tbuckley/cabot-search huggingface dataset:
A160: Role of Interleukin-1 in Abnormal Monocyte Phenotype in Systemic Onset Juvenile Idiopathic Arthritis
Authors: Yujuan Zhang, Claudia Macaubas, Saloni Gupta, Clarissa Klein, Virginia Pascual, Arielle Hay, Susan D. Thompson, Christy I. Sandborg, Norman T. Ilowite, Elizabeth D. Mellins
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Monocytes phenotype changes in different microenvironments: the proinflammatory M1, regulatory M2, and M2-like phenotypes are each regulated by specific transcriptional factors (TFs). We have observed altered phenotypes in blood monocytes in systemic onset juvenile idiopathic arthritis (sJIA), including a decreased M1 cells, an increased mixed M1/M2 cells, and reduced secretion of IL-1, despite an increased IL-1b response to LPS (PMID 22281427). Here, we investigate whether these monocyte phenotypes are affected by IL-1 blockade. We analyzed monocytes from RAPPORT (RAndomized Placebo Phase study Of Rilonacept in the Treatment of sJIA) patients to determine levels of TFs involved in monocyte polarization and expression of genes related to IL-1 secretion, before and after treatment with Rilonacept, an IL-1 trap.



Methods:

Subjects on the Rilonacept arm received active drug from week 0 for a total of 24 weeks; subjects on the placebo arm received placebo for 4 weeks, then Rilonacept for 20 weeks. Blood samples were obtained at week 0, 2, 4, 14 and 24. We used real time PCR to measure M1 associated genes: Interferon Regulatory factor (IRF) family IRF5, STAT1; M2 associated genes IRF4, STAT6, Kruppel-Like Factor 4 (KLF4) and peroxisome proliferator-activated receptor-γ (PPAR-γ); IL-1 secretion related genes: RAB39, RAB27A, RAB27B, P2RX7, and IL-1β. All TFs levels were normalized by the average levels of 3 housekeeping genes.



Results:

30 non-paired RNA samples from 15 subjects were tested. Samples from subjects treated with Rilonacept for ≥10 weeks (Late RAPPORT) showed decreased expression of M2 genes, especially KLF4, compared to those untreated or treated for <10 weeks (Early RAPPORT) (Fig 1), except for PPAR-γ. Samples collected when there was clinical improvement also showed reduced KLF4 (Fig 2.). The expression of TFs following IL-1 inhibition in sJIA patients is distinct from normal controls. Levels of IL-1 secretion related genes, except for RAB27B, also were reduced in “Late RAPPORT” samples (Fig 3.).




Figure 1. 

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Figure 2. 

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Figure 3. 

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Conclusion:

IL-1 blockade in sJIA is likely associated with changes in the activation profile and expression of IL-1 secretion related genes in circulating monocytes. Monocytes phenotypes in treated subjects are not “normal” and likely reflect changes associated with compensated inflammation.
Prenatal Exposure to Wood Fuel Smoke and Low Birth Weight
Authors: Amna R. Siddiqui, Ellen B. Gold, Xiaowei Yang, Kiyoung Lee, Kenneth H. Brown, Zulfiqar A. Bhutta
Journal: Environmental Health Perspectives (2008)

BackgroundMaternal exposure to wood fuel smoke may lead to impaired fetal growth due to hypoxia and or oxidative stress from smoke constituents such as carbon monoxide and particulate matter.ObjectivesWe studied the risk of low birth weight (LBW) and reduced mean birth weight in relation to reported use of wood for cooking during the prenatal period, compared with natural gas (NG).MethodsWe studied a historical cohort of women who had a singleton live birth in the years 2000–2002, from a semirural area of Pakistan. Infant's birth weight was obtained from records, and prenatal records had data for maternal body mass index and parity. Cooking habits, daytime sleep habits, and type of fuel used during the pregnancies in 2000–2002 were ascertained by a survey done in 2004–2005. We performed multiple linear and logistic regression modeling using propensity scores to adjust for confounding variables.ResultsUnadjusted mean (± SD) birth weight was 2.78 ± 0.45 kg in wood users, and 2.84 ± 0.43 kg (p < 0.06) in NG users. Infants born to wood users averaged 82 g lighter than infants born to NG users when weight was adjusted for confounders (p < 0.07). The rate of LBW (< 2,500 g) was 22.7% among wood users compared with 15.0% in NG users (p < 0.01), for an adjusted relative risk of 1.64 (95% confidence interval, 1.10–2.34). The population attributable risk for LBW explained by wood use was estimated to be 24%.ConclusionCooking with wood fuel during pregnancy, a potentially modifiable exposure, was associated with LBW and marginally lower mean birth weight compared with using NG.
IMPAIRED VENTILATION AND DRAINAGE OF THE NOSE THE MOST COMMON CAUSES OF NASAL CATARRH.
Authors: EDWIN PYNCHON
Journal: JAMA (1897)

