tbuckley/cabot-search huggingface dataset:
294. The Histone Deacetylase Inhibitor FK228 Increases Histone Acetylation, Coxsackie Adenovirus Receptor Levels and Adenovirus Transgene Expression in Human LOX IMVI Melanoma Xenografts
Authors: Merrill E. Goldsmith, Kenneth Steadman, Alian Aguila, Michael C. Alley, William R. Waud, Susan Bates, Tito Fojo
Journal: Molecular Therapy (2006)

Adenovirus gene therapy is frequently inefficient because of low levels of coxsackie adenovirus receptor (CAR) the primary adenovirus receptor. Previously, we showed that treatment of a diverse group of cancer cell lines with the histone deacetylase inhibitor FK228 (FR901228, depsipeptide), a drug in phase II clinical trials for the treatment of peripheral and cutaneous T-cell lymphoma, caused increased CAR RNA levels and was associated with a 5-10 fold increase in adenovirus transgene expression following adenovirus infection of FK228-treated cells. Since treatment of cultured cells with 1 ng/ml FK228 caused increased acetylated histone H3, the mechanism for the FK228 effect in vitro may be through protein acetylation. This potential mechanism was also suggested because treatment with the histone deacetylase inhibitors sodium butyrate or trichostatin A also caused increased levels of CAR. Increases in CAR levels, transgene expression, and histone H3 acetylation were not found in cultured normal cells from breast, liver or kidney following similar FK228 treatment. The effect of FK228 treatment in vivo was examined in athymic mice bearing advanced-stage subcutaneous LOX IMVI human melanoma xenografts. Treatment efficacy was determined by analyzing CAR RNA levels by semi- quantitative RT-PCR analysis or by analyzing CAR protein by western blot analysis. A maximum human CAR increase of 13.6- fold (±4.3) compared to untreated xenografts was observed 24 h following i.v. injection of mice with 3.6 mg/kg FK228. By comparison, murine CAR RNA levels in livers, kidneys and lungs from the same animals remained unchanged. Xenograft protein from mice treated with 3.6 mg/kg FK228 and analyzed at 6 h following drug treatment showed no increase in CAR protein levels, however, analysis at 24 h showed a 9.2-fold (±4.8) increase in CAR levels. Based on these results xenograft-bearing mice treated with 3.6 mg/kg FK288 were given an intra-tumor injection of adenovirus carrying a GFP transgene (2E+9 VP) 24 h following FK228 administration and the xenografts were analyzed 24 h later. Analysis of RNA from the entire xenografts showed a 7.2-fold (±4.5) increase in expression from the adenovirus GFP transgene in the FK228-treated mice compared to untreated controls. In order to determine the mechanism for this effect, the levels of histone H3 acetylation in treated compared to control xenografts were analyzed. Western blot analysis of xenografts from mice showed that 6 h following treatment with 3.6 mg/kg FK228, there was an average 28.2-fold (±22.9) increase in histone H3 acetylation that remained at 20.4-fold (±12.6) 24 h following treatment. These studies suggest that the mechanism by which FK228 increases the efficiency of adenovirus gene therapy in vivo is through protein acetylation.
Treatment of mycosis fungoides with bexarotene and psoralen plus ultraviolet A
Authors: E.A. Coors, P. von den Driesch
Journal: British Journal of Dermatology (2005)

Conflicts of interest: none Sir, One of the more recent developments in the treatment of cutaneous T‐cell lymphoma (CTCL) is bexarotene, a synthetic retinoid that activates selectively the retinoid‐X‐receptor (RXR). So far, bexarotene has been used mainly as monotherapy.1 We treated three patients with mycosis fungoides (MF) in different clinical stages and variants who had all been refractory to or relapsed after at least one prior systemic therapy. In order to intensify therapy, bexarotene was combined with psoralen plus ultraviolet A (PUVA). Patient 1: A 67‐year‐old female patient was first diagnosed in 1999 with MF. For 3 years, she had refused any treatment and then presented in tumour stage (T3N1M0, IIB) with erythematous, infiltrated plaques on her whole body and several ulcerated tumours (Fig. 1a). Because of her refusal or side‐effects of other therapies, we combined PUVA with bexarotene 300 mg m−2. This led to a partial response with clearing of more than 50% of the lesions within 4 weeks (Fig. 1b). Only mild side‐effects occurred [hyperlipidaemia around 200 mg dL−1 (normal, 70–180 mg dL−1)], but did not need to be treated. The patient has been stable now for 15 months.
UK lifts lifetime ban on gay men giving blood
Authors: R. Hurley
Journal: BMJ (2011)

The ban on gay men donating blood in Great Britain is to be lifted on 7 November 2011, after new evidence, including research in the BMJ , indicated that this would not affect the safety for recipients.

