tbuckley/cabot-search huggingface dataset:
Indications for PSA Testing
Authors: Michael J. Barry
Journal: JAMA (1997)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Anti-tumor targeted drug delivery systems mediated by aminopeptidase N/CD13
Authors: Xun Wang, Bin Wang, Qiang Zhang
Journal: Acta Pharmaceutica Sinica B (2011)

Aminopeptidase N (APN)/CD13 is a transmembrane glycoprotein, which is overexpressed on tumor neovascular endothelial cells and most tumor cells, where it plays an important role in tumor angiogenesis. Peptides containing the Asn-Gly-Arg (NGR) motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells. This article reviews the literature and recent developments related to APN/CD13, its role in tumor growth and some anti-tumor drug delivery systems containing NGR peptides designed to target APN/CD13.
Radiographic Anatomy of the Coronary Arteries
Authors: C. M Oakley
Journal: BMJ (1976)

was subjected to analysis by laboratory and clinical criteria.Not surprisingly in view of the small numbers of patients and their presumed heterogeneity this study presents little in the way of definitive evidence on the nature and causation of this group of con- ditions.It contains, however, a good review of the literature and throws out suggestions for further work.
FD&amp;C Yellow No. 6: Condensation of the Carcinogenesis Bioassay Technical Report
Authors: James Huff
Journal: Environmental Health Perspectives (1982)

desserts, sherbets, carbon- ated beverages, candies, cereals, jams, pickles, smoked fish, puddings, medicinals (liquids, tablets, and capsules), toothpastes, hair rinses, and other foods, drugs, and cosmetics.
ACUTE CHANGES IN CARDIAC OUTPUT FOLLOWING A MITRACLIP PROCEDURE ARE A POWERFUL PREDICTOR OF CLINICAL OUTCOMES
Authors: Wen–Loong Yeow, Takashi Matsumoto, Robert Siegel, Asma Hussaini, Mamoo Nakamura, Moody Makar, Amin Manuchehry, Rehan Kanji, Alfredo Trento, Saibal Kar
Journal: Journal of the American College of Cardiology (2013)
Nestle abides fully to WHO code on baby milk
Authors: R F Claydon
Journal: BMJ (1995)

EDITOR,—Andrew Radford justifies his attack on the British Paediatric Association by giving a reference to a booklet produced by the International Baby Food Action Network, Breaking the Rules 1994.1 2 He adopts his usual stance of assuming that if his organisation makes an allegation then the rest of the world must believe it to be true, even though many …
Maternal Thyroid Function is the Major Determinant of Amniotic Fluid 3,3′,5′-Triiodothyronine in the Rat
Authors: Mohamed M. El-Zaheri, Apostolos G. Vagenakis, Lee Hinerfeld, Charles H. Emerson, Lewis E. Braverman
Journal: Journal of Clinical Investigation (1981)