In conclusion, I would urge the systematic examin- ation of the eyes of children, both for motor and visual symptoms, in all conditions simulating menin- gitis, especially in those cases where there has been a long standing middle ear suppuration, in cases of pneumonia, pyemia, empyema, septicemia, etc., and cases giving tubercular history and with glandular complications.At times in these cases the eye con- ditions are the only symptoms pointing conclusively to brain complication.
THE RELATIONSHIP OF BLOOD URIC ACID CONTENT TO THE STATE OF RENAL FUNCTION IN NEPHRITIS
Authors: Christopher Johnston
Journal: Journal of Clinical Investigation (1931)

In a recent paper from this laboratory (1) the blood urea clearance test was compared in nephritic subjects with other measures of renal function, namely, the concentrations of urea, creatinine, and hemo- globin in the blood, and the two-hour excretion of phenolsulphonephthalein.In the present paper the blood urea clearance test is simi- larly compared with the concentration of uric acid in the blood.After the introduction of Folin's micro methods of blood analysis, some evidence accumulated to show that in the course of a progres- sive nephritis, uric acid was the first nitrogenous waste product to be increased in the blood, and that its estimation could be used as the most delicate indicator of early impairment of renal function (2, 3).At the same time, it was appreciated that in the terminal stages of nephritis the increase of uric acid did not parallel the increase of the creatinine, nonprotein nitrogen, or urea (4).It was subsequently shown that in patients with essential hypertension the blood uric acid was often distinctly elevated, and bore no prognostic signifi- cance (5).Hitzenberger and Richter-Quittner (6) found in two such patients that the endogenous excretion of uric acid was slightly above normal, and that they responded to high purine diets by the prompt excretion of large amounts of uric acid.Further doubt was then cast on the validity of the blood uric acid determination as an index of renal function by reports of its increase in many unrelated conditions.Gout, leukemia, and pneumonia had for many years been known to cause this increase, but newer work indicated that in addition, a rise in the level of blood uric acid could be found in pernicious anemia (7), carbon monoxide poisoning (8), toxemias of pregnancy (9), erythemia (10), eczema (11), and during 555
Allergen-specific IgG1 and IgG3 through Fc gamma RII induce eosinophil degranulation.
Authors: M Kaneko, M C Swanson, G J Gleich, H Kita
Journal: Journal of Clinical Investigation (1995)

Evidence suggests that eosinophils contribute to inflammation in bronchial asthma by releasing chemical mediators and cytotoxic granule proteins. To investigate the mechanism of eosinophil degranulation in asthma, we established an in vitro model of allergen-induced degranulation. We treated tissue culture plates with short ragweed pollen (SRW) extract and sera from either normal donors or SRW-sensitive patients with asthma. Eosinophils were incubated in the wells and degranulation was assessed by measurement of eosinophil-derived neurotoxin in supernatants. We detected degranulation only when sera from SRW-sensitive patients were reacted with SRW. Anti-IgG and anti-Fc gamma RII mAb, but not anti-IgE or anti-Fc epsilon RII mAb, abolished the degranulation. IgG-depleted serum did not induce degranulation; IgE-depleted serum triggered as much degranulation as untreated serum. Furthermore, serum levels of SRW-specific IgG1 or IgG3 correlated with the amounts of released eosinophil-derived neurotoxin. When eosinophils were cultured in wells coated with purified IgG or IgE, eosinophil degranulation was observed only with IgG. Finally, human IgG1 and IgG3, and less consistently IgG2, but not IgG4, induced degranulation. Thus, sera from patients with SRW-sensitive asthma induce eosinophil degranulation in vitro through antigen-specific IgG1 and IgG3 antibodies. These antibodies may be responsible for degranulation of eosinophils in inflammatory reactions, such as bronchial asthma.
Taking medicines: concordance is not compliance
Authors: D. Dickinson, P. Wilkie, M. Harris
Journal: BMJ (1999)

EDITOR—Consultations between patients and doctors most often involve two contrasting sets of health beliefs. Concordance recognises that the health beliefs of the patient, although different from those of the doctor, nurse, or pharmacist, are no less cogent or important when making decisions about the best approach to the treatment of the individual.

