tbuckley/cabot-search huggingface dataset:
Age, Sex, and<i>APOE</i>ε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span
Authors: Clifford R. Jack, Heather J. Wiste, Stephen D. Weigand, David S. Knopman, Prashanthi Vemuri, Michelle M. Mielke, Val Lowe, Matthew L. Senjem, Jeffrey L. Gunter, Mary M. Machulda, Brian E. Gregg, V. Shane Pankratz, Walter A. Rocca, Ronald C. Petersen
Journal: JAMA Neurology (2015)

Typical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.To compare age, sex, and APOE ε4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.Cross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.Memory, HVa, and amyloid PET.Overall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P < .001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P < .001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ε4 status at any age. From age 70 years onward, APOE ε4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ε4 carriers and 64 years for noncarriers.Male sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ε4 is not. In contrast, APOE ε4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than β-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which β-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with β-amyloid deposits.
Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial
Authors: Christophe Le Tourneau, Jean-Pierre Delord, Anthony Gonçalves, Céline Gavoille, Coraline Dubot, Nicolas Isambert, Mario Campone, Olivier Trédan, Marie-Ange Massiani, Cécile Mauborgne, Sebastien Armanet, Nicolas Servant, Ivan Bièche, Virginie Bernard, David Gentien, Pascal Jezequel, Valéry Attignon, Sandrine Boyault, Anne Vincent-Salomon, Vincent Servois, Marie-Paule Sablin, Maud Kamal, Xavier Paoletti
Journal: The Lancet Oncology (2015)
Initial Combination Therapy With Alogliptin and Pioglitazone in Drug-Naïve Patients With Type 2 Diabetes
Authors: Julio Rosenstock, Silvio E. Inzucchi, Jochen Seufert, Penny R. Fleck, Craig A. Wilson, Qais Mekki
Journal: Diabetes Care (2010)

OBJECTIVE To assess the efficacy and tolerability of alogliptin plus pioglitazone for initial combination therapy in drug-naïve type 2 diabetic patients. RESEARCH DESIGN AND METHODS This 26-week, double-blind, parallel-group study randomized 655 patients with inadequately controlled type 2 diabetes to four arms: 25 mg alogliptin (A25) q.d. monotherapy, 30 mg pioglitazone (P30) q.d. monotherapy, or 12.5 (A12.5) or 25 mg alogliptin q.d. plus pioglitazone (P30) q.d. combination therapy. Primary efficacy was A1C change from baseline with the high-dose combination (A25 + P30) versus each monotherapy. RESULTS Combination therapy with A25 + P30 resulted in greater reductions in A1C (−1.7 ± 0.1% from an 8.8% mean baseline) vs. A25 (−1.0 ± 0.1%, P &amp;lt; 0.001) or P30 (−1.2 ± 0.1%, P &amp;lt; 0.001) and in fasting plasma glucose (−2.8 ± 0.2 mmol/l) vs. A25 (−1.4 ± 0.2 mmol/l, P &amp;lt; 0.001) or P30 (−2.1 ± 0.2 mmol/l, P = 0.006). The A25 + P30 safety profile was consistent with those of its component monotherapies. CONCLUSIONS Alogliptin plus pioglitazone combination treatment appears to be an efficacious initial therapeutic option for type 2 diabetes.
A case of advanced cutaneous squamous cell carcinoma of the lower eyelid that was successfully treated with tegafur-gimeracil-oteracil potassium monotherapy
Authors: Yuriko Yamamoto, Noriaki Nakai, Yusuke Wakabayashi, Yasutaro Okuzawa, Jun Asai, Hideya Takenaka, Norito Katoh
Journal: Journal of the American Academy of Dermatology (2012)
Response to Letter Regarding Article, “Surgery in Adults With Congenital Heart Disease”
Authors: A.C. Zomer, C.L. Verheugt, T.C. Konings, I. Vaartjes, C.S.P.M. Uiterwaal, D.E. Grobbee, M.M. Langemeijer, D.R. Koolbergen, M.G. Hazekamp, J.P. van Melle, L. Bellersen, B.J.M. Mulder
Journal: Circulation (2012)