Men who abstain from anal and oral sex with another man for at least one year will be eligible if they meet the other criteria for selecting donors, the Department of Health announced on 8 September. This 12 month “deferral” applies whether or not condoms were used.

“Donor selection rules are based on good evidence to maintain their credibility with donors, and this change . . . is proportionate to the current risk,” said Lorna Williamson, medical and research director of NHS Blood and Transplant, which manages donations in England and north Wales. Our priority is “to …
General practitioners' attitudes to professional reaccreditation.
Authors: S H Sylvester
Journal: BMJ (1993)

OBJECTIVE--To determine the views of general practitioners about professional reaccreditation. DESIGN--Postal questionnaire. SUBJECTS--All 278 general practitioner principals working in Cleveland. MAIN OUTCOME MEASURES--General practitioner characteristics; attitudes to reaccreditation; and views on the development, conduct, content, and format of reaccreditation. RESULTS--210 out of 278 (76%) general practitioners responded to the questionnaire. 128 (61%) agreed that general practitioners should undergo reaccreditation. 149 (72%) thought the General Medical Services Committee and local medical committees were appropriate bodies to lead its development. 120 respondents suggested that reaccreditation should be carried out by assessors appointed by the doctor9s own local medical committee. The most favoured interval between reaccreditation episodes was 10 or more years. 152 doctors thought that doctors who failed reaccreditation should be advised on education and reassessed soon afterwards. Clinical knowledge (82%), clinical skill (82%), prescribing practices (67%), standards of medical record keeping (60%), and consultation behaviour (58%) were the most popular subjects for scrutiny. 138 (67%) respondents felt that reaccreditation should be part of continuing medical education. CONCLUSION--Most general practitioners support professional reaccreditation. They believe the process should be led by the profession, be educational, and take account of a range of professional activities.
Ruptured Chordae Tendineae
Authors: R. S. O. Rees
Journal: BMJ (1967)

s hypothesis, which is also Poskanzer's,' is that early exposure to infec- ton in low risk areas prevents the later development of M.S.If this were true, how- ever, the "unexposed" immigrants should show a much higher attack rate than is found in their native lands, which seems not to be the case in Australia, Dutch Antilles, Israel, or South Africa.Further, the native-born English-speaking South Africans, as well as the Israelis, are recent arrivals, and from neither land do the current prevalence studies indicate any appreciable rate of M.S. in the parents of the subjects.Thus the evidence suggests that M.S. is " caught" in the high risk areas and brought by the migrants in a latent form into these low risk regions which provide such an invaluable human laboratory for M.S.What is the latent period can perhaps be better defined from the points raised here with the data available to Dr.
CHANGES IN CARDIAC SIZE AND FUNCTION IN CHILDREN WITH SINGLE RIGHT VENTRICLE ANOMALIES AFTER NORWOOD-RV REMODELING AFTER THE FIRST YEAR VARIES BY INITIAL SHUNT TYPE
Authors: Peter C. Frommelt, Eric Gerstenberger, James Cnota, Meryl Cohen, Jessica Gorentz, Kevin Hill, J. Blaine John, Jami Levine, Jimmy Lu, William Mahle, Rachel McCandless, Luc Mertens, Gail Pearson, Carolyn Spencer, Deepika Thacker, Ismee Williams, Pierre Wong, Jane Newburger
Journal: Journal of the American College of Cardiology (2013)
Influence of Glutathione<i>S</i>-Transferase Polymorphisms on Cognitive Functioning Effects Induced by<i>p,p</i>′-DDT among Preschoolers
Authors: Eva Morales, Jordi Sunyer, Francesc Castro-Giner, Xavier Estivill, Jordi Julvez, Nuria Ribas-Fitó, Maties Torrent, Joan O. Grimalt, Rafael de Cid
Journal: Environmental Health Perspectives (2008)

