tbuckley/cabot-search huggingface dataset:
Mapping of a quantitative trait locus for blood pressure on rat chromosome 2.
Authors: A Y Deng, H Dene, J P Rapp
Journal: Journal of Clinical Investigation (1994)

A genetic map for rat chromosome 2 that includes five candidate genes for blood pressure regulation was constructed in a region containing a quantitative trait locus (QTL) for blood pressure. Two F2 populations of male rats raised on high salt (8% NaCI) diet from weaning were studied: F2(WKY x S), derived from a cross of Dahl salt-sensitive rats (S) and Wistar-Kyoto rats (WKY); and F2(MNS x S), derived from a cross of S rats and Milan normotensive strain (MNS). In both populations a blood pressure QTL was localized between Na+,K(+)-ATPase alpha 1 isoform and calmodulin-dependent protein kinase II-delta loci. The LOD score for existence of this blood pressure QTL based on the combined populations (n = 330) was 5.66 and accounted for 9.2% of the total variance and 26% of the genetic variance.
Clinical Trial Data as a Public Good
Authors: Marc A. Rodwin, John D. Abramson
Journal: JAMA (2012)

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
INHERITED AND ACQUIRED FACTORS IN RESISTANCE TO INFECTION
Authors: Leslie T. Webster
Journal: The Journal of Experimental Medicine (1933)

1. Mice with relatively great inherent resistance to certain bacterial infections were heavier but not more fertile than mice with relatively little inherent resistance. Mice with relatively little inherent resistance were with one exception not abnormally low in weight. 2. B. enteritidis given intrastomachally to susceptibles appeared in the blood stream more promptly, in larger numbers, and in a greater percentage of cases, and was present in feces in larger numbers, for a longer period, and in a greater percentage of cases than when given to resistants. 3. Mice relatively resistant to B. enteritidis administered by the natural gastrointestinal route were likewise resistant to the organisms introduced subcutaneously, intraperitoneally, and intravenously. Mice relatively susceptible to the organisms administered by the natural route were susceptible when the organisms were injected directly into tissues and blood stream. 4. Of four lines of mice relatively susceptible to B. enteritidis, three were likewise susceptible to Pasteurella avicida, B. friedlaenderi, and pneumococcus given intranasally. A fourth line was significantly more resistant. Lines of mice relatively resistant to B. enteritidis were likewise resistant to the three respiratory tract pathogens. 5. When Pasteurella avicida, B. friedlaenderi, and pneumococcus were injected intraperitoneally or intravenously, no significant differences in duration of life of the several lines of mice could be demonstrated. 6. Of four lines relatively susceptible to B. enteritidis, two were susceptible to an intranasal instillation of louping ill virus. Lines resistant to B. enteritidis proved relatively susceptible to the virus infection.
Phase I study of the effects of renal impairment on the pharmacokinetics and safety of satraplatin in patients with refractory solid tumors
Authors: M.D. Galsky, L.H. Camacho, E.G. Chiorean, D. Mulkerin, D.S. Hong, W.K. Oh, D.F. Bajorin
Journal: Annals of Oncology (2011)
Randomized Trial of Atorvastatin for Reduction of Myocardial Damage During Coronary Intervention
Authors: Vincenzo Pasceri, Giuseppe Patti, Annunziata Nusca, Christian Pristipino, Giuseppe Richichi, Germano Di Sciascio
Journal: Circulation (2004)

