tbuckley/cabot-search huggingface dataset:
HOXB13 May Predict Response to Neoadjuvant Letrozole in Patients with Estrogen Receptor-Positive Breast Cancer.
Authors: X. Ma, R. Bandaru, M. Letzkus, P. Philips, J. Barrett, M. Erlander, M. Goetz, D. Sgroi, H. Gardner, J. Baselga
Journal: Cancer Research (2009)

Abstract Background. Third generation aromatase inhibitors (AIs) have been shown to be superior to tamoxifen in multiple randomized clinical trials and become the new standard of treatment for postmenopausal women with early or advanced endocrine-sensitive breast cancer. It is thus important to identify biomarkers predicting resistance to AIs so that alternative therapeutic options can be employed. A two gene expression index, HOXB13:IL17BR, and HOXB13 in particular, has been shown to be a negative predictor of clinical benefit from tamoxifen. It is unclear whether HOXB13:IL17BR or HOXB13 is also predictive of AI therapy.Methods. We performed a retrospective analysis of a phase II randomized neoadjuvant study of everolimus+letrozole vs. placebo+letrozole in patients with estrogen receptor-positive breast cancer. Total RNA was extracted from frozen tissue biopsies taken either prior to treatment or after 15 days of treatment. HOXB13:IL13BR and a molecular grade index (MGI) were measured in 107 pre-treatment samples and 111 samples after 15 days of treatment. Antiproliferative response as defined by a ln[Ki767] &amp;lt;1 at day 15 in the samples analyzed was correlated with these gene expression indices.Results. In the placebo+letrozole treatment arm, the antiproliferative response rate was 30% (14/47). Using a pre-specified cutpoint of 0.06, the response rate was 40% for low HOXB13:IL17BR patients, compared to 12% for high HOXB13:IL17BR patients (p=0.05). In the everolimus+letrozole arm, the antiproliferative response rate in the samples analyzed was 55% (33/60), and the response rates for low and high HOXB13:Il17BR patients were 70% and 37% (p=0.02), respectively. When examined separately, high HOXB13 expression was significantly associated with nonresponse to therapy (everolimus+letrozole arm, p=0.02; placebo+letrozle arm, p=0.03), but IL17BR was not (everolimus+letrozole arm, p=0.6; placebo+letrozle arm, p=0.88). As expected, we observed a significant correlation between MGI and Ki67 staining (Spearman r=0.67, p&amp;lt;0.0001).Conclusions. High HOXB13:IL17BR index and high HOXB13 expression may identify a possible subset of patients with estrogen receptor-positive tumor that could be less responsive to aromatase inhibitors such as letrozole. Furthermore, use of MGI may enable rapid assessment of antiproliferative response by fine needle aspiration. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2120.
CN-01 * EVIDENCE FOR ACTIVE GLYCOLYSIS IN THE WHITE MATTER OF AN ADULT SURVIVOR OF A PEDIATRIC BRAIN TUMOR WITH LONG-TERM TREATMENT-RELATED BRAIN INJURY
Authors: R. J. Brown, S. O'Neil, J. L. Finlay, S. Bluml
Journal: Neuro-Oncology (2014)

BACKGROUND: Mitigating long-term treatment-related effects in survivors of pediatric brain tumors is hampered, in part, by a long clinical prodrome, ill-defined diagnostic criteria, and reliance on indirect observations of the brain. Recently, oxidative stress has been associated with several forms of brain injury. The brain's response to increased oxidative stress includes, in part, a shift from oxidative phosphorylation to glycolysis for its ATP production. We investigated if lactate, a product of glycolysis, was increased in the brain of a patient with treatment-related brain injury via magnetic resonance spectroscopy (MRS). METHODS: A 24 year-old patient treated for a mixed germ cell tumor at the age of 17 with a standard protocol including high-dose chemotherapy, hematopoietic progenitor cell rescue, and irradiation developed evidence of treatment-related brain injury 6 years later. MRS was performed on abnormal-appearing white matter before and serially over 100 minutes after oral administration of 13Carbon-labeled glucose. RESULTS: MRS of abnormal-appearing parietal white matter demonstrated inverted choline:creatine ratio, decreased levels of N-acetyl aspartate, and elevated levels of lactate when compared to historical age-matched controls. Subsequent spectra obtained over the course of 100 minutes following administration of 13Carbon-labeled glucose demonstrated a linear decrease in the concentration of native 12Carbon lactate (slope = -0.003, R2 = 0.51, p = 0.006). CONCLUSIONS: The metabolite profile of the abnormal white matter was not consistent with a non-metabolically active pool or necrosis. The real-time decrease of observed 12Carbon lactate indicated the active production of 13Carbon lactate following oral 13Carbon-labeled glucose administration. To our knowledge, this is the most direct evidence of active glycolysis in the abnormal-appearing white matter in a survivor of a pediatric brain tumor with treatment-related brain injury. Thus, the detection of active glycolysis by increased concentrations of lactate may indicate a compensatory mechanism of neurons under increased oxidative stress and serve as a potential biomarker for this injury.
Paleolithic Nutrition
Authors: S. Boyd Eaton, Melvin Konner
Journal: New England Journal of Medicine (1985)