In October 1998 the Concordance Coordinating Group, chaired by Marshall Marinker, was formed to take forward the programme of work outlined in a 1997 report. …
Interaction Effects of Ultrafine Carbon Black with Iron and Nickel on Heart Rate Variability in Spontaneously Hypertensive Rats
Authors: Chuen-Chau Chang, Jing-Shiang Hwang, Chang-Chuan Chan, Tsun-Jen Cheng
Journal: Environmental Health Perspectives (2007)

Particulate matter (PM) has been reported to be associated with alterations in heart rate variability (HRV); however, the results are inconsistent. We propose that different components of PM cause the discrepancy.In this study, our goal was to determine whether different types of exposure would cause different HRV effects, and to verify the interactions between co-exposing components.Ultrafine carbon black (ufCB; 14 nm; 415 microg and 830 microg), ferric sulfate [Fe(2)(SO(4))(3); 105 microg and 210 microg], nickel sulfate (NiSO(4); 263 mug and 526 microg), and a combination of high-dose ufCB and low-dose Fe(2)(SO(4))(3) or NiSO(4) were intratracheally instilled into spontaneously hypertensive rats. Radiotelemetry data were collected in rats for 72 hr at baseline and for 72 hr the following week to determine the response to exposure. Effects of exposure on 5-min average of normal-to-normal intervals (ANN), natural logarithm-transformed standard deviation of the normal-to-normal intervals (LnSDNN), and root mean square of successive differences of adjacent normal-to-normal intervals (LnRMSSD) were analyzed using self-control experimental designs.Both high- and low-dose ufCB decreased ANN marginally around hour 30, with concurrent increases of LnSDNN. LnRMSSD returned to baseline levels after small initial increases. We observed minor effects after low-dose Fe and Ni instillation, whereas biphasic changes were noted after high-dose instillations. Combined exposures of ufCB and either Fe or Ni resulted in HRV trends different from values estimated from individual-component effects.Components in PM may induce different cardioregulatory responses, and a single component may induce different responses during different phases. Concurrent exposure to ufCB and Fe or Ni might introduce interactions on cardioregulatory effects. Also, the effect of PM may be mediated through complex interaction between different components of PM.
Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs
Authors: S Nattel
Journal: Cardiovascular Research (1998)

The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved antiarrhythmic drug therapy to be developed, it is essential to understand the fundamental mechanisms that cause proarrhythmic reactions to antiarrhythmic drugs. The present article reviews the experimental evidence that has been obtained regarding the mechanisms of proarrhythmia. The evidence available provides important insights, and points to potential strategies for developing newer and safer antiarrhythmic compounds.
TCTAP A-077 IVUS Guided Minimum Contrast PCI for CKD Patients
Authors: Yoshifumi Hano, Nakamura Shigeru, Tomoko Kobayashi, Atsushi Funatsu, Masahiro Mizobuchi, Hideaki Takahashi, Munemitsu Otagaki, Satoru Sasaki
Journal: Journal of the American College of Cardiology (2014)
Critical Role of STAT5 Transcription Factor Tetramerization for Cytokine Responses and Normal Immune Function
Authors: Jian-Xin Lin, Peng Li, Delong Liu, Hyun Tak Jin, Jianping He, Mohammed Ata Ur Rasheed, Yrina Rochman, Lu Wang, Kairong Cui, Chengyu Liu, Brian L. Kelsall, Rafi Ahmed, Warren J. Leonard
Journal: Immunity (2012)
Hypertension in renal allograft recipients may be conveyed by cadaveric kidneys from donors with subarachnoid haemorrhage.
Authors: S Strandgaard, U Hansen
Journal: BMJ (1986)

Evidence for hypertension was sought retrospectively in the necropsy records of 37 cadaveric kidney donors who had died of subarachnoid haemorrhage and 41 donors who had died of head injury, cerebral tumour, or (in a few instances) other causes. Mean relative heart weight in the donors with subarachnoid haemorrhage was 0.58 (1 SD = 0.09)% and in the other donors 0.52 (0.09)% (p less than 0.01), a difference unexplained by any factor other than a comparatively higher blood pressure in the donors who had died of subarachnoid haemorrhage. Blood pressure was analysed over 72 months after renal transplantation in 23 recipients with normal or near normal graft function and no evidence of chronic rejection or graft artery stenosis. Twelve patients who had received kidneys from donors with subarachnoid haemorrhage had consistently higher systolic blood pressures (p less than 0.004) and needed more antihypertensive treatment (p less than 0.0004) than the 11 recipients of kidneys from donors who had died of head injury or cerebral tumour. These observations suggest that cadaveric kidneys from donors dying of subarachnoid haemorrhage may induce or sustain hypertension after transplantation.
Impact of Blockade of Histamine H2Receptors on Chronic Heart Failure Revealed by Retrospective and Prospective Randomized Studies
Authors: Jiyoong Kim, Akiko Ogai, Satoshi Nakatani, Kazuhiko Hashimura, Hideaki Kanzaki, Kazuo Komamura, Masanori Asakura, Hiroshi Asanuma, Soichiro Kitamura, Hitonobu Tomoike, Masafumi Kitakaze
Journal: Journal of the American College of Cardiology (2006)
Comparison of the Seasonal Pattern in the Clinical Onset of IDDM in Finland and Sardinia
Authors: Marjatta Karvonen, Virva Jäntti, Sandro Muntoni, Marco Stabilini, Liliana Stabilini, Sergio Muntoni, Jaakko Tuomilehto
Journal: Diabetes Care (1998)