BackgroundEarly-life exposure to p,p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p′-DDT.MethodsWe used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children's Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms.Resultsp,p′-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p′-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p′-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms.ConclusionsResults indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p′-DDT exposure.
Feasibility and toxicity of high‐dose therapy (HDT) supported by peripheral blood stem cells in elderly patients with multiple myeloma and non‐Hodgkin's lymphoma: Survey from a single institution
Authors: Massimo Magagnoli, Luca Castagna, Monica Balzarotti, Barbara Sarina, Inna Timofeeva, Alexia Bertuzzi, Silvana Compasso, Andrea Nozza, Licia Siracusano, Armando Santoro
Journal: American Journal of Hematology (2003)

The aim of this retrospective study was to investigate the feasibility of high-dose therapy (HDT) followed by peripheral blood stem cell transplantation (PBSCT) in elderly patients with hematological malignancies. From April 1998 to November 2001, 40 elderly patients (defined as > or =60 years) with non-Hodgkin's lymphoma (12 patients) and multiple myeloma (28 patients) were evaluated. Seven lymphoma and one myeloma patients were in complete remission (CR), 27 in partial remission (PR), two had stable disease (SD), and three progressive disease (PD). The median age was 65 years (range 60-71). Thirty-nine patients were mobilized with chemotherapy plus granulocyte-colony stimulating factor (G-CSF) and one with G-CSF alone. Patients received HDT including melphalan alone in 32 cases or combined with other drugs in six and BEAM in two. The median number of collected CD34(+) cells was 12.4 x 10(6)/kg (range 2.0-68.9). The median number of re-infused CD34(+) cells was 9.9 x 10(6)/kg (range 2.0-68.9). All patients engrafted after PBSC and the median time to neutrophil recovery (N > 500/micro l) and platelet recovery (PLT > 20,000/micro l) was 8 days (range 5-18) and 6 days (range 5-18), respectively. Nonhematological toxicity was mild and no patient died from transplant-related toxicity (TRM). Median duration of hospitalization was 18 days (range 12-24). To date, 32 patients are alive and eight died from disease progression at a median follow-up interval of 24 months. HDT supported by PBSC is a feasible procedure in selected elderly patients, and an age of more than 60 years should not be considered a contraindication for HDT.
To the Best of Our Knowledge
Authors: Frank Cole
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The editorial by Samuel Vaisrub, MD, "To the Best of Our Knowledge, Which Is Limited at Best" (241:278, 1979), was delightful, and its point was unhappily correct. It brought to my mind that demolisher of analytical studies, "to the best of our knowledge," or "as far as we know." It goes like this: We treated so many people, and we know this many are well, and so many have died; and this many,<i>from whom we have not heard</i>, are alive and well,<i>as far as we know</i>. Someone from whom you have not heard is more likely to be dead than alive.
Diet and Diverticulitis
Authors: T. L. Cleave, G. D. Campbell
Journal: BMJ (1966)

Complications of Intrauterine Devices SIR,-Intrauterine devices are being used extensively in India.I have fitted 1,500 Lippe's loops in my practice, which consists mostly of tea-garden workers.Breast feeding is the rule in this community up to two or three years.Sometimes the amenorrhoea continues into another pregnancy.In these cases it becomes very essential to select the proper time for the insertion of the "loop."An attempt is made to fit the device four to six weeks after delivery, or soon after the
Blood Grouping, Blood Banking and Blood Transfusion
Authors: Lamar Soutter, Fred H. Allen, Charles P. Emerson
Journal: New England Journal of Medicine (1951)

