tbuckley/cabot-search huggingface dataset:
Health Status in Elderly Persons Living Alone—Reply
Authors: Carla Perissinotto, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Genome-forward oncology: how do we get there?
Authors: Matthew Ellis
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Preventive Strategies in Sexually Transmitted Diseases for the Primary Care Physician
Authors: Charles R. Horsburgh
Journal: JAMA (1987)

This study provides the background recommendations of the US Preventive Services Task Force for interventions by primary care physicians to prevent sexually transmitted diseases. Rationale for and data supporting use of barrier methods, epidemiologic treatment, contact tracing, patient education, prophylactic antibiotics, and disease reporting are discussed. Specific recommendations include those for gonorrhea, syphilis, human immunodeficiency virus infection, enteric infections, human papillomavirus infection, herpes simplex virus infection, and<i>Chlamydia trachomatis</i>infection. (<i>JAMA</i>1987;258:814-821)
A Preclinical Evaluation of Minnelide as a Therapeutic Agent Against Pancreatic Cancer
Authors: Rohit Chugh, Veena Sangwan, Satish P. Patil, Vikas Dudeja, Rajinder K. Dawra, Sulagna Banerjee, Robert J. Schumacher, Bruce R. Blazar, Gunda I. Georg, Selwyn M. Vickers, Ashok K. Saluja
Journal: Science Translational Medicine (2012)

Minnelide prevents tumor formation, causes tumor regression, and increases survival in multiple models of pancreatic cancer.
The Inhibitor of Apoptosis Protein Livin (ML-IAP) Plays a Dual Role in Tumorigenicity
Authors: Ihab Abd-Elrahman, Klilah Hershko, Tzahi Neuman, Boaz Nachmias, Riki Perlman, Dina Ben-Yehuda
Journal: Cancer Research (2009)

Abstract The inhibitor of apoptosis protein (IAP) family can inhibit apoptosis induced by a variety of stimuli. We and others previously described the IAP Livin (ML-IAP). We found that Livin is unique among the IAP members as, on a strong apoptotic stimulus, it is specifically cleaved by caspases to produce a truncated protein with paradoxical proapoptotic activity (tLivin). We also showed that Livin encodes two splicing variants, termed Livin α and β, with diverse antiapoptotic effects in vitro. In this study, we compared the Livin isoforms in vivo. An animal model was established and the effects of Livin α and β on the initiation and development of tumors were compared. In the animal model, Livin α promotes tumor initiation in comparison with control. Interestingly, the growth of tumors originating from cells expressing Livin β was inhibited. In these tumors, Livin β was cleaved and produced a high level of the proapoptotic tLivin β that repressed tumor development. When we eliminated the proapoptotic effect of Livin β by point mutations, the resulting antiapoptotic Livin β mutants contributed to tumor progression. In terms of mechanism, we show that Livin β tumors develop only in mice lacking natural killer (NK) cell activity. Thus, from the animal model, we can conclude that Livin plays a major role in tumorigenicity and that NK cells induce cleavage of Livin to its proapoptotic truncated protein that in turn inhibits tumor growth. Therefore, Livin and tLivin may serve as potential targets for cancer therapy. [Cancer Res 2009;69(13):5475–80]
Uric acid lowering therapy: prescribing patterns in a large cohort of older adults
Authors: D H Solomon, J Avorn, R Levin, M A Brookhart
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> Uric acid lowering therapy (UALT) is considered a chronic treatment for gout. Relatively little is known about adherence to UALT. <h3>Methods:</h3> We assessed adherence with UALT over a 1-year study period among 9823 older adults enrolled in a pharmacy benefit program. Two adherence measures were calculated, the percentage of days covered (PDC) and the time until an extended break (at least 60 days) in treatment. A PDC &lt;80% was considered poor adherence and its predictors were examined in multivariable logistic models. <h3>Results:</h3> The mean (SD) PDC was 54% (36%) with 64% of patients considered poorly compliant over the study period. A total of 56% had experienced an extended break in UALT. Predictors of poor adherence included younger age (odds ratio (OR) 1.50, 95% CI 1.33–1.69 for ages 65–74 compared with 85 and above) and African–American race (OR 1.86, 95% CI 1.52–2.27 compared with Caucasian race). Most patients (93%) received their initial UALT prescription from a non-specialist and this also predicted poor adherence (OR 1.15, 95% CI 0.96–1.38 compared with rheumatologists or nephrologists). <h3>Conclusion</h3> Adherence with UALT is poor. While uric acid levels were not measured in this study, poor adherence with UALT is likely to reduce attainment of goal uric acid levels.
CtBP2 Modulates the Androgen Receptor to Promote Prostate Cancer Progression
Authors: Ken-ichi Takayama, Takashi Suzuki, Tetsuya Fujimura, Tomohiko Urano, Satoru Takahashi, Yukio Homma, Satoshi Inoue
Journal: Cancer Research (2014)