3,3′,5′-triiodothyronine, (rT3), is easily measured in human amniotic fluid (AF) during the second and third trimesters. To determine if AF rT3 levels are maintained by either maternal or fetal thyroid function, or both, models of fetal hypothyroidism (FH), maternal hypothyroidism (MH), and combined maternal and fetal hypothyroidism (MFH) were developed in pregnant rats. Hormone analyses of maternal and fetal serum and AF were performed at term. Thyroxine (T4) and 3,3′,5-triiodothyronine (T3) were not detectable in the sera and AF of term fetuses in all groups. MFH rats were prepared by administration of methimazole to the dams, and in some experiments, by maternal thyroidectomy and a low iodine diet as well. In the MFH groups from the three experiments serum thyrotropin (TSH) was markedly elevated in the dams and in the fetuses. FH rats were prepared by administering T4 by various routes to dams treated according to the MFH protocols and serum TSH was elevated in fetal serum. Analysis of FH maternal serum T4, T3, and TSH concentrations suggested mild maternal hyperthyroidism or hypothyroidism depending upon the schedule of T4 administration. The MH groups were prepared by maternal thyroidectomy and in all experiments the fetuses had normal serum TSH concentrations. The degree of maternal hypothyroidism in the MH and MFH groups was equivalent. The mean concentration of AF rT3 in normal rats in three experiments was 28.4±2.5 ng/dl (±SEM). In the three experiments, AF rT3 was undetectable or markedly reduced in the MH and MFH rats and was normal in the FH rats. These results in the amniotic fluid could not be explained by transfer of rT3 from fetal serum to the AF because fetal serum rT3 concentrations in these various models did not correlate with AF rT3 concentration. Furthermore, infusion of large doses of rT3 in MFH dams resulted in a 35-fold elevation in maternal serum rT3 concentration, a twofold elevation in fetal serum rT3 concentration, and only a minimal increase in AF rT3. These studies demonstrated that, in the rat, the maternal thyroid has the dominant role in maintaining AF rT3, whereas little effect of fetal thyroid status on AF rT3 could be demonstrated. Transfer of maternal rT3 or of fetal rT3 derived from maternal T4 to the AF do not appear to be the mechanisms whereby the maternal thyroid maintains AF rT3.
Platelet storage results in a redistribution of glycoprotein Ib molecules. Evidence for a large intraplatelet pool of glycoprotein Ib.
Authors: A D Michelson, B Adelman, M R Barnard, E Carroll, R I Handin
Journal: Journal of Clinical Investigation (1988)

Platelet membrane glycoprotein (GP) Ib contains receptor for von Willebrand factor and thrombin. Its proteolytic fragment, glycocalicin, circulates in normal plasma. In this study, storage of platelet concentrates for 5 d resulted in a 221% increase in plasma glycocalicin (1.3 times the total amount of glycocalicin present on the surface of all platelets), an 8% overall increase in platelet surface GPIb, and the appearance of a surface GPIb-negative subpopulation of platelets. Total platelet GPIb content of fresh washed platelets, determined by gel electrophoresis and immunoassay of Triton X-100 lysates, averaged 159,740 molecules per platelet. There were 36,360 surface GPIb molecules per platelet, determined by immunoassay of the supernatant of fresh washed platelets whose surface GPIb had been completely plasmin-cleaved. In summary, these studies provide evidence for (a) a redistribution of GPIb molecules with platelet storage, and (b) a large intraplatelet pool of GPIb (approximately threefold larger than the platelet surface pool of GPIb).
Reasons why doctors who perform well as doctors may fail the MRCGP clinical skills assessment exam
Authors: R. A. Knight
Journal: BMJ (2013)

Many of my GP colleagues spend over half of their time consulting in Gujarati, Urdu, Hindi, and Punjabi. I work with doctors who fail the clinical skills assessment exam, many of whom are deemed to be good doctors in their work place assessments and some of whom have been offered jobs in their training practice. I think that the evidence indicates that the clinical skills assessment exam is reliable, but why are good doctors failing, particularly international medical graduates? …
762. Inhibition of HIV-1 Replication by Simian Intrinsic Restriction Factors, TRIM5alpha and APOBEC3G
Authors: Ryuta Sakuma, JoshA. Noser, Yasuhiro Ikeda
Journal: Molecular Therapy (2006)