Small myocardial infarctions after percutaneous coronary intervention have been associated with higher risk of cardiac events during follow-up. Observational studies have suggested that statins may lower the risk of procedural myocardial injury. The aim of our study was to confirm this hypothesis in a randomized study.One hundred fifty-three patients with chronic stable angina without previous statin treatment were enrolled in the study. Patients scheduled for elective coronary intervention were randomized to atorvastatin (40 mg/d, n=76) or placebo (n=77) 7 days before the procedure. Creatine kinase-MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after the procedure. Detection of markers of myocardial injury above the upper normal limit was significantly lower in the statin group versus the placebo group: 12% versus 35% for creatine kinase-MB (P=0.001), 20% versus 48% for troponin I (P=0.0004), and 22% versus 51% for myoglobin (P=0.0005). Myocardial infarction by creatine kinase-MB determination was detected after coronary intervention in 5% of patients in the statin group and in 18% of those in the placebo group (P=0.025). Postprocedural peak levels of creatine kinase-MB (2.9+/-3 versus 7.5+/-18 ng/mL, P=0.007), troponin I (0.09+/-0.2 versus 0.47+/-1.3 ng/mL, P=0.0008), and myoglobin (58+/-36 versus 81+/-49 ng/mL, P=0.0002) were also significantly lower in the statin than in the placebo group.Pretreatment with atorvastatin 40 mg/d for 7 days significantly reduces procedural myocardial injury in elective coronary intervention. These results may influence practice patterns with regard to adjuvant pharmacological therapy before percutaneous revascularization.
Left ventricular function depends on previous beat ejection but not previous beat pressure load.
Authors: B K Slinker, S G Shroff, R D Kirkpatrick, K B Campbell
Journal: Circulation Research (1991)

Previous beat contraction history, in which the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, may be important in the beat-to-beat regulation of left ventricular performance in the intact cardiovascular system. Prior studies of this phenomenon have established that mechanical events of the previous beat influence the function of the current beat, but it is not known whether the important mechanical influence is exerted by previous beat ejection or previous beat pressure. In addition, the magnitude of the effect of previous beat contraction history on left ventricular performance is unknown. To make these determinations, we performed experiments in six isolated rabbit left ventricle preparations buffer perfused at 30 degrees C. Left ventricular pressure and volume were controlled precisely with a servo-controlled linear motor system. After steady-state ejecting conditions were established by clamping left ventricular ejection pressure at 60% of peak isovolumic pressure, single test beats, which were pressure clamped at 40%, 60%, 80%, and 100% of peak isovolumic pressure, were introduced and followed by an isovolumic reference beat. As the level of pressure clamp decreased from 100% to 40%, developed pressure on the isovolumic beat following the single test beats increased from 139 +/- 15 (mean +/- SD) to 151 +/- 13 mm Hg. Similarly, peak positive left ventricular dP/dt increased from 1,718 +/- 209 to 1,864 +/- 181 mm Hg.sec-1 (both p less than 0.01). Multiple regression analysis showed that this increase in left ventricular function was related to previous beat ejection but not to previous beat pressure load or relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression and function of EZH2 in synovial fibroblasts: epigenetic repression of the Wnt inhibitor SFRP1 in rheumatoid arthritis
Authors: M. Trenkmann, M. Brock, R. E. Gay, C. Kolling, R. Speich, B. A. Michel, S. Gay, L. C. Huber
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To study the expression, regulation and function of the histone methyltransferase enhancer of zeste homologue 2 (EZH2) in synovial fibroblasts (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). <h3>Methods</h3> SF were obtained from RA and OA patients undergoing joint surgery. Expression levels were assessed by quantitative real-time PCR and western blot. Kinase inhibitors and reporter gene assays were employed to study signalling pathways. Functional analyses included EZH2 overexpression by plasmid transfection and gene silencing by small interfering RNA. Chromatin immunoprecipitation assay was used to analyse histone methylation within distinct promoter regions. <h3>Results</h3> By studying the expression and function of EZH2 in SF the authors found that EZH2 is overexpressed in rheumatoid arthritis synovial fibroblasts (RASF) and further induced by tumour necrosis factor alpha through the nuclear factor kappa B and Jun kinase pathways. As a target gene of EZH2 the authors identified secreted frizzled-related protein 1 (SFRP1), an inhibitor of Wnt signalling, which is associated with the activation of RASF, and show that SFRP1 expression correlates with the occupation of its promoter with activating and silencing histone marks. <h3>Conclusions</h3> These data strongly suggest that the chronic inflammatory environment of the RA joint induces EZH2 and thus might cause changes in the epigenetic programmes of SF.
Multicentre intraindividual randomized trial of topical methyl aminolaevulinate–photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities
Authors: R. Kaufmann, L. Spelman, W. Weightman, J. Reifenberger, R.-M. Szeimies, E. Verhaeghe, N. Kerrouche, V. Sorba, H. Villemagne, L.E. Rhodes
Journal: British Journal of Dermatology (2008)