We thank Drs Le-Xin Wang and Zeng-Shan Ma for their comments on our publication. 1The authors state that pre-and postoperative pulmonary arterial pressure and ventricular function are important factors influencing long-term survival after corrective surgery. 2,3Therefore, they contend that without considering these factors in the analyses of long-term survival after surgery, the sex differences we reported require cautious interpretation.We recognize that pulmonary arterial pressure and ventricular function are important factors influencing long-term outcome after surgery. 2,3However, we did not have access to clinical information, and therefore we could not include these factors in our analyses.Nevertheless, we question whether these factors might explain the worse long-term survival of men after surgery in adulthood.To date, there is little indication that pulmonary arterial hypertension or ventricular dysfunction are more prevalent in men with congenital heart disease than in women. 4 -6Therefore, we do not expect that accounting for pulmonary pressure and ventricular function would significantly influence our results regarding sex differences in long-term survival after surgery.However, additional research on sex differences in adult congenital heart disease is necessary to provide more answers.Furthermore, our colleagues state that, in their experience, corrective surgery in adults with congenital heart disease can be considered curative in most cases, because in their center the vast majority enjoy a good outcome with little or no need for reoperations. 3Although we agree that for many patients corrective surgery might be considered curative, our results show this is not necessarily true for all.Furthermore, it is important to consider the follow-up period when discussing the need for reoperations.It might be that the need for reoperations can only be shown during a longer follow-up.
Pharmacotherapy for Adolescent Obesity
Authors: Alain Joffe
Journal: JAMA (2005)

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
Clinical Benefit of Lapatinib-Based Therapy in Patients with Human Epidermal Growth Factor Receptor 2–Positive Breast Tumors Coexpressing the Truncated p95HER2 Receptor
Authors: Maurizio Scaltriti, Sarat Chandarlapaty, Ludmila Prudkin, Claudia Aura, José Jimenez, Pier Davide Angelini, Gertrudis Sánchez, Marta Guzman, Josep Lluis Parra, Catherine Ellis, Robert Gagnon, Maria Koehler, Henry Gomez, Charles Geyer, David Cameron, Joaquin Arribas, Neal Rosen, José Baselga
Journal: Clinical Cancer Research (2010)

A subgroup of human epidermal growth factor receptor 2 (HER2)-overexpressing breast tumors coexpresses p95HER2, a truncated HER2 receptor that retains a highly functional HER2 kinase domain but lacks the extracellular domain and results in intrinsic trastuzumab resistance. We hypothesized that lapatinib, a HER2 tyrosine kinase inhibitor, would be active in these tumors. We have studied the correlation between p95HER2 expression and response to lapatinib, both in preclinical models and in the clinical setting.Two different p95HER2 animal models were used for preclinical studies. Expression of p95HER2 was analyzed in HER2-overexpressing breast primary tumors from a first-line lapatinib monotherapy study (EGF20009) and a second-line lapatinib in combination with capecitabine study (EGF100151). p95HER2 expression was correlated with overall response rate (complete + partial response), clinical benefit rate (complete response + partial response + stable disease > or =24 wk), and progression-free survival using logistic regression and Cox proportional hazard models.Lapatinib inhibited tumor growth and the HER2 downstream signaling of p95HER2-expressing tumors. A total of 68 and 156 tumors from studies EGF20009 and EGF100151 were evaluable, respectively, for p95HER2 detection. The percentage of p95HER2-positive patients was 20.5% in the EGF20009 study and 28.5% in the EGF100151 study. In both studies, there was no statistically significant difference in progression-free survival, clinical benefit rate, and overall response rate between p95HER2-positive and p95HER2-negative tumors.Lapatinib as a monotherapy or in combination with capecitabine seems to be equally effective in patients with p95HER2-positive and p95HER2-negative HER2-positive breast tumors.
Profilins constitute a novel family of functional plant pan-allergens.
Authors: R Valenta, M Duchene, C Ebner, P Valent, C Sillaber, P Deviller, F Ferreira, M Tejkl, H Edelmann, D Kraft
Journal: The Journal of Experimental Medicine (1992)

