tbuckley/cabot-search huggingface dataset:
Skiers, Snowboarders, and Safety Helmets
Authors: Michael D. Cusimano
Journal: JAMA (2010)

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
Abstract BSF2-1: Molecular Chaperones: Cancer Dependence and Druggability
Authors: P Workman
Journal: Cancer Research (2010)

Abstract Cancer cells live in a stressed state caused by genomic abnormalities, deregulated biochemical pathways and microenvironmental pressures. As a result they evolve, during malignant transformation and progression, a dependency on a range of molecular chaperone systems that provide essential protein folding, oncoprotein activation and anti-apoptotic functions. This chaperone dependence creates a specific vulnerability in cancer cells that is now being actively exploited in drug discovery. Our own work has focused on using a combination of genetic techniques and chemical probes (a powerful combination, see Workman P, Collins I. Probing the probes: fitness factors for small molecule tools. Chem Biol 17 561-577 2010) to enhance our understanding of the cancer biology of molecular chaperone systems. At the same time we are heavily involved in the discovery and clinical evaluation of drugs that act on these cancer-supportive molecular machines. The trail has been blazed by HSP90 inhibitors, of which at least 13 are now in clinical development. Signs of clinical activity have been seen, most notably with 17-AAG (tanespimycin) in trastuzumab-refractory, ERRB2-positive breast cancer. The new HSP90 inhibitor NVP-AUY922, which we discovered with Vernalis and is being developed by Novartis, shows good activity in breast tumour models (Eccles SA et al NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumour growth, angiogenesis, and metastasis. Cancer Res 68 2850-2860 2008). The activity of HSP90 inhibitors is self-limited by the mechanism-based activation of the protective, HSF1-dependent heat shock response. This presentation will provide an update on the discovery, development and use of HSP90 inhibitors and will describe emerging data on the identification and validation of new potential chaperone system targets, including AHA1, CDC37 and the HSP70 family (eg Powers MV, Clarke PA, Workman P. Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumour-specific apoptosis. Cancer Cell 14 250-262 2008). Molecular chaperones are overexpressed in clinical breast cancers, and in many examples their expression correlates with clinical outcome. Moreover, many oncoproteins important in breast cancer are client proteins for HSP90, including ER, PR, ERBB2, AKT/PKB/and CRAF. Thus HSP90 and other chaperone inhibitors have particular potential in breast cancer. Progress towards, and future challenges for, the potential of anti-chaperone drugs to become part of the personalized cancer medicine of the future (Yap TA, Sandhu SK, Workman P, de Bono JS. Envisioning the future of early anticancer drug development. Nat Rev Cancer 10 514-523 2010) will be highlighted. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr BSF2-1.
Retinal Vessel Alterations and Cerebral White Matter Microstructural Damage in Obese Adolescents With Metabolic Syndrome
Authors: Po Lai Yau, Minsung Kim, Aziz Tirsi, Antonio Convit
Journal: JAMA Pediatrics (2014)