HUMANITY has existed as a genus for about 2 million years, and our prehuman hominid ancestors, the australopithecines, appeared at least 4 million years ago (Table 1). This phase of evolutionary history made definitive contributions to our current genetic composition, partly in response to dietary influences at that time. The foods available to evolving hominids varied widely according to the paleontological period, geographical location, and seasonal conditions, so that our ancestral line maintained the versatility of the omnivore that typifies most primates. Natural selection has provided us with nutritional adaptability; however, human beings today are confronted with diet-related health problems . . .
SOUND PERCEPTION IN DEAF MUTES
Authors: John Dutton Wright
Journal: JAMA (1918)

the implication that the "full therapeutic value" of salicylates cannot readily be attained by their oral use.Still more astonishing is the following claim : "Venosal is a combination carrying the true salicylates (sodii) in doses much larger than given by mouth.With this preparation given intravenously, there is no nausea or disagreeable digestive after-effects, tinnitus aurium, or the accumulating effects of the drug; yet the specific action of the salicylates seems to be increased many-fold, according to reports received."
A20 Is Dynamically Regulated in the Heart and Inhibits the Hypertrophic Response
Authors: Stuart A. Cook, Mikhail S. Novikov, Youngkeun Ahn, Takashi Matsui, Anthony Rosenzweig
Journal: Circulation (2003)

Nuclear factor (NF)-kappaB signaling has been implicated in cardiomyocyte hypertrophy. Here, we determine the cardiac regulation and biological activity of A20, an inhibitor of NF-kappaB signaling.Mice were subjected to aortic banding, and A20 expression was examined. A20 mRNA upregulation (4.3+/-1.5-fold; P<0.05) was detected 3 hours after banding, coinciding with peak NF-kappaB activation. A20 was also upregulated in cultured neonatal cardiomyocytes stimulated with phenylephrine or endothelin-1 (2.8+/-0.6- and 4+/-1.1-fold, respectively; P<0.05), again paralleling NF-kappaB activation. Infection of cardiomyocytes with an adenoviral vector (Ad) encoding A20 inhibited tumor necrosis factor-alpha-stimulated NF-kappaB signaling with an efficacy comparable to dominant negative inhibitor of kappa-B kinase beta (dnIKKbeta). Ad.dnIKKbeta-infected cardiomyocytes exhibited increased apoptosis when they were serum starved or subjected to hypoxia-reoxygenation, whereas Ad.A20-infected cardiomyocytes did not. Expression of Ad.A20 inhibited the hypertrophic response in cardiomyocytes stimulated with phenylephrine or endothelin-1.A20 is dynamically regulated during acute biomechanical stress in the heart and functions to attenuate cardiac hypertrophy through the inhibition of NF-kappaB signaling without sensitizing cardiomyocytes to apoptotic cell death.
Richard (“Dick”) Vernon Sykes
Authors: Ian Sykes
Journal: BMJ (2006)

​FormerFormer general practitioner Borrowash, Derby, and orthopaedic clinical assistant Derby Royal Infirmary and Derby Children's Hospital (b 1924; q Manchester 1948), died from peritonitis on 23 July 2006.



Figure 1



After national service and some time in orthopaedics Dick entered general practice in south east Derbyshire in 1957. He took on two orthopaedic clinical assistantships in Derby in 1959 to maintain his orthopaedic interest. Dick retired from general practice in 1989, but continued his hospital posts, finally retiring in 1998, having completed 50 years' service for the NHS. He was also a keen golfer, both playing for and captaining Nottinghamshire. After retirement he developed heart failure but still lived life to the full. He leaves a wife, Sheila; three children; and six grandchildren.
Sex Hormones and DHEA-SO4 in Relation to Ischemic Heart Disease Mortality in Diabetic subjects: The Wisconsin Epidemiologic Study of Diabetic Retinopathy
Authors: Steven M Haffner, Scot E Moss, Barbara EK Klein, Ronald Klein
Journal: Diabetes Care (1996)

Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD.We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject).In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may be associated with worse IHD risk factors.This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.
<i>Children’s Story (Water Dreaming for Two Children)</i>
Authors: Thomas B. Cole
Journal: JAMA (2015)