Type I allergy is a major health problem in industrialized countries where up to 15% of the population suffer from allergic symptoms (rhinitis, conjunctivitis, and asthma). Previously, we identified a cDNA clone that encoded a birch pollen allergen as profilin. Profilins constitute a ubiquitous family of proteins that control actin polymerization in eukaryotic cells; in particular, profilin participates in the acrosomal reaction of animal sperm cells. Although profilins had been unknown in plants so far, our finding led to the assumption that profilins might have similar functions in pollens during plant fertilization and therefore represent allergenic components in almost all pollens. We show that profilins are prominent allergens that can be isolated from tree pollens (Betula verrucosa, birch), from pollens of grasses (Phleum pratense, timothy grass), and weeds (Artemisia vulgaris, mugwort). About 20% of all pollen allergic patients tested (n = 65) displayed immunoglobulin E (IgE) reactivity to recombinant birch profilin that was expressed in pKK223-3. An IgE inhibition experiment performed with recombinant birch profilin and purified natural profilins from timothy grass and mugwort indicates common IgE epitopes. Moreover, all pollen profilins purified from these far distantly related plant species, and likewise the purified recombinant birch profilin, are able to elicit dose-dependent histamine release via high affinity Fc epsilon receptor of blood basophils from profilin allergic patients. The presence of profilin and possibly related proteins as crossreacting allergenic components in various plants therefore provides an explanation as to why certain allergic patients display type I allergic reactions with pollens and even food from distantly related plants. A functional pan-allergen, like profilin, available as purified recombinant protein, may be a useful diagnostic and probably therapeutic reagent.
Reduction of Human Metastatic Breast Cancer Cell Aggressiveness on Introduction of Either Form A or B of the Progesterone Receptor and Then Treatment with Progestins
Authors: Tomoki Sumida, Yoko Itahana, Hiroyuki Hamakawa, Pierre-Yves Desprez
Journal: Cancer Research (2004)

Abstract The sex steroid hormone progesterone (Pg) is critically involved in the development of the mammary gland, and it also is thought to play a role in breast cancer progression. However, the effect of Pg on malignant phenotypes is not fully understood in breast cancer. We previously reported that in Pg receptor (PR)–positive T47D breast cancer cells, Pg was able to counterbalance the stimulatory effect of estrogen or serum on proliferation and on expression level of Id-1, which generally stimulates cell proliferation and inhibits differentiation. Conversely, metastatic MDA-MB231 breast cancer cells lack PR and express high levels of Id-1 constitutively, and Pg showed no effect on Id expression, proliferation, and invasion in these cells. However, after introducing PR (either PR-A or PR-B) into MDA-MB231 cells, Pg inhibited the expression of Id-1 mRNA drastically. PR-transfected MDA-MB231 cells exhibited less proliferative activity after Pg treatment than parental or control MDA-MB231 cells, an effect which correlated well with reduction of Id-1 mRNA. This inhibitory effect on proliferation was accompanied by p21 up-regulation and c-myc down-regulation. Moreover, Pg-treated PR transfectants showed significant morphologic change, appearing more flattened and spread out than control ethanol-treated cells. Boyden chamber invasion assay revealed that PR-transfected MDA-MB231 cells also lost most of their invasive properties after Pg treatment. Zymographic analysis revealed that Pg drastically inhibited matrix metalloproteinase-9 (MMP-9) activity in cells transfected with either PR-A or PR-B. To determine whether Id-1 could act as a key mediator of the effects of Pg, we prepared cells transfected with Id-1 and PR. The morphologic change and p21 up-regulation still were observed after Pg treatment. However, c-myc down-regulation was not observed; the proliferative and invasive activities were mostly recovered; and MMP-9 down-regulation could not be detected anymore. From these observations, we conclude that either form of the PR is sufficient to reduce the malignant phenotypes on treatment with Pg and that Id-1 plays an important role as a mediator of the effects of Pg on breast cancer cell proliferation and invasion.
Synonymous Codon Bias Is Not Caused by Mutation Bias in G+C-Rich Genes in Humans
Authors: Nick G. C. Smith, Adam Eyre-Walker
Journal: Molecular Biology and Evolution (2001)