IMPORTANCE Cerebral white matter (WM) damage has been reported in childhood obesity and in metabolic syndrome (MetS) but mechanisms remain unclear.OBJECTIVES To ascertain whether adolescents with MetS have retinal vessel alterations and if the anticipated reductions in retinal arteriolar diameter are associated with diminished cerebral WM microstructural integrity and to test a model for vascular etiology of the WM abnormalities. DESIGN, SETTING, AND PARTICIPANTSCross-sectional study of the brain correlates of obesity and related metabolic disease in youths.This study was conducted at the Brain, Obesity, and Diabetes Laboratory, New York University School of Medicine, New York.Thirty-nine obese adolescents with MetS and 51 matched adolescents without MetS received comprehensive endocrine, neuropsychological, retinal vessel, and diffusion tensor imaging-based cerebral WM evaluations. MAIN OUTCOMES AND MEASURESRetinal arteriolar diameter, cerebral WM microstructural integrity, waist circumference, and insulin resistance. RESULTSObese adolescents with MetS had significant reductions in retinal arteriolar diameter relative to adolescents without MetS (mean [SD] central retinal arteriolar equivalent, 182.35 [16.10] vs 198.62 [19.03] μm, respectively; P < .001).The greater the number of MetS criteria present, the greater the reduction was in retinal arteriolar diameter (β = -8.61;Δr 2 = 0.335; ΔF 1,83 = 70.79;P < .001).We found that abdominal obesity (waist circumference) was the strongest MetS component related to reductions in retinal arteriolar diameter (r p [85] = -0.661;P < .001),and importantly, for the first time to our knowledge, we demonstrated that its effect was partially mediated by comorbid insulin resistance (indirect effect = -0.1355[95% CI, -0.2471 to -0.0593]; Z = -2.56;P = .01).Consistent with our prior report of nondiabetic adolescents with MetS, we also uncovered cerebral WM microstructural damage.These subtle WM changes were associated with reductions in retinal arteriolar diameter, a proxy for cerebral microvascular health (3150 voxels or 3.15 cm 3 ; P < .001).Importantly, some of the WM regions showing lower microstructural integrity also demonstrated associations with retinal arteriolar diameter, suggesting that the observed WM pathology is likely vascular in nature. CONCLUSIONS AND RELEVANCEWe document, for the first time to our knowledge, the associations between retinal vessel alterations and subclinical WM pathology among obese adolescents with MetS.This suggests that the subtle WM pathology in adolescents with MetS may have a vascular origin.Future work should include direct assessments of cerebral microvascular health.
Flexner: 75 Years Later: A Current Commentary on Medical Education
Authors: Alberto Galofré
Journal: JAMA (1987)

Flexner's report, published in 1910, is a convenient historical marker for medical education. The report's legacy is so powerful that among medical educators the reference to "before Flexner" or "after Flexner" is almost universal. To some medical educators, this allusion may have the flavor of an era: BF or AF. The reverence for Flexner's report has not eluded Edmund Pellegrino, author of one of the book's articles. Pellegrino writes, "Any text as influential as Flexner's soon takes on a scriptural character and becomes the object of intensive exegesis. Flexner's writings have not escaped this fate." <i>Flexner: 75 Years Later</i>is a collection of six essays focused on where medical education is and where it is going. These essays were presented in the fall of 1985 at a meeting organized by the University of Medicine and Dentistry of New Jersey, Newark, to commemorate the 75th anniversary of the publication of Flexner's
Anti-microRNA-378a Enhances Wound Healing Process by Upregulating Integrin Beta-3 and Vimentin
Authors: Haoran Li, Leslie Chang, William W Du, Shaan Gupta, Azam Khorshidi, Michael Sefton, Burton B Yang
Journal: Molecular Therapy (2014)