The androgen receptor (AR) is the key driver of both early and advanced prostate cancer, making a complete understanding of its regulation important. Here, we report the identification of multiple AR-binding sites in the gene encoding the transcription factor CtBP2 (carboxyl terminal-binding protein), genetic variations of which have been associated with prostate cancer susceptibility. Notably, we found that SNPs in the human CTBP2 gene that were associated with prostate cancer development were correlated with AR-enhancer activity. High CtBP2 expression levels correlated with poor prognosis in patients, whereas CtBP2 silencing reduced tumor growth in a mouse xenograft model of human prostate cancer. Consistent with its function as a transcriptional corepressor, CtBP2 repressed tumor-suppressor genes and AR corepressors in prostate cancer cells, such as NCOR and RIP140, by binding with AR to the promoter enhancers of these genes. Global gene-expression analyses revealed a positive effect on androgen-mediated gene expression, and CtBP2 silencing was found to increase AR interactions with corepressors that limit histone modification. Overall, our results show how CtBP2 contributes to prostate cancer progression by modulating AR and oncogenic signaling.
<b> <i>CYP3A4</i> </b>, <b> <i>CYP3A5</i> </b>, and <b> <i>CYP3A43</i> </b> Genotypes and Haplotypes in the Etiology and Severity of Prostate Cancer
Authors: Charnita Zeigler-Johnson, Tara Friebel, Amy H. Walker, Yiting Wang, Elaine Spangler, Saarene Panossian, Margerie Patacsil, Richard Aplenc, Alan J. Wein, S. Bruce Malkowicz, Timothy R. Rebbeck
Journal: Cancer Research (2004)

Abstract The CYP3A genes reside on chromosome 7q21 in a multigene cluster. The enzyme products of CYP3A4 and CYP3A43 are involved in testosterone metabolism. CYP3A4 and CYP3A5 have been associated previously with prostate cancer occurrence and severity. To comprehensively examine the effects of these genes on prostate cancer occurrence and severity, we studied 622 incident prostate cancer cases and 396 controls. Substantial and race-specific linkage disequilibrium was observed between CYP3A4 and CYP3A5 in both races but not between other pairs of loci. We found no association of CYP3A5 genotypes with prostate cancer or disease severity. CYP3A43*3 was associated with family history-positive prostate cancer (age- and race-adjusted odds ratio = 5.86, 95% confidence interval, 1.10–31.16). CYP3A4*1B was associated inversely with the probability of having prostate cancer in Caucasians (age-adjusted odds ratio = 0.54, 95% confidence interval, 0.32–0.94). We also observed significant interactions among these loci associated with prostate cancer occurrence and severity. There were statistically significant differences in haplotype frequencies involving these three genes in high-stage cases (P &amp;lt; 0.05) compared with controls. The observation that CYP3A4 and CYP3A43 were associated with prostate cancer, are not in linkage equilibrium, and are both involved in testosterone metabolism, suggest that both CYP3A4*1B and CYP3A43*3 may influence the probability of having prostate cancer and disease severity.
Adoptive Transfer of Tumor Reactive B Cells Confers Host T-Cell Immunity and Tumor Regression
Authors: Qiao Li, Xiangming Lao, Qin Pan, Ning Ning, Ji Yet, Yingxin Xu, Shengping Li, Alfred E. Chang
Journal: Clinical Cancer Research (2011)

