify when these targeted therapies may provide clinical benefit. Our studies of an ATR selective inhibitor indicate that it kills cells due to a requirement for ATR signaling to complete DNA replication. ATR inhibition is synergistic with other chemotherapeutic agents such as platinum crosslinking drugs. ATR-inhibitor treated cells accumulate toxic DNA double-strand breaks and large stretches of single-stranded DNA through an active process catalyzed by deregulated nucleases and helicases. Effective biomarkers of ATR inhibition include DNA-PK, H2AX, RPA, and ATR phosphorylation. We have also worked with colleagues at Vanderbilt Medical School to identify additional therapeutic targets and develop small molecule inhibitors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES01-1.
Marked Esophageal Deviation Detected on Lung Imaging
Authors: RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1993)

During a ventilation (particulates)-perfusion lung scan, midline activity with a marked deviation was noted. Initially, this was thought to represent the trachea; however, chest radiographs did not demonstrate tracheobronchial deviation. The finding was due to esophageal activity, with the aortic knob possibly accounting for the deviation.
Very low dose acyclovir can be effective as prophylasix for post-herpetic erythema multiforme
Authors: R.E.A. Williams, Rosemary Lever
Journal: British Journal of Dermatology (1991)

Journal Article Very low dose acyclovir can be effective as prophylasix for post‐herpetic erythema multiforme Get access R.E.A. Williams, R.E.A. Williams Department of Dermatology, University of Glasgow and Western Infirmary, Glasgow G11 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar Rosemary Lever Rosemary Lever Department of Dermatology, University of Glasgow and Western Infirmary, Glasgow G11 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 1, 1 January 1991, Page 111, https://doi.org/10.1111/j.1365-2133.1991.tb03295.x Published: 01 January 1991
Cancer stem cell therapy using doxorubicin conjugated to gold nanoparticles via hydrazone bonds
Authors: Tian-Meng Sun, Yu-Cai Wang, Feng Wang, Jin-Zhi Du, Cheng-Qiong Mao, Chun-Yang Sun, Rui-Zhi Tang, Yang Liu, Jing Zhu, Yan-Hua Zhu, Xian-Zhu Yang, Jun Wang
Journal: Biomaterials (2013)
High and Sustained Transgene Expression in Vivo from Plasmid Vectors Containing a Hybrid Ubiquitin Promoter
Authors: Nelson S. Yew, Malgorzata Przybylska, Robin J. Ziegler, Dapei Liu, Seng H. Cheng
Journal: Molecular Therapy (2001)

Sustained transgene expression will be required for the successful treatment of most genetic diseases being considered for gene therapy. The initially high levels of expression attained with plasmid DNA (pDNA) vectors containing viral promoters, such as that from cytomegalovirus (CMV), decline precipitously to near-background levels within two to three weeks. Here we constructed pDNA vectors containing the human cellular UBB (encoding ubiquitin B; Ub) promoter and evaluated their expression in the mouse lung. Cationic lipid-pDNA complexes were instilled intranasally (IN) or injected intravenously (IV) into immunodeficient BALB/c mice. Chloramphenicol acetyltransferase (CAT) reporter gene expression from the UBB promoter was initially very low at day 2 post-administration, but by day 35 exceeded the level of expression attained from a CMV promoter vector by four- to ninefold. Appending a portion of the CMV enhancer 5' of the UBB promoter (CMV-Ub) increased CAT expression to nearly that of the CMV promoter and expression persisted in the lung for at least 3 months, with 50% of day 2 levels remaining at day 84. In the liver, expression from the CMV-Ub hybrid promoter was sustained for 42 days. As previous studies have shown that eliminating immunostimulatory CpG motifs in pDNA vectors reduces their toxicity, we constructed a CpG-deficient version of the CMV-Ub vector expressing alpha-galactosidase A, the enzyme deficient in Fabry disease, a lysosomal storage disorder. After IN or IV administration, levels of alpha-galactosidase A from this vector were not only undiminished but increased 500% to 1500% by day 35. Our results indicate that CpG-reduced plasmid vectors containing a CMV-Ub hybrid promoter may provide the long-term expression required for a practical gene therapeutic.
Screening by colonoscopy for colonic epithelial dysplasia in inflammatory bowel disease.
Authors: A P Manning, O R Bulgim, M F Dixon, A T Axon
Journal: Gut (1987)

We report the results of a prospective study of screening for colorectal epithelial dysplasia by regular colonoscopy in patients with longstanding, extensive colitis (DET group: 112 patients, 366 colonoscopies) together with the findings in all other patients with colitis who have undergone colonoscopy in our unit (non-DET group: 77 patients, 196 colonoscopies). Thirty six DET patients had dysplasia on at least one examination: two patients with high grade dysplasia (HGD) were colonoscoped on suspicion of carcinoma, one asymptomatic patient had HGD at first colonoscopy and one patient had HGD on his sixth colonoscopy, all having carcinomas resected at surgery; the remainder had low grade dysplasia (LGD). Of the DET patients, 100 constituted an ongoing surveillance group (354 colonoscopies) in which LGD was common, being seen on at least one occasion in 33% of patients (16.4% of examinations), but HGD was noted only once with a Dukes A cancer found at surgery. Six non-DET patients had dysplasia diagnosed, this being LGD in all. Even in a carefully selected group of colitics the incidence of HGD is low, but its detection may enable the removal of a colorectal carcinoma at an early and curable stage.