The gene therapy approach for AIDS using therapeutic sequences that block viral replication has been extensively studied. The inhibitory effects of HIV-1 replication by anti-HIV ribozymes, decoys or antisense constructs are rather mild. Although sequence-specific degradation of viral mRNA by siRNA constructs strongly inhibit HIV-1 replication, the emergence of escape mutants with few mutations in the siRNA target region can avoid the antiviral activity of viral siRNA. Recently, two intrinsic cellular factors, which control HIV-1 permissivity in primate cells, were identified as TRIM5alpha and APOBEC3 proteins. Old World monkey TRIM5alpha targets incoming HIV-1 viral capsid (CA) and blocks viral reverse transcription, whereas the APOBEC3 family hypermutate or degrade viral sequences. Here we examined the impacts of simian TRIM5alpha and APOBEC3G expression on HIV-1 replication. First we examined the effects of HIV-1 Gag/CA substations on simian TRIM5alpha-mediated restriction in human cells. We demonstrated that both rhesus (rh)- and African green monkey (agm)-derived TRIM5alpha could efficiently restrict HIV-1 vectors with divergent, naturally occurring Gag/CA substitutions from different HIV-1 subtypes. HIV-1 vectors with H87Q CA substitution, which are less sensitive to Lv1 restriction in monkey cells, were also blocked by the simian TRIM5alpha. Human T cells genetically engineered to express rh- or agm-TRIM5alpha could block or delay HIV-1 replication and were more protected from viral cytopathic effects. Although agm-APOBEC3G expression alone could only transiently suppress HIV-1 replication, co-expression of agm-APOBEC3G and agm-TRIM5a significantly enhanced the antiviral effects of agm-TRIM5a and successfully blocked the virus replication for more than 5 weeks. Therefore, the intrinsic restriction factors are promising candidates as therapeutic genes for AIDS gene therapy.
Broad-β Disease (Type III Hyperlipoproteinemia) in a Large Kindred
Authors: WILLIAM R. HAZZARD
Journal: Annals of Internal Medicine (1975)

The inheritance of broad-β disease (as specified by a type III lipoprotein pattern) has remained an enigma. Previous reports have variously implicated a single gene (autosomal dominant mode), a double dose of a single gene (autosomal recessive), two separate genes (mixed heterozygosity), or multiple genes (polygenic inheritance). The present study of a single, large kindred of 108 members spanning 4 generations provides evidence for an autosomal dominant mode, since at least 1 member of the first generation pair was normal, at least 5 of their 9 children had type III patterns, and at least 2 of these (whose spouses were normal) transmitted this pattern to their offspring. The findings also suggest that in this kindred the common occurrence of hypertriglyceridemia (in a type IV pattern) may represent either a variable phenotypic expression of the gene for broad-β disease or the coexistence of a second, independent genetic lipid disorder.
Commentary: Outcome measures were flawed
Authors: G. C. Ebers
Journal: BMJ (2010)

Interferons were introduced for multiple sclerosis in the early 1990s, after US-Canadian trials showed effects on clinical relapse rate and magnetic resonance imaging (MRI) spots, which were taken as surrogate outcomes for disability.1 The drug companies who marketed the interferons, and later glatiramer acetate, were given extended patent protection under the Orphan Drug Act. Under the terms of this act surrogate markers of response to treatment can be relied on if experts certify their validity. The lack of data on hard outcomes of disability, such as the need to use a stick or wheelchair, was accepted because multiple sclerosis is a 30-40 year disease, with only half of those affected becoming moderately disabled in a decade, and keeping trials intact beyond a few years proved difficult.

Many specialists thought the visually obvious spots on MRI “were the disease.” As a result MRI scanning soon became indispensable for multiple sclerosis trials and individual high profile MRI centres capitalised on lucrative contracts with industry. Over the next two decades, little effort was made to validate the suppression of MRI spots against hard disease outcomes. Amid the enthusiasm for short term MRI monitoring of the impact of interferons, their lack of impact on long term disability (despite …
Health authorities face big payouts after ombudsmans ruling
Authors: A. Gulland
Journal: BMJ (2003)

Thousands of patients needing long term care could win compensation after a report by the health service ombudsman found that patients and their families had been wrongly forced to pay for their care.

The ombudsman, Ann Abraham, said health authorities should look at all cases since 1996 and review the criteria used since then to determine whether patients were eligible for funding. She said that authorities should “make efforts to remedy any consequent financial injustice to patients” if these criteria were applied wrongly.