We investigated the antitumor reactivity of adoptively transferred effector B cells and the mechanisms by which they may mediate tumor regression in a spontaneous metastases model.4T1 breast cancer cells were inoculated into the flanks of syngeneic Balb/C mice to prime draining lymph nodes. Tumor-draining lymph nodes (TDLN) were harvested and B cells activated ex vivo with lipopolysaccharide and anti-CD40 monoclonal antibody. These activated B cells were adoptively transferred into mice inoculated with 4T1 tumor in the mammary fat pad. The induction of host T-cell immunity was evaluated.Activated 4T1 TDLN B cells secreted immunoglobulin G (IgG) in response to tumor cells which was immunologically specific. These activated B cells were capable of mediating specific lysis of tumor cells in vitro. Transfer of these activated B cells alone mediated the inhibition of spontaneous metastases to the lung. Examination of the host revealed that the transfer of these B cells resulted in the induction of tumor-specific T-cell immunity as measured by cytotoxicity and cytokine (IFNγ and granulocyte-macrophage colony-stimulating factor) production. The combined transfer of activated T and B cells from TDLN resulted in tumor regression, which was greater than either cell population alone, with host B cells capable of producing IgG that mediated lysis of tumor in the presence of complement.We have found that appropriately primed B cells can mediate tumor regression by itself and confers host T-cell antitumor immunity. Furthermore, effector B cells can serve as a useful adjunct in adoptive T-cell therapy.
Evidence indicating independent assortment of framework and complementarity-determining segments of the variable regions of rabbit light chains. Delineation of a possible J minigene.
Authors: E A Kabat, T T Wu, H Bilofsky
Journal: The Journal of Experimental Medicine (1980)

Amino acid sequences of rabbit light chains show considerable evidence of independent assortment of framework (FR) and complementarity-determining (CDR) segments. This suggests that they are coded for by independent genetic units (minigaenes) and that individual light chains are assembled somatically by recombining these units. Identical FR sets with multiple members generally comprise chains with different specificities, whereas identical CDR sets tend to have chains of a single specificity. A J segment, which, by analogy with mouse light chains, is made up of the last two residues of CDR3 plus all of FR4, contained 18 different sets and could contribute to diversity generated by CDR3. The longest segment, FR3, had a very large number of sets. Evidence is presented showing that the number of sets could be substantially reduced by permitting FR3 to be formed by two independently assorting segments comprising residues 57-68 and 69-88.
Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity
Authors: Hang Fai Kwok, Richard J Buick, Diana Kuehn, Julie A Gormley, Declan Doherty, Thomas J Jaquin, Angela McClurg, Claire Ward, Teresa Byrne, Jacob Jaworski, Ka Lai Leung, Philip Snoddy, Christine McAnally, Roberta E Burden, Breena Gray, Jenny Lowry, Isabelle Sermadiras, Natalia Gruszka, Nigel Courtenay-Luck, Adrien Kissenpfennig, Christopher J Scott, James A Johnston, Shane A Olwill
Journal: Molecular Cancer (2011)

Proteolytic enzymes have been implicated in driving tumor progression by means of their cancer cell microenvironment activity where they promote proliferation, differentiation, apoptosis, migration, and invasion. Therapeutic strategies have focused on attenuating their activity using small molecule inhibitors, but the association of proteases with the cell surface during cancer progression opens up the possibility of targeting these using antibody dependent cellular cytotoxicity (ADCC). Cathepsin S is a lysosomal cysteine protease that promotes the growth and invasion of tumour and endothelial cells during cancer progression. Our analysis of colorectal cancer patient biopsies shows that cathepsin S associates with the cell membrane indicating a potential for ADCC targeting. Here we report the cell surface characterization of cathepsin S and the development of a humanized antibody (Fsn0503h) with immune effector function and a stable in vivo half-life of 274 hours. Cathepsin S is expressed on the surface of tumor cells representative of colorectal and pancreatic cancer (23%-79% positive expression). Furthermore the binding of Fsn0503h to surface associated cathepsin S results in natural killer (NK) cell targeted tumor killing. In a colorectal cancer model Fsn0503h elicits a 22% cytotoxic effect. This data highlights the potential to target cell surface associated enzymes, such as cathepsin S, as therapeutic targets using antibodies capable of elicitingADCC in tumor cells.
Serum autoantibodies in chronic hepatitis C: Comparison with autoimmune hepatitis and impact on the disease profile
Authors: F Cassani, M Cataleta, P Valentini, P Muratori, F Giostra, R Francesconi, L Muratori, M Lenzi, G Bianchi, D Zauli, F B Bianchi
Journal: Hepatology (1997)