Methyl aminolaevulinate-photodynamic therapy (MAL-PDT) is an effective treatment in facial/scalp actinic keratosis (AK).The aims of this study were to compare efficacy, safety, cosmetic outcome and patient preference of MAL-PDT vs. cryotherapy in patients with AK at other locations.A multicentre, controlled, randomized, open, intraindividual, right-left comparison was performed. Patients with nonhyperkeratotic AK were treated once with MAL-PDT and cryotherapy on either side of the body. At week 12, lesions showing noncomplete response were retreated. The primary efficacy variable was the lesion response at week 24. Investigator's assessment of cosmetic outcome, patient's preference in terms of cosmetic outcome and a patient preference questionnaire were also analysed at week 24.In total, of 121 patients with 1343 lesions (98% located on the extremities and the remainder on the trunk and neck) were included. Both treatments provided a high mean percentage reduction in lesion count at week 24 with significantly higher efficacy for cryotherapy: 78% for MAL-PDT and 88% for cryotherapy (P=0.002, per protocol population). Investigator's assessment of cosmetic outcome was significantly better for MAL-PDT than cryotherapy (P<0.001), 79% of lesions having an excellent cosmetic outcome with MAL-PDT vs. 56% with cryotherapy at week 24. The cosmetic outcome achieved by MAL-PDT compared with cryotherapy was also preferred by patients (50% vs. 22%, respectively, P<0.001), and 59% of patients would prefer to have any new lesions treated with MAL-PDT compared with 25% with cryotherapy (P<0.001). Both treatment regimens were safe and well tolerated.MAL-PDT showed inferior efficacy for treatment of non-face/scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL-PDT conveyed the advantages of better cosmesis and higher patient preference.
The Hotel Study: Multimorbidity in a Community Sample Living in Marginal Housing
Authors: Fidel Vila-Rodriguez, William J. Panenka, Donna J. Lang, Allen E. Thornton, Talia Vertinsky, Hubert Wong, Alasdair M. Barr, Ric M. Procyshyn, J.J. Sidhu, Geoffrey N. Smith, T. Buchanan, Mel Krajden, Michael Krausz, Julio S. Montaner, G. William MacEwan, William G. Honer
Journal: American Journal of Psychiatry (2013)

The health of people living in marginal housing is not well characterized, particularly from the perspective of multimorbid illness. The authors investigated this population in a community sample.A prospective community sample (N=293) of adults living in single-room occupancy hotels was followed for a median of 23.7 months. Assessment included psychiatric and neurological evaluation, multimodal MRI, and viral testing.Previous homelessness was described in 66.6% of participants. Fifteen deaths occurred during 552 person-years of follow-up. The standardized mortality ratio was 4.83 (95% CI=2.91-8.01). Substance dependence was ubiquitous (95.2%), with 61.7% injection drug use. Psychosis was the most common mental illness (47.4%). A neurological disorder was present in 45.8% of participants, with definite MRI findings in 28.0%. HIV serology was positive in 18.4% of participants, and hepatitis C virus serology in 70.3%. The median number of multimorbid illnesses (from a list of 12) was three. Burden of multimorbidity was significantly correlated with lower role functioning score. Comorbid addiction or physical illness significantly decreased the likelihood of treatment for psychosis but not the likelihood of treatment for opioid dependence or HIV disease. Participants who died during follow-up appeared to have profiles of multimorbidity similar to those of the overall sample.This marginally housed cohort had greater than expected mortality and high levels of multimorbidity with adverse associations with role function and likelihood of treatment for psychosis. These findings may guide the development of effective health care delivery in the setting of marginal housing.
Electronic nose detects early stage and peripheral lung cancers
Authors: Annette Dent, Rayleen Bowman, Paul Zimmerman, Ian Yang, Kwun Fong
Journal: European Respiratory Journal (2012)