She said that health authorities should also ensure that they …
Clinical experience with topical calcitriol (1,25-dihydroxy-vitamin D3) in psoriasis
Authors: L. Kowalzick
Journal: British Journal of Dermatology (2001)

The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 μg g−1 ointment (Silkis ointment®, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short-contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8-week period; however, the combination had a radiation dose-sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice-daily betamethasone, thereby achieving a corticosteroid-sparing effect. Finally, two studies confirm that calcitriol 3 μg g−1 ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound.
Gemcitabine and Cytosine Arabinoside Cytotoxicity: Association with Lymphoblastoid Cell Expression
Authors: Liang Li, Brooke Fridley, Krishna Kalari, Gregory Jenkins, Anthony Batzler, Stephanie Safgren, Michelle Hildebrandt, Matthew Ames, Daniel Schaid, Liewei Wang
Journal: Cancer Research (2008)

Abstract Two cytidine analogues, gemcitabine (dFdC) and 1-β-d-arabinofuranosylcytosine (AraC), show significant therapeutic effect in a variety of cancers. However, response to these drugs varies widely. Evidence from tumor biopsy samples shows that expression levels for genes involved in the cytidine transport, metabolism, and bioactivation pathway contribute to this variation in response. In the present study, we set out to test the hypothesis that variation in gene expression both within and outside of this “pathway” might influence sensitivity to gemcitabine and AraC. Specifically, Affymetrix U133 Plus 2.0 GeneChip and cytotoxicity assays were performed to obtain basal mRNA expression and IC50 values for both drugs in 197 ethnically defined Human Variation Panel lymphoblastoid cell lines. Genes with a high degree of association with IC50 values were involved mainly in cell death, cancer, cell cycle, and nucleic acid metabolism pathways. We validated selected significant genes by performing real-time quantitative reverse transcription-PCR and selected two representative candidates, NT5C3 (within the pathway) and FKBP5 (outside of the pathway), for functional validation. Those studies showed that down-regulation of NT5C3 and FKBP5 altered tumor cell sensitivity to both drugs. Our results suggest that cell-based model system studies, when combined with complementary functional characterization, may help to identify biomarkers for response to chemotherapy with these cytidine analogues. [Cancer Res 2008;68(17):7050–8]
Front Line, Sources of Conflict All Too Close for US Military Physicians in Divided Korea
Authors: Virginia S. Cowart
Journal: JAMA (1989)

SEATED IN COMFORT in the General's Mess—chatting about sports— these Americans could have been any of the thousands of visitors to the 1988 Olympic Games in Seoul, South Korea, with no more in mind than whether the sunshine would hold for the track events. However, the Seoul area is home to some 41 000 US military personnel who live as close as anyone in the world to what could be called a "front line." The 38th parallel that marks the border with North Korea is relatively close to Seoul (but a drive of about an hour). Some of the conversational participants are US Army physicians who would be called upon to treat the wounded if that front line became a battle line. About a quarter of the 70 million South Koreans live in Seoul, an ancient city that was largely destroyed during the Korean conflict. However, about 60% of Seoul's
Management of Newly Diagnosed HIV Infection
Authors: Judith Feinberg, Susana Keeshin
Journal: Annals of Internal Medicine (2017)

No field in medicine has moved as swiftly as HIV/AIDS over the past 35 years. Because of the rapid turnover of key information, this In the Clinic focuses on essential principles of care for newly diagnosed adults with HIV-1 infection and how to prevent infection in persons at risk. To ensure continued usefulness, future directions in therapy and how to access updated information on a continuous basis are emphasized.
Bona Fide Genetic Associations with Bone Mineral Density
Authors: Joel N. Hirschhorn, Luigi Gennari
Journal: New England Journal of Medicine (2008)

Osteoporosis is a common skeletal disorder characterized by compromised bone strength and increased bone fragility, affecting up to 40% of postmenopausal women and 15% of men.1 Its clinical significance lies in the occurrence of osteoporotic fractures — most commonly involving the forearm, the vertebral bodies, and the hip — with considerable morbidity, mortality, and cost to the individual and the community.2 Many factors, including age, menopausal status, smoking, physical activity, diet, coexisting diseases, and pharmacologic treatments, influence the risk of osteoporosis, but one of the most clinically important risk factors is a family history of the disorder. As in other . . .
Monophosphoryl lipid A (MPL<sup>®</sup>)* promotes allergen‐induced immune deviation in favour of Th1 responses
Authors: F. Puggioni, S. R. Durham, J. N. Francis
Journal: Allergy (2005)