Antibodies to nuclei (ANA), smooth muscle (SMA), and liver/kidney microsomes type 1 (anti-LKM1) may occur in chronic hepatitis C. Distinct subspecificities, including ANA with the homogeneous pattern (ANA-H) and SMA with antiactin specificity (SMA-AA), are found in autoimmune hepatitis (AIH). This study was performed to characterize the hepatitis C virus (HCV)-associated autoantibodies and to evaluate their influence on the profile of the disease. Two hundred ninety consecutive patients with chronic hepatitis C and 35 control cases with AIH were screened for autoantibodies by indirect immunofluorescence (IFL) at 1:40 serum dilution. The ANA pattern was defined by IFL on HEp-2 cells and the SMA-AA identified by the presence of at least two of the following elements: 1) SMA(T) or SMA(G) pattern by IFL on kidney sections; 2) XR 1 precipitating system by counterimmunoelectrophoresis; or 3) typical pattern by IFL on liver sections from phalloidin-intoxicated rats. ANA, SMA, and anti-LKM1 occurred in 9%, 20%, and 6% of chronic hepatitis C cases, respectively. The overall prevalence of autoantibodies was 30% (87 of 290). Compared with AIH, HCV-associated ANA and SMA exhibited ANA-H and SMA-AA at a lower prevalence (38% vs. 71%, P = .04 and 8% vs. 87%, P &lt; .000001, respectively) and had a lower median titer (1:80 vs. 1:320, P &lt; .001 and 1:40 vs. 1:320, P &lt; .000001, respectively). The concomitant positivity for ANA-H and SMA-AA was detected in none of the HCV cases, but in 46% of AIH sera ( P &lt; .000001). Two parameters were independently associated with the autoantibodies in chronic hepatitis C: high alanine transaminase (ALT) serum levels (F = 14.04) and female gender (F = 5.03). At the univariate analysis, patients with autoantibodies had a more severe portal-periportal necroinflammation (median Scheuer's score: 2.05 vs. 1.64, P = .003). The presence of autoantibodies did not influence the response to interferon (IFN). In chronic hepatitis C, serum autoantibodies are common, but their subspecificities are distinct from those occurring in AIH. Whereas the absence of ANA-H and/or SMA-AA does not exclude AIH, the characterization of ANA and SMA may help to discriminate between the two conditions. As compared with the seronegative counterpart, autoantibody-positive chronic hepatitis C is more common in females and exhibits a more severe biochemical and histological activity. The response to IFN therapy, however, is similar.
Suppression of airway hyperresponsiveness induced by ovalbumin sensitisation and RSV infection with Y-27632, a Rho kinase inhibitor
Authors: K Hashimoto
Journal: Thorax (2002)