HISTORICALLY, transfusion therapy is no longer an infant but a vigorous youth. Certain of its phases have already acquired definite shape, based on accumulated experience, from which little immediate change is to be anticipated. Others, particularly those involving laboratory methodology, the fractionation of donor blood and the preservation of its separated elements, are still subject to extensive modification with the expectation that many concepts and practices now current will presently be outmoded. The authors of this paper have attempted to recapitulate and summarize the more recent advances in blood banking and blood-transfusion therapy, limiting their discussion to material that is . . .
Cute Sayings, Costly Drugs
Authors: Gregory A. Thompson
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Glaxo Inc, Allen &amp; Hanburys, and Roche gave different desk calendars with "cute sayings" for each day to physicians and pharmacists this year. I was interested in the June 3,1992, physicians calendar saying underneath an advertisement for Ceftin, which read: "Pharmacists who offer generic drugs may not be doing so out of the goodness of their hearts. Although generics are less expensive, the profit margin for the pharmacist is usually greater on generic medications." This saying implies that pharmacists are less than ethical. I think it is unconscionable that the manufacturers misrepresent us in such a blatant manner. The same day I noticed this calendar saying, a patient called and asked why her Ceftin prescription, which she got for the flu, was $70 (pharmacy cost of twenty 500-mg tablets is $87.48). I suggested that she call her physician and change to ampicillin or generic cephalexin for secondary
PREFRONTAL SONIC TREATMENT (PST)
Authors: P. A. LINDSTROM, LOUIS G. MOENCH, AGNES ROVNANEK
Journal: American Journal of Psychiatry (1963)

In PST, a temporary, functional alteration of prefrontal white matter can be accomplished without anatomical changes. The results of the treatment in 258 patients with malignancies, psychoses or psychoneuroses are reported.
Principles of Ambulatory Medicine
Authors: Laura A. Offutt
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes4 May 1999Principles of Ambulatory MedicineLaura A. Offutt, MDLaura A. Offutt, MDThomas Jefferson University Hospital, Philadelphia, Pennsylvania. (Offutt)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-9-199905040-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 5th edition. Barker LR, Burton JR, Zieve PD; eds. 1660 pages. Baltimore: Williams & Wilkins; 1999. $109.00. ISBN 068330352X. Order phone 800-638-0672.Field of medicine: General outpatient adult medicine.Format: Hardcover book.Audience: Office-based internists, family practitioners caring for adult patients, nurse practitioners, physicians' assistants, medical students, and physicians-in-training.Purpose: To provide guidance in the evaluation, management, and long-term course of clinical problems seen in the ambulatory setting and to aid the reader in recognizing problems that require referral to specialists or inpatient management.Content: Most of the sections of the book are grouped by organ system (psychiatry, allergy and ... Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. (Offutt) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 May 1999Volume 130, Issue 9Page: 788KeywordsClinical epidemiologyDermatologyNursesOral diseasesOtorhinolaryngologyOutpatientsPatientsPulmonary medicineRenal diseasesUrology ePublished: 15 August 2000 Issue Published: 4 May 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Evidence for HL-A-linked genes in "juvenile" diabetes mellitus.
Authors: A G Cudworth, J C Woodrow
Journal: BMJ (1975)

HL-A typing of 150 patients who had developed diabetes mellitus by the age of 30 years showed a significant association with HL-A 8 and W 15. The HL-A genotypes were determined in 17 families in which two or more siblings had this type of diabetes. The zygotic assortment of HL-A haplotypes was found to be significantly disturbed from the expected random pattern, with a reduction in the number of siblings showing no identical haplotypes and an appreciable increase in the number with both haplotypes identical. This appears to be most consistent with the presence of a gene or genes pre-disposing to this type of diabetes at a locus closely linked to the HL-A chromosomal loci. This locus appears to have a fundamental role in the susceptibility to juvenile diabetes.
International Comparisons of Medical-Care Utilization
Authors: Kerr L. White, Dragana Andjelkovic, R. J. C. Pearson, John H. Mabry, Alan Ross, O. K. Sagen
Journal: New England Journal of Medicine (1967)

TO assess the influence of the organization and financing of health services on their utilization in general populations, it is desirable to choose contrasting regional or national systems. Before even this can be attempted, it is essential to estimate the extent to which a dependent variable such as utilization can be simultaneously and comparably measured in different communities. This feasibility study attempts to ascertain whether valid and comparable data bearing on the use of doctors' and nurses' services and on hospitalization among defined populations during a given time can be collected simultaneously in several settings with standardized procedures.This is . . .
Protein kinase LKB1 promotes RAB7-mediated neuropilin-1 degradation to inhibit angiogenesis
Authors: Imoh S. Okon, Kathleen A. Coughlan, Cheng Zhang, Cate Moriasi, Ye Ding, Ping Song, Wencheng Zhang, Guangpu Li, Ming-Hui Zou
Journal: Journal of Clinical Investigation (2014)