Delayed or impaired wound healing is a major public health issue worldwide, especially in patients with diabetes mellitus and vascular atherosclerosis. MicroRNAs have been identified as key regulators of wound healing. Here, we show that miR-Pirate378a transgenic mice (and thus have inhibited miR-378a-5p function) display enhanced wound healing. Expression of vimentin and β3 integrin, two important modulators of wound healing, is markedly elevated in the transgenic mice. MiR-Pirate378a-transfected cells display greater mobility during migration assays, which was hypothesized to be due to the upregulation of vimentin and β3 integrin. Both molecules were confirmed to be targets of miR-378a, and thus their expression could be rescued by miR-Pirate378a. Overexpression of vimentin also contributed to fibroblast differentiation, and upregulation of β3 integrin was responsible for increased angiogenesis. Mice treatment with miR-Pirate378a-conjugated nanoparticles displayed enhanced wound healing. Thus, we have demonstrated that knockdown of miR-378a increased the expression of its target proteins, vimentin, and β3 integrin, which accelerated fibroblast migration and differentiation in vitro and enhanced wound healing in vivo. Delayed or impaired wound healing is a major public health issue worldwide, especially in patients with diabetes mellitus and vascular atherosclerosis. MicroRNAs have been identified as key regulators of wound healing. Here, we show that miR-Pirate378a transgenic mice (and thus have inhibited miR-378a-5p function) display enhanced wound healing. Expression of vimentin and β3 integrin, two important modulators of wound healing, is markedly elevated in the transgenic mice. MiR-Pirate378a-transfected cells display greater mobility during migration assays, which was hypothesized to be due to the upregulation of vimentin and β3 integrin. Both molecules were confirmed to be targets of miR-378a, and thus their expression could be rescued by miR-Pirate378a. Overexpression of vimentin also contributed to fibroblast differentiation, and upregulation of β3 integrin was responsible for increased angiogenesis. Mice treatment with miR-Pirate378a-conjugated nanoparticles displayed enhanced wound healing. Thus, we have demonstrated that knockdown of miR-378a increased the expression of its target proteins, vimentin, and β3 integrin, which accelerated fibroblast migration and differentiation in vitro and enhanced wound healing in vivo.
STUDIES ON THE MECHANISM OF IMMUNITY IN TUBERCULOSIS
Authors: Max B. Lurie
Journal: The Journal of Experimental Medicine (1939)

1. Tuberculous and vaccinated rabbits and guinea pigs mobilize mononuclear phagocytes at the site of a non-specific inflammation with greater rapidity than do normal animals, just as they respond to tubercle bacilli. 2. The succession of cells that characterizes inflammation in general is accelerated in allergic rabbits and guinea pigs in response to non specific irritants. 3. The pH at the site of reinfection with tubercie bacffli in immun ized rabbits and guinea pigs and at the site of a non-specific inflammation in the latter is slightly lower than in a similar site in a normal animal. 4. No constant relation was found between the mobifization of mononuclears and the hydrogen ion concentration at the site of inflammation. 5. The rate of mitotic and amitotic division of mononuclears in allergic rabbits and guinea pigs in response to non-specific irritants is greater than in normal animals. 6. Mononuclears derived from actively tuberculous or vaccinated guinea pigs exhibit greater in vitro phagocytic capacity for carbon particles than mononuclears obtained from normal animals. 7. Mononuclears of tuberculous rabbits ingest more staphylococci than the phagocytes of the same type originating from normal animals. 8. Mononuclears originating from actively tuberculous rabbits and guinea pigs exhibit greater in vitro phagocytic capacity for tuberde bacilli than mononuclears obtained from normal animals. 9. The enhancement of the phagocytic capacity for tubercie bacilli afforded mononuclears by vaccination with a bacillus of low virulence is lower, and of questionable significance. 10. The increased phagocytic activity of mononuclears derived from tuberculous or vaccinated rabbits and guinea pigs for tubercie bacilli and for non-specific particulate matter occurs in media containing sera derived from normal and from tuberculous individuals. 11. The more rapid mobilization of mononuclears by immunized animals in response to specific as well as non-specific irritants is associated with their increased physiological activity. The significance of this enhanced activity conferred by the tuberculous process on the mesenchyme cells is discussed in relation to the mechanism of immunity to tuberculosis and other phenomena.
Sequential Nonsurgical and Surgical Staging of Non-Hodgkin's Lymphoma
Authors: BRUCE A. CHABNER
Journal: Annals of Internal Medicine (1976)