<b>Background:</b> Smooth muscle contraction is one of the hallmarks of asthma. A recently developed pyridine derivative, Y-27632, a selective Rho kinase inhibitor, has been reported to inhibit the smooth muscle contraction of human and animal trachea in ex vivo systems but its effect in animal models of airway hyperresponsiveness (AHR) has not been examined. The purpose of this study was to evaluate the effect of Y-27632 in a murine model of allergic and virally induced AHR. <b>Methods:</b> Baseline lung resistance and methacholine induced AHR were measured in mice sensitised to ovalbumin (OVA) and also in mice infected with respiratory syncytial virus (RSV) following ovalbumin sensitisation (OVA/RSV). <b>Results:</b> Time course and dose ranging experiments indicated that 30 mg/kg Y-27632 given by gavage 2 hours before methacholine challenge significantly reduced baseline lung resistance and prevented AHR in OVA sensitised mice. Y-27632 also suppressed AHR induced by the bronchospastic agent serotonin in OVA sensitised mice and prevented methacholine induced AHR in OVA/RSV mice. <b>Conclusions:</b> These results suggest that the signalling pathway mediated through Rho kinase may have an important role in bronchial smooth muscle tone in allergen induced and virus induced AHR and should be considered as a novel target for asthma treatment.
Induction of HIV-1 Replication in Latently Infected CD4+ T Cells Using a Combination of Cytokines
Authors: Tae-Wook Chun, Delphine Engel, Stephanie B. Mizell, Linda A. Ehler, Anthony S. Fauci
Journal: The Journal of Experimental Medicine (1998)

Although it has been demonstrated that certain cytokines, particularly proinflammatory cytokines, can enhance ongoing viral replication in peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals, it is unclear what role these cytokines play in the induction of HIV-1 replication in latently infected, resting CD4(+) T cells. This study demonstrates that the in vitro combination of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha together with the immunoregulatory cytokine IL-2 are potent inducers of viral replication in highly purified, latently infected, resting CD4+ T cells derived from HIV-infected individuals who are antiretroviral therapy-naive as well as those who are receiving highly active antiretroviral therapy (HAART). Viral replication induced by this combination of cytokines was completely suppressed in the presence of HAART in vitro. Given that an array of cytokines, including IL-6, TNF-alpha, and IL-2, are copiously expressed in the microenvironment of the lymphoid tissues, which harbor the latent viral reservoirs, induction of HIV by this combination of cytokines may in part explain the commonly observed reappearance of detectable plasma viremia in HIV-infected individuals in whom HAART was discontinued. Moreover, since it is likely that these infected cells die upon activation of virus and that HAART prevents spread of virus to adjacent cells, the observation that this combination of cytokines can markedly induce viral replication in this reservoir may have important implications for the activation-mediated diminution of the latent reservoir of HIV in patients receiving HAART.
Vitiligo as a Sequela of Influenza and Erysipelas
Authors: E. M. Sympson
Journal: BMJ (1891)

nuclei amongst which they lie.The various methods used for staining the sections were Neelson's fluid, picrocarmine, safranine, and logwood.Sections stained with Neelson's fluid showed tlle coccidia perhaps the best.In the scrapings treated with liquor potassae, quite a small number were found in comparison with the case reported by Mr. Jonathan Hlutchinson, jun., F.R.C.S., in the Pathological Society's Tran- sactions for 1890.PsonosPE}niosIs.-In 1]889 Darier demonstrated ac monlocellular parasite belonging to tlhe class sporozoa-Order, psoros- permia-as beinig always present in the skin and gland ducts in cases of Paget's disease of the nipple and acn6 corn&e.Dr. Louis Wicklham's monograplh on this subject4 is well known.The parasites were seen by these observers in various stages of their growtlh.At the first they consisted of amce- boid masses like cellular protoplasm.The cell containing
Changes to inhaled corticosteroid dose when initiating combination inhaler therapy in long-acting β agonist-naïve patients with asthma: a retrospective database analysis
Authors: Jordan R Covvey, Blair F Johnston, Fraser Wood, Anne C Boyter
Journal: Thorax (2014)

Retrospective prescribing data were obtained from 46 general practice surgeries in NHS Scotland. Patients with asthma who were naïve to previous long-acting β agonist therapy and initiated combination inhaler therapy in 2008–2009 were classified according to the inhaled corticosteroid (ICS) dose in their combination inhaler compared with the highest dose of ICS they received before initiation. Among the 685 patients (541 (79.0%) who had been prescribed an ICS previously), those originally on low-, medium- or high-dose ICS were changed to high-dose combination therapy in 122/250 (48.8%), 94/151 (62.3%) or 85/113 (75.2%) cases in each ICS dose category, respectively. These results suggest that evaluation of appropriate high-dose ICS prescribing in general practice is needed.