Background: Monophosphoryl lipid A (MPL ® ) is a nontoxic derivative of the lipopolysaccharide (LPS) of Salmonella minnesota R595. MPL has been used as an adjuvant in grass and tree pollen vaccines for the treatment of seasonal allergic rhinitis. Little is known about the influence of MPL on cellular responses to allergens in man. We therefore studied the effects of MPL in vitro on peripheral blood mononuclear cells (PBMC) obtained from patients with grass pollen hay fever. Methods: The PBMCs from 13 subjects were cultured with grass pollen Phleum pratense extract (0, 2 and 20 μ g/ml) and MPL (0 and 10 μ g/ml; defined as an optimal concentration in preliminary studies) and after 6 days proliferative responses were measured by thymidine incorporation and cytokine production by enzyme‐linked immunosorbent assay (ELISA). Results: Proliferative responses were unaffected by the presence of MPL whereas MPL induced a significant increase in allergen‐induced interferon (IFN)‐ γ production [allergen alone, 645 ± 466 pg/ml (mean ± SE) vs allergen + MPL, 3232 ± 818 pg/ml; P &lt; 0.001]. In addition, there was a significant decrease in interleukin (IL)‐5 production (4307 ± 1030 pg/ml vs 2997 ± 826 pg/ml; P &lt; 0.01). Although MPL alone could induce modest increases in IL‐10 production, MPL did not influence the production of this cytokine in allergen‐stimulated cultures. Addition of neutralizing antibody against IL‐12 resulted in 95% inhibition of MPL‐induced IFN‐ γ production. Depletion of monocytes from the culture system abrogated the effects of MPL on elevated cytokine production. Conclusions: In summary, use of MPL with grass pollen extract results in immune deviation of allergen‐induced peripheral Th2‐cell responses in favour of ‘protective’ Th1 responses in an IL‐12 and monocyte‐dependent fashion.
<i>C‐MYC</i> rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene <i>ALO17/C‐MYC</i>
Authors: Hiroshi Moritake, Hidemi Shimonodan, Kousuke Marutsuka, Sachiyo Kamimura, Hitomi Kojima, Hiroyuki Nunoi
Journal: American Journal of Hematology (2010)

Anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma (ALCL) is usually associated with a favorable prognosis. We describe an 11-year-old girl patient with ALK positive ALCL bearing t(2;5)(p23;q35) and t(8;17)(q24;q25) translocations who had an aggressive clinical course despite various combinations of intensive chemotherapy. Southern blot analysis identified C-MYC rearrangement. Immunohistochemistry and Northern and Western blot analyses revealed cmyc overexpression. A new fusion between ALO17 (ALK lymphoma oligomerization partner on chromosome 17) and C-MYC was identified by the 50-rapid amplification of cDNA ends. This new fusion may have possibly provoked the poor prognosis in this patient with ALK positive ALCL, and C-MYC rearrangement may indicate poor prognosis in ALCL.
OCULAR TENSION; PERIPHERALISM; FOREIGN CLINICS.
Authors: WILLIAM B. MEANY
Journal: JAMA (1899)

Much as it is to be regretted, there still remains much doubt concerning important etiologic and pathologic factors of intraocular tension, and notwithstanding certain pathologic conditions are pretty constantly found in glaucomatous affections, the problem is yet to be solved. Glaucoma is of even more importance than "sympathetic" ophthalmitis,<sup>1</sup>because it appears to be little, if any, better understood, and still more on account of its far wider prevalence and equally fatal consequences to sight when uncontrolled. It is not my deliberate purpose to condemn unreservedly the conventional treatment, or to call any especial attention to the chaos that has always reigned in these branches of disease, nor to harbor any fancy or vain imaginations against the true spirit of science, to attempt the promulgation of a "complete system" by making "new knowledge" fit into the old; I will therefore endeavor to confine my remarks to some observations of