The yield of specific diagnostic procedures in the staging of non-Hodgkin's lymphoma was assessed in 170 consecutive patients who were evaluated with a sequence of diagnostic procedures. Stage III or Stage IV disease was established in 141 of 170 patients (80%) by nonsurgical procedures, including lymphangiography (positive in 78%), bone-marrow biopsy (positive in 39%), percutaneous liver biopsy (positive in 21%), and peritoneoscopy-directed liver biopsy (positive in 29% of those tested). Staging laparotomy showed disease outside conventional nodal irradiation fields in 21 of 26 patients with a positive lymphangiogram, but in only three of 17 patients with a negative lymphangiogram. The yield of staging procedures was highest in patients with nodular lymphomas, only 6% of whom were Stage I or Stage II after staging, but was lowest in patients with histiocytic lymphoma, 30% of whom had localized disease. This study shows that the presence of disseminated disease can be detected in the majority of patients with non-Hodgkin's lymphoma without the use of staging laparotomy.
Impact of donor source on hematopoietic cell transplantation outcomes for patients with myelodysplastic syndromes (MDS)
Authors: Wael Saber, Corey S. Cutler, Ryotaro Nakamura, Mei-Jie Zhang, Ehab Atallah, J. Douglas Rizzo, Richard T. Maziarz, Jorge Cortes, Matt E. Kalaycio, Mary M. Horowitz
Journal: Blood (2013)
The Reliability of Clinical Methods, Data and Judgments
Authors: Lorrin M. Koran
Journal: New England Journal of Medicine (1975)

SKILLED physicians examining a patient may disagree regarding the findings. Such disagreements reflect the imperfect reliability of clinical methods and data. A decade ago, Fletcher1 urged physicians to abandon unreliable methods and stop teaching unreliable signs to their students. This paper reviews studies of physician reliability published in the last decade, together with a few studies not discussed in earlier reviews.1 2 3 4Today, consumers, insurers and government agencies, as well as physicians and their students, must become aware of the imperfect reliability of the methods and data of clinical medicine. Public Law 92–603, the Professional Standards Review . . .
Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes
Authors: Richard I.G. Holt
Journal: Diabetes Care (2004)

I commend the authors of the consensus statement in Diabetes Care for focusing our attention on the physical health of people with schizophrenia and serious mental illnesses and on the need for glucose monitoring (1). There is little consensus about the risk of diabetes in people with schizophrenia and the role of atypical antipsychotic drugs (2–4). Recently I was a member of a group of international psychiatrists and diabetologists who reviewed the evidence surrounding this issue (proceedings have been published in a supplement to the April 2004 issue of the British Journal of Psychiatry ). I was, therefore, interested to see that the conclusions published in Diabetes Care differed in some …
Vav Family GEFs Link Activated Ephs to Endocytosis and Axon Guidance
Authors: Christopher W. Cowan, Yu Raymond Shao, Mustafa Sahin, Steven M. Shamah, Michael Z. Lin, Paul L. Greer, Sizhen Gao, Eric C. Griffith, Joan S. Brugge, Michael E. Greenberg
Journal: Neuron (2005)
290. Alpha-Tocopherol Succinate (VES) Enhances Ad-mda7-Mediated Killing of Ovarian Cancer Cells
Authors: Manish Shanker, Sunil Chada, Rajagopal Ramesh
Journal: Molecular Therapy (2005)

Ovarian cancer is the second most common gynecological malignancy in the United States and is the fifth leading cause of death among women. An estimated 25,000 women will be diagnosed with ovarian cancer and 50% of these patients will die of the disease. Despite advances made in the treatment of ovarian cancer the overall long-term survival of patients have not significantly improved. Hence developing and testing of new therapeutic agents and strategies are warranted.
Short-term therapy with gatifloxacin or azithromycin prevents the acceleration of atherosclerosis after infection with Chlamydia Pneumoniaein a rabbit model but does not eradicate the organism form plaque
Authors: Heath U. Jones, Joseph B. Muhlestein, Tobin H. Lim, Jason Jensen, Robert R. Pearson, Benjamin D. Horne, Mahtab Sohrevardi, John F. Carlquist, Jeffrey L. Anderson
Journal: Journal of the American College of Cardiology (2003)
URETHROCYSTOGRAPHY IN THE MALE
Authors: JOSEPH A. HYAMS
Journal: JAMA (1933)