Life in the Northern Territory of Australia is sustained by sedimentary aquifers accessed by remote wells, caves, and soaks. The indigenouspeople of theNorthern Territory have survived for millennia in this arid country by knowing how to find sources of water and by keeping the locations of water sources to themselves. These locations are often well hidden—a cave entrance may be covered with branches, and a usable soak may be no more than a depression in the ground filled with sand. Traditionally, the custodianof this knowledgewas theWaterMan, represented in the paintingChildren’s Story (WaterDreaming forTwoChildren)by the Indigenous Australian artist Johnny Warangkula (19252001) as a figurewearing body paint and gesturingwith ritual devices. The skills and spatialmemoryof theWaterManwere indispensable. He knew how to scoop sand from a soak until water seeped into the base of the hole and how to find water
Indium-111-monoclonal antimyosin antibody studies after the first year of heart transplantation. Identification of risk groups for developing rejection during long-term follow-up and clinical implications.
Authors: M Ballester, D Obrador, I Carrió, J M Augé, C Moya, G Pons-Lladó, J M Caralps-Riera
Journal: Circulation (1990)

The long-term clinical course and results of biopsies in 21 patients studied with monoclonal antimyosin antibodies more than 12 months after heart transplantation according to the presence and degree of antimyosin-antibody uptake is described. Eighteen men and three women aged 20-52 years (39 +/- 9 years) were studied with antimyosin antibodies 12-40 months (mean, 22 +/- 9 months) after heart transplantation, and followed for a mean of 18 months (10-28 months). The number of biopsies performed during follow-up was 102. Results showed normal antimyosin-antibody studies in nine patients and abnormal studies in 12 patients. Myocyte damage was identified in 18 of the 102 biopsies (17.6%), one in the normal antimyosin-antibody group of patients and 17 in those patients with myocardial antimyosin-antibody uptake. Patients who developed rejection comprised 11% and 67% of each respective group; the mean number of rejection episodes per patient was 0.11 +/- 0.33 and 1.41 +/- 1.41, respectively (p less than 0.01). A trend was noted by which higher heart-to-lung ratios were associated with greater probability of rejection. Conclusively, 1) antimyosin-antibody studies performed after more than 1 year after heart transplantation indicate the presence and level of rejection activity, 2) groups of patients at risk for developing rejection at biopsy during long-term follow-up may be detected by antimyosin-antibody study, and 3) surveillance for rejection and the degree of immunosuppression should be tailored to meet individual patient needs.
To Smoke, to Live, to Die
Authors: Hugh H. Hussey
Journal: JAMA (1974)

"Hollywood Squares," of Monday and Friday evenings in Chicago, is a favored family show, judging by its ratings. Although most of the questions directed to the panel of stars by the urbane Master Peter Marshall are clean, an occasional response, by innuendo, smudges the preliminary remark a bit—never objectionably, or it's blanked out. Yet, a "clean" question directed to Redd Foxx (or is it Fox?) raised some hackles. The question went something like this: "Are more persons who live a hundred years or longer smokers or nonsmokers?" Redd, perhaps better known as Fred Sanford of "Sanford and Son," cigarette moving from hand to mouth, answered, "Yes, smokers live longer." Whether the contestant in the game agreed or not is beside the point. Peter Marshall announced that more centenarians are smokers. He did not give a source for his pronouncement, nor did he say anything about smokers of what—cigarettes, cigars, pipe—tobacco, corn
Left Ventricular Function and Coronary Artery Anatomy Before and After Myocardial Infarction
Authors: DOUGLAS K. STEWART, GLEN W. HAMILTON, JOHN A. MURRAY, J. WARD KENNEDY
Journal: Circulation (1974)

Six patients underwent cardiac catheterization before and after occurrence of a myocardial infarction. Results from the two procedures allowed the quantitation of changes in coronary artery anatomy and left ventricular performance associated with myocardial infarction. Left ventricular biplane or single plane angiography and selective coronary angiography were used to evaluate coronary artery anatomy, left ventricular end diastolic pressure (LVEDP), left ventricular end diastolic volume (LVEDV), end systolic volume (LVESV), and systolic ejection fraction (SEF) under resting conditions. Four patients had developed occlusion of the artery supplying the area of infarction. In five cases new or progressive contraction abnormalities occurred. One patient had no change in contraction pattern or SEF. Systolic ejection fraction fell in three patients, with no change in LVEDV. In two patients LVEDV rose and SEF fell. These data demonstrate that a wide spectrum of functional abnormalities is associated with myocardial infarction. Infarction was always associated with significant coronary artery stenosis, but not necessarily associated with occlusion. The SEF and contractile pattern were the indicators of left ventricular dysfunction which most frequently deteriorated.
Chronically sick penalised in the Netherlands
Authors: T Sheldon
Journal: BMJ (1994)