We have reported that exhaled volatile organic compound (eVOC) profile of lung cancer (LC) subjects differed from healthy ever smokers (HS).  Aim:  To determine if eVOC profile of LC subgroups (1) peripheral tumours and (2) early stage disease differ from HS.  Method : LC (n=53) and HS (n=177) subjects provided a breath sample after tidal breathing through an inspiratory port filter for 5 mins. It was analysed with a 32 sensor Cyranose 320 (Smiths Detection). Tumours were staged (7 th  ed TNM system), and defined as peripheral if located in the outer 1/3 of lung fields on axial CT images. LC subgroups were: Stages I/II (n=27), III/IV (n=25), central (n=32) and peripheral tumors (n=21). Data were reduced to principal components for canonical discriminant analysis to determine differences between groups. Accuracy was calculated using SPSS V17.0 with leave one out cross validation.  Results:  The eVOC profile distinguished between LC and HS with a cross validation (CVV) accuracy of 79%, (p Conclusion:  These data indicate the ability of exhaled breath VOC profiles to distinguish early stage and peripheral lung cancer cases from healthy ever smokers, and therefore support its potential as a non-invasive screening tool for early detection of lung cancer. Supported by The Prince Charles Hospital Foundation and Private Practice Trust Fund.
The Role of Chemokines in the Microenvironmental Control of T versus B Cell Arrest in Peyer's Patch High Endothelial Venules
Authors: R.A. Warnock, J.J. Campbell, M.E. Dorf, A. Matsuzawa, L.M. McEvoy, E.C. Butcher
Journal: The Journal of Experimental Medicine (2000)

Chemokines have been hypothesized to contribute to the selectivity of lymphocyte trafficking not only as chemoattractants, but also by triggering integrin-dependent sticking (arrest) of circulating lymphocytes at venular sites of extravasation. We show that T cells roll on most Peyer's patch high endothelial venules (PP-HEVs), but preferentially arrest in segments displaying high levels of luminal secondary lymphoid tissue chemokine (SLC) (6Ckine, Exodus-2, thymus-derived chemotactic agent 4 [TCA-4]). This arrest is selectively inhibited by functional deletion (desensitization) of CC chemokine receptor 7 (CCR7), the receptor for SLC and for macrophage inflammatory protein (MIP)-3β (EBV-induced molecule 1 ligand chemokine [ELC]), and does not occur in mutant DDD/1 mice that are deficient in these CCR7 ligands. In contrast, pertussis toxin–sensitive B cell sticking does not require SLC or MIP-3β signaling, and occurs efficiently in SLClow/− HEV segments in wild-type mice, and in the SLC-negative HEVs of DDD/1 mice. Remarkably, sites of T and B cell firm adhesion are segregated in PPs, with HEVs supporting B cell accumulation concentrated in or near follicles, the target domain of most B cells entering PPs, whereas T cells preferentially accumulate in interfollicular HEVs. Our findings reveal a fundamental difference in signaling requirements for PP-HEV recognition by T and B cells, and describe an unexpected level of specialization of HEVs that may allow differential, segmental control of lymphocyte subset recruitment into functionally distinct lymphoid microenvironments in vivo.
Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjögren's syndrome treated with rituximab
Authors: P M Meiners, S Arends, E Brouwer, F K L Spijkervet, A Vissink, H Bootsma
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To evaluate the responsiveness of the EULAR Sjögren9s Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren9s Syndrome Disease Activity Index (ESSDAI) in patients with primary Sjögren9s syndrome (pSS) treated with rituximab. <h3>Methods</h3> Twenty-eight patients with pSS treated with rituximab (1000 mg) infusions on days 1 and 15 were included in the study. Data were collected prospectively at baseline and 16, 24, 36, 48 and 60 weeks after treatment. Internal responsiveness was assessed using standardised response means (SRM) and effect sizes (ES). SRM and ES &lt;0.5, 0.5–0.8 and &gt;0.8 were interpreted as small, moderate and large, respectively. External responsiveness was assessed using Spearman correlation coefficients. <h3>Results</h3> Median (range) ESSPRI and ESSDAI scores at baseline were 6.7 (0.3–9.0) and 8 (2–18), respectively. Both indices improved significantly after treatment. SRM and ES values for ESSPRI and ESSDAI were ≥0.8 at week 16 and decreased afterwards, and were larger for ESSDAI than for ESSPRI. SRM and ES values for patient9s and physician9s global disease activity (GDA) and rheumatoid factor broadly followed the pattern of those of ESSPRI and ESSDAI. SRM and ES for stimulated whole salivary flow were small at all time points. At baseline and for most change scores, moderate to good correlations were found between ESSPRI and patient9s GDA and between ESSDAI and physician9s GDA. Poor association was found between ESSPRI and ESSDAI. <h3>Conclusions</h3> ESSPRI and ESSDAI are sensitive measures of change in disease activity after therapeutic intervention, which supports the usefulness of these indices for future clinical trials in patients with pSS. The responsiveness of ESSDAI was greater than that of ESSPRI.
Akt1-Mediated Fast/Glycolytic Skeletal Muscle Growth Attenuates Renal Damage in Experimental Kidney Disease
Authors: Shinsuke Hanatani, Yasuhiro Izumiya, Satoshi Araki, Taku Rokutanda, Yuichi Kimura, Kenneth Walsh, Hisao Ogawa
Journal: Journal of the American Society of Nephrology (2014)