It is has been suggested that synonymous codon bias is a consequence of mutation bias in mammals. We tested this hypothesis in humans using single-nucleotide polymorphism data. We found a pattern of polymorphism which was inconsistent with the mutation bias hypothesis in G+C-rich genes. However, the data were consistent with the action of natural selection or biased gene conversion. Similar patterns of polymorphism were also observed in noncoding DNA, suggesting that natural selection or biased gene conversion may affect large tracts of the human genome.
Are We Training Too Many Subspecialists?
Authors: Leonard Sax
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Schwartz et al<sup>1</sup>ask: Are we training too many medical subspecialists? Most of their article is devoted to demonstrating that many small cities and towns do not have their own hematologist, endocrinologist, or pulmonologist. The authors draw a startling conclusion from this unremarkable finding: they believe that there is, and will continue to be, a significant shortage of medical subspecialists. This conclusion makes sense only if you believe, as they do, that every small town<i>needs</i>every kind of medical subspecialist: "We believe that cities with a population over 50 000 easily warrant the presence of at least one board-certified subspecialist in each field (including rheumatology, nephrology, endocrinology, and so on)." They give two grounds for this questionable belief. First, "cities with a population of 50 000 to 125 000 have an average of... 343 occupied beds" and, second, "subspecialists in these cities will also treat
Fatal Ectopic Pregnancy After Attempted Legally Induced Abortion
Authors: George L. Rubin
Journal: JAMA (1980)

From 1973 through 1978, the Center for Disease Control identified ten deaths caused by ruptured ectopic pregnancy after attempted legal abortions for those pregnancies. The women ranged in age from 18 to 31 years, seven were black, three were white, and five were nulliparous. The estimated gestational age was 16 menstrual weeks or earlier. In seven cases tissue obtained at abortion was sent for outside microscopic pathological examination; attempts to contact four of the patients when no products of conception were found were unsuccessful. An important factor in preventing fatal ectopic pregnancy for women who have legal abortions is the identification of products of conception at the time of the abortion procedure while the patient is still available for reexamination and recurettage. (<i>JAMA</i>244:1705-1708, 1980)
Number needed to treat in COPD: exacerbations versus pneumonias
Authors: Oliver N Keene, Antonio Anzueto, Gary T Ferguson, Peter M A Calverley
Journal: Thorax (2013)

Number needed to treat (NNT) is an attractive concept for clinicians, but its application to a treatment that reduces the frequency of COPD exacerbations is not straightforward. Dr Suissa1 proposes a method for calculating the NNT based on the Kaplan–Meier curve of time to first exacerbation. This approach ignores all exacerbations beyond the first one experienced by the patient and does not appropriately reflect the benefit of a treatment that reduces multiple exacerbations in the same patient.2 From a statistical viewpoint, the approach is not efficient as it does not use all the exacerbation data collected. Dr Suissa has himself previously advocated methods of analysis of exacerbations …
Right Ventricular Ischemic Injury in Patients With Acute ST-Segment Elevation Myocardial Infarction
Authors: Pier Giorgio Masci, Marco Francone, Walter Desmet, Javier Ganame, Giancarlo Todiere, Rocco Donato, Valeria Siciliano, Iacopo Carbone, Matteo Mangia, Elisabetta Strata, Carlo Catalano, Massimo Lombardi, Luciano Agati, Stefan Janssens, Jan Bogaert
Journal: Circulation (2010)