The lower urinary tract has been the subject of intensive investigation for the past decade, during which notable advances have been made particularly in the field of instrumental diagnosis and treatment. With increasing application, certain limitations of these procedures became apparent indicating the need for a supplementary method by which a clearer conception of form and function could be obtained. Urethrocystography fulfils this need and should be used as a part of the routine examination of patients presenting certain lesions of these organs. Although, in our hands, urethrography has proved a valuable diagnostic procedure, its scope is limited as it fails to demonstrate pathologic conditions other than those confined to the urethra and its adnexa. Cystography, while more extensively employed and better understood, also has its limitations. Because of the close anatomic and functional relationship of the posterior urethra, adnexa, vesical neck and bladder muscle, a more accurate concept of
Preventable childhood deaths in Wolverhampton.
Authors: A Moore
Journal: BMJ (1986)

A retrospective survey was undertaken of all deaths in children under 5 in the borough of Wolverhampton over the years 1976-82. Cause of death was classified in terms of preventability and possibly preventable deaths studied in more detail. Birth weight in the study group was significantly lower than that of the local population; there was no difference in ethnic origin, but there were significantly more Asian girls than Asian boys. The association between potentially preventable death and various socioeconomic indicators in the electoral wards in the borough was investigated. A significant association was found between mortality and overcrowding, lack of household amenities, unemployment, lack of car ownership, and households where the head was born in the new Commonwealth or Pakistan.
Non-specific aortitis.
Authors: C R Reddy, N R Rao, A M Anees, M R Rddy, D P Murthy, Y Ramasubbaiah
Journal: BMJ (1970)

Care of Mentally Retarded SIR,-So you think (28 February, p. 517) that Mr. Crossman was wrong to castigate the medical profession for its indifference to the mentally retarded.But suppose he had asked: "Here in this country, where there are tens of thousands of men, women, and children afflicted in this way, in which medical school is there a professor of mental retardation, a reader, even a full-time lecturer?And how is it that a medical student can go through a course of training and get hardly a reference to the subject?"What answer would you have given?But then he might well have asked himself: "What interest-before the present scandal blew its top-had I, any of my predecessors, any members of my Department, in this condition?"Would he not have got the same dusty answer?-Iam, etc.,
Renal impairment in relation to non-steroidal anti-inflammatory drugs.
Authors: J S Dixon, R Bojar, H A Bird
Journal: Annals of the Rheumatic Diseases (1988)

Renal impairment in relation to non-steroidal anti-inflammatory drugs SIR, Unsworth et al have recently shown that asymptomatic, reversible impairment of renal function is common in patients with rheumatoid arthritis (RA) receiving long term non-steroidal anti-inflammatory drug (NSAID) treat-
Successful Treatment of Solitary Toxic Thyroid Nodules with Relatively Low-Dose Iodine-131, with Low Prevalence of Hypothyroidism
Authors: DOUGLAS S. ROSS
Journal: Annals of Internal Medicine (1984)

Forty-five patients with solitary toxic thyroid adenomas received 131I (mean dose, 10.3 mCi) for treatment of hyperthyroidism and were followed for 4.9 ± 3.2 years (range, 0.5 to 13.5). Seventy-seven percent were euthyroid by 2 months, 91% by 6 months, and 93% by 1 year. Only 3 patients did not respond to a single dose of 131I, but all responded to multiple doses. Late recurrent hyperthyroidism occurred in 3 patients at 4.5, 6, and 10 years after treatment with a single dose of 131I. No patient developed clinical hypothyroidism, and none had a low serum thyroxine level associated with an elevated serum thyrotrophin level. Three patients developed minimal elevations in serum thyrotrophin levels: 1, 4, and 7. 5 years after 131I treatment, their thyrotrophin levels were 8.4, 6.2, and 9.6 µU/mL, respectively. All 3 had normal serum thyroxine levels and were clinically euthyroid. Mean serum thyroxine concentrations of all patients were unchanged between 1 and more than 9 years of follow-up. These data suggest that solitary toxic adenomas may be treated with relatively low doses of 131I (5 to 15 mCi), and that post-treatment hypothyroidism is very unusual.