After internalization, transmembrane receptors (TMRs) are typically recycled back to the cell surface or targeted for degradation. Efficient TMR trafficking is critical for regulation of several processes, including signal transduction pathways, development, and disease. Here, we determined that trafficking of the angiogenic receptor neuropilin-1 (NRP-1) is abrogated by the liver kinase B1 (LKB1), a serine-threonine kinase of the calcium calmodulin family. We found that aberrant NRP-1 expression in tumor cells from patients with lung adenocarcinoma is associated with decreased levels of LKB1. In cultured lung cells, LKB1 accentuated formation of a complex between NRP-1 and RAB7 in late endosomes. LKB1 specifically bound GTP-bound RAB7, but not a dominant-negative GDP-bound form of RAB7, promoting rapid transfer and lysosome degradation of NRP-1. siRNA-mediated depletion of RAB7 disrupted the transfer of NRP-1 to the lysosome, resulting in recovery of the receptor as well as increased tumor growth and angiogenesis. Together, our findings indicate that LKB1 functions as a RAB7 effector and suppresses angiogenesis by promoting the cellular trafficking of NRP-1 from RAB7 vesicles to the lysosome for degradation. Furthermore, these data suggest that LKB1 and NRP-1 have potential as therapeutic targets for limiting tumorigenesis.
TREAD adds little to the evidence
Authors: S. Pilling, I. Anderson
Journal: BMJ (2012)

The TREAD trial claims that physical exercise does not improve mood.1 The trial, however, has serious limitations.

The National Institute for Health and Clinical Excellence recommends structured group physical activity to treat subthreshold and mild-moderate depression. TREAD did not evaluate this intervention but aimed to increase physical activity, through the use of physical activity facilitators, to such a level that it improves …
Joint Effect of Insulin-Like Growth Factors and Mutagen Sensitivity in Lung Cancer Risk
Authors: X. Wu
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: We hypothesize that accumulation of genetic damage is dependent on an individual's intrinsic carcinogen sensitivity and on various humoral factors (e.g., insulin-like growth factors [IGFs]) that enhance proliferation, resistance to apoptotic cell death, and clonal outgrowth of genetically damaged cells. We tested this hypothesis by determining whether proliferation potential and genetic instability are associated with the risk of lung cancer. Methods: In a study of 183 lung cancer patients and 227 matched control subjects, we examined the joint effects of latent genetic instability (measured as mutagen sensitivity) and elevated proliferation potential (assessed by measuring IGFs) in lung cancer risk. Levels of IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in plasma were measured by use of immunoassay kits. Mutagen sensitivity was assessed by quantitating bleomycin- and benzo[a]pyrene diol epoxide (BPDE)-induced chromatid breaks in peripheral blood lymphocyte cultures. Results: Although not statistically significant, the mean levels of IGF-I and the molar ratio of IGF-I/IGFBP-3 were higher in patients with advanced or poorly differentiated disease than in patients with early or well-differentiated disease. Variation in IGFs was not associated with any specific histologic type or tumor stage. High levels of IGF-I and enhanced mutagen sensitivity were individually associated with increased risk of lung cancer: odds ratio (OR) of 2.13 (95% confidence interval [CI] = 1.20–3.78) for IGF-I, 2.50 (95% CI = 1.49–4.20) for bleomycin sensitivity, and 2.95 (95% CI = 1.72–5.06) for BPDE sensitivity. The OR was statistically significantly elevated to 8.88 for both higher IGF-I and bleomycin sensitivity (95% CI = 3.67–21.50) and to 13.53 for higher IGF-I and BPDE sensitivity combined (95% CI = 4.48–40.89). With all three risk factors considered together, the OR was 17.09 (95% CI = 4.16–70.27). High levels of IGFBP-3 alone were associated with reduced lung cancer risk: OR = 0.59 (95% CI = 0.33–1.05). Conclusions: Our data suggest that individuals with genetic instability and higher proliferation potential are at enhanced risk for lung cancer.