Experimental data show that the right ventricle (RV) is more resistant to ischemia than the left ventricle. To date, limited data are available in humans because of the difficulty of discriminating reversible from irreversible ischemic damage. We sought to characterize RV ischemic injury in patients with reperfused myocardial infarction using cardiovascular magnetic resonance.In 3 tertiary centers, 242 consecutive patients with reperfused acute ST-segment elevation myocardial infarction were studied with cardiovascular magnetic resonance at 1 week and 4 months after myocardial infarction. T2-weighted and postcontrast cardiovascular magnetic resonance scans were used to depict myocardial edema and late gadolinium enhancement, respectively. Early after infarction, RV edema was common (51% of patients), often associated with late gadolinium enhancement (31% of patients). Remarkably, RV edema and late gadolinium enhancement were found in 33% and 12% of anterior left ventricular infarcts, respectively. Baseline regional and global RV functions were inversely related to the presence and extent of RV edema and RV late gadolinium enhancement. At follow-up, a significant decrease in frequency (25/242 patients; 10%) and extent of RV late gadolinium enhancement was observed (P<0.001). With the use of multivariable analysis, the presence of RV edema was an independent predictor of RV global function improvement during follow-up (β-coefficient=0.221, P=0.003).Early postinfarction RV ischemic injury is common and is characterized by the presence of myocardial edema, late gadolinium enhancement, and functional abnormalities. RV injury is not limited to inferior infarcts but is commonly found in anterior infarcts as well. Cardiovascular magnetic resonance findings suggest reversibility of acute RV dysfunction with limited permanent myocardial damage at 4-month follow-up.
The Glomerular Epithelial Cell Anti-Adhesin Podocalyxin Associates with the Actin Cytoskeleton through Interactions with Ezrin
Authors: ROBERT A. ORLANDO, TETSURO TAKEDA, BEVERLY ZAK, SANDRA SCHMIEDER, VIVIAN M. BENOIT, TAMMIE MCQUISTAN, HEINZ FURTHMAYR, MARILYN G. FARQUHAR
Journal: Journal of the American Society of Nephrology (2001)

Abstract. During development, renal glomerular epithelial cells (podocytes) undergo extensive morphologic changes necessary for creation of the glomerular filtration apparatus. These changes include formation of interdigitating foot processes, replacement of tight junctions with slit diaphragms, and the concomitant opening of intercellular urinary spaces. It was postulated previously and confirmed recently that podocalyxin, a sialomucin, plays a major role in maintaining the urinary space open by virtue of the physicochemical properties of its highly negatively charged ectodomain. This study examined whether the highly conserved cytoplasmic tail of podocalyxin also contributes to the unique organization of podocytes by interacting with the cytoskeletal network found in their cell bodies and foot processes. By immunocytochemistry, it was shown that podocalyxin and the actin binding protein ezrin are co-expressed in podocytes and co-localize along the apical plasma membrane, where they form a co-immunoprecipitable complex. Selective detergent extraction followed by differential centrifugation revealed that some of the podocalyxin cosediments with actin filaments. Moreover, its sedimentation is dependent on polymerized actin and is mediated by complex formation with ezrin. Once formed, podocalyxin/ezrin complexes are very stable, because they are insensitive to actin depolymerization or inactivation of Rho kinase, which is known to be necessary for regulation of ezrin and to mediate Rho-dependent actin organization. These data indicate that in podocytes, podocalyxin is complexed with ezrin, which mediates its link to the actin cytoskeleton. Thus, in addition to its ectodomain, the cytoplasmic tail of podocalyxin also likely contributes to maintaining the unique podocyte morphology.
Pregnancy After Embryo Biopsy and Coamplification of DNA From X and Y Chromosomes
Authors: Jamie A. Grifo
Journal: JAMA (1992)

Reprint requests to Center for Reproductive Medicine and Infertility, Department of Obstetrics and Gynecology, Cornell University Medical College, 505 E 70th St, Room HT 300, New York, NY 10021 (Dr Grifo).