Thousands of chronically sick and disabled people in the Netherlands now face bills of pounds sterling 1000 or more for care previously covered by national insurance schemes, according to the Dutch national committee for chronically sick people. Under changes in the law brought in on 1 January and 1 April, patients requiring expensive diets, such as those suffering from coeliac disease, will no longer receive financial help to meet costs believed to amount to pounds sterling 1000 a year. Patients needing medical instruments such as hearing aids, and orthopaedic shoes will have to meet 15% of the …
NHS reforms will distract GPs from the work that "really matters"
Authors: N. Hawkes
Journal: BMJ (2011)

NHS reorganisation in England will distract GPs from what they do best, a seminar in London was told by Clare Gerada, chairwoman of the Royal College of General Practitioners. She found support for her view from the shadow health secretary, John Healey, but was challenged by another GP, Johnny Marshall.

The Westminster Health Forum seminar held at the Royal College of Surgeons examined how putting commissioning into GPs’ hands would change their role. Dr Gerada, herself the daughter of a singlehanded GP, said that the pattern of general practice was recognisably the same today as it had been 50 years ago. GPs were pragmatists and were working tremendously hard to make the reforms work, she said, but what really mattered was their relations with their patients, improving patients’ access …
Subclavian-Mammary Vein Catheterization
Authors: Michael T. Finch
Journal: JAMA (1976)

<h3>To the Editor.—</h3> My colleagues and I were interested to see the paper by Oakes and Wilson (233:532, 1975) about internal mammary vein catheterization because we have done the same. However, because of the patient's right-sided chest pain, it took us less than a day to discover our error. <h3>Report of a Case.—</h3> An 18-year-old woman with a complicated problem had a routine hyperalimentation catheter change. A subsequent posteroanterior x-ray film (Fig 1) seemed to show normal placement. Soon after we started the infusion, the patient complained of a vague right-sided chest pain. This became severe with an injection of cephalothin sodium (Keflin) in the same catheter. We should comment that this occurred in 1970 and we no longer use a hyperalimentation line for any other purpose. Because of her discomfort we took her to the x-ray department and injected diatrizoate meglumine 52% and diatrizoate sodium 8% (Renografin-60) (Fig 2).
The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease
Authors: Mark M.W. Chong, Jeffrey P. Rasmussen, Alexander Y. Rudensky, Dan R. Littman
Journal: The Journal of Experimental Medicine (2008)

MicroRNAs (miRNAs) are implicated in the differentiation and function of many cell types. We provide genetic and in vivo evidence that the two RNaseIII enzymes, Drosha and Dicer, do indeed function in the same pathway. These have previously been shown to mediate the stepwise maturation of miRNAs (Lee, Y., C. Ahn, J. Han, H. Choi, J. Kim, J. Yim, J. Lee, P. Provost, O. Radmark, S. Kim, and V.N. Kim. 2003. Nature. 425:415–419), and genetic ablation of either within the T cell compartment, or specifically within Foxp3+ regulatory T (T reg) cells, results in identical phenotypes. We found that miRNA biogenesis is indispensable for the function of T reg cells. Specific deletion of either Drosha or Dicer phenocopies mice lacking a functional Foxp3 gene or Foxp3+ cells, whereas deletion throughout the T cell compartment also results in spontaneous inflammatory disease, but later in life. Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity.
Modeling the Spread of HIV
Authors: Stanley L. Dolins
Journal: JAMA (1989)

<h3>To the Editor.—</h3> The data concerning the explosive spread of human immunodeficiency virus in intravenous drug abusers in New York City (1978 through 1984) and then its marked leveling off, as presented by Des Jarlais et al,<sup>1</sup>cannot be predicted by simple diffusion models of infection. We agree with these findings as far as they go; however, we have found that observed behavior follows directly from the nature of the disease. Consider a risk model consisting of two interacting cohorts of intravenous drug abusers where the disease first appears and spreads in the high-risk group, subsequently penetrating and then spreading more slowly in the lower-risk group. Carriers are eliminated by developing clinical acquired immunodeficiency syndrome. The incubation period is modeled as a sequence of four exponentially distributed states, with mean times of 6 weeks, 2 years, 11 years, and 1.5 years, yielding a median incubation of 10 years and
Genetic Risk Factors for Lumbar Disk Disease
Authors: Joan C. Marini
Journal: JAMA (2001)

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
CLCN5 mutation Ser244Leu is associated with X-linked renal failure without X-linked recessive hypophosphatemic rickets
Authors: Catherine L. Kelleher, Vardaman M. Buckalew, Edward D. Frederickson, Donna J. Rhodes, David A. Conner, Jonathan G. Seidman, Christine E. Seidman
Journal: Kidney International (1998)