Muscle wasting is frequently observed in patients with kidney disease, and low muscle strength is associated with poor outcomes in these patients. However, little is known about the effects of skeletal muscle growth per se on kidney diseases. In this study, we utilized a skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mouse model that promotes the growth of functional skeletal muscle independent of exercise to investigate the effects of muscle growth on kidney diseases. Seven days after Akt1 activation in skeletal muscle, renal injury was induced by unilateral ureteral obstruction (UUO) in Akt1 TG and wild-type (WT) control mice. The expression of atrogin-1, an atrophy-inducing gene in skeletal muscle, was upregulated 7 days after UUO in WT mice but not in Akt1 TG mice. UUO-induced renal interstitial fibrosis, tubular injury, apoptosis, and increased expression of inflammatory, fibrosis-related, and adhesion molecule genes were significantly diminished in Akt1 TG mice compared with WT mice. An increase in the activating phosphorylation of eNOS in the kidney accompanied the attenuation of renal damage by myogenic Akt1 activation. Treatment with the NOS inhibitor L-NAME abolished the protective effect of skeletal muscle Akt activation on obstructive kidney disease. In conclusion, Akt1-mediated muscle growth reduces renal damage in a model of obstructive kidney disease. This improvement appears to be mediated by an increase in eNOS signaling in the kidney. Our data support the concept that loss of muscle mass during kidney disease can contribute to renal failure, and maintaining muscle mass may improve clinical outcome.
Changes in body mass alone explain almost all of the variance in the serum sodium concentrations during prolonged exercise. Has commercial influence impeded scientific endeavour?
Authors: Timothy David Noakes
Journal: British Journal of Sports Medicine (2010)

In 1991, we provided definitive evidence that exercise-associated hyponatraemia (EAH) is caused by abnormal fluid retention in those who overdrink during prolonged exercise, but this finding was ignored. Instead, in 1996, influential guidelines of the American College of Sports Medicine (ACSM) promoted the concept that athletes should drink 'as much as tolerable' during exercise. What followed was an epidemic of cases of EAH and its associated encephalopathy (EAHE). A recent study funded by the sports drink industry confirms our 1991 finding by showing that 95% of the variance in the serum sodium concentration during exercise can be explained by changes in body mass alone. The possibility is that commercial influence delayed the acceptance of our findings for two decades.
Neutrophil elastase–mediated degradation of IRS-1 accelerates lung tumor growth
Authors: A McGarry Houghton, Danuta M Rzymkiewicz, Hongbin Ji, Alyssa D Gregory, Eduardo E Egea, Heather E Metz, Donna B Stolz, Stephanie R Land, Luiz A Marconcini, Corrine R Kliment, Kimberly M Jenkins, Keith A Beaulieu, Majd Mouded, Stuart J Frank, Kwok K Wong, Steven D Shapiro
Journal: Nature Medicine (2010)
Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound β-phenylethyl isothiocyanate
Authors: Yumin Hu, Weiqin Lu, Gang Chen, Hui Zhang, Yu Jia, Yue Wei, Hui Yang, Wan Zhang, Warren Fiskus, Kapil Bhalla, Michael Keating, Peng Huang, Guillermo Garcia-Manero
Journal: Blood (2010)