OBJECTIVE To examine the seasonal pattern for the clinical onset of IDDM in Finland and Sardinia, two areas where the incidence of IDDM is the highest in the world, and to determine the effect of climate and temperature on the clinical onset of IDDM. RESEARCH DESIGN AND METHODS Analysis of seasonality for the diagnosis of IDDM was based on 1,405 cases in Finland and 425 cases in Sardinia diagnosed at ≤14 years of age from 1989 to 1992. The average annual incidence of IDDM was 36.4/100,000 in Finland and 34.4/100,000 in Sardinia. Seasonal patterns were estimated presenting the data as short Fourier series up to three harmonics together with a possible linear trend. Likelihood ratio tests and Akaike's information criterion were used to determine the number of harmonics necessary to model the seasonal pattern. Seasonal patterns in both countries were compared between sexes and between the three 5-year age-groups, each controlling for the other's effect. RESULTS In both countries, a significant seasonal pattern during a calendar year was found for the sexes combined and for two age-groups (0–9 and 10–14 years). In Sardinia, two distinct cycles were found in the younger age-group, with a decreased incidence during May through August and an increased incidence during the autumn months. Two cycles were apparent in the older age-group, with the nadir occurring during June through September. In Finland, one cycle was found in the younger age-group, with a decreased incidence in June. In the older age-group, there were two distinct cycles, with a decreased incidence in June and in the September through December period. CONCLUSIONS Differences between Finland and Sardinia in the seasonal pattern for the incidence of newly diagnosed IDDM cannot be explained by differences in climate, temperature, a longer warm period in Sardinia, or other climatic phenomena. The results do not provide evidence in favor of a specific viral etiology of IDDM. It may be suggested that there are triggering events at certain times, but they are likely to be unspecinc. Nevertheless, why the incidence of IDDM in these two populations is equally high despite differences in climate, environment, and genetic background remains an unsolved question.
Why Don’t Physicians (and Patients) Consistently Follow Clinical Practice Guidelines?
Authors: Donald E. Casey
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
Rectal Bleeding and Indomethacin
Authors: J. Walls, D. Bell, W. Schorr
Journal: BMJ (1968)

<h3>BACKGROUND:</h3> We evaluated the outcome of subjects with ARDS in relation to etiology and severity in a retrospective cohort study of the ARDS Network randomized controlled trials. The primary outcome was 28-d mortality. The secondary outcomes were 60-d mortality and ventilator- and ICU-free days. For severity of ARDS, subjects were stratified according to <b>P</b><sub>aO2</sub>/<b>F</b><sub>IO2</sub>. The etiology of ARDS was classified into sepsis, pneumonia, aspiration, trauma, and others. <h3>RESULTS:</h3> A total of 2,914 subjects were included in these trials. Outcomes were modeled with multivariable regressions adjusted for baseline covariates, age, sex, race, Acute Physiology and Chronic Health Evaluation III (APACHE III), vasopressor use, modified lung injury score, diabetes mellitus, cancer status, body mass index, pre-ICU location, ICU location, and study. There was no statistically significant difference in 28-d mortality in relation to ARDS severity. Subjects with trauma, compared with other etiologies of ARDS, had significantly lower mortality at 28 d (odds ratio [OR] = 0.47, 95% CI 0.26−0.83, <i>P</i> = .01). Sixty-day mortality was significantly lower for trauma subjects and those with severe ARDS group (OR = 0.5, 95% CI 0.3−0.85, <i>P</i> = .01 and OR = 0.71, 95% CI 0.52−0.98, <i>P</i> = .034, respectively). There were statistically significantly more ICU-free days and ventilator-free days for the aspiration group (OR = 1.09, 95% CI 1.02−1.17, <i>P</i> = .01 and OR = 1.09, 95% CI 1.02−1.16, <i>P</i> = .01, respectively). There was no statistically significant difference in ICU-free days or ventilator-free days in relation to severity of ARDS. <h3>CONCLUSIONS:</h3> Severity of ARDS based on <b>P</b><sub>aO2</sub>/<b>F</b><sub>IO2</sub> did not impact 28-d mortality, ventilator-free days, or ICU-free days. Among the etiologies of ARDS, trauma subjects had the lowest 28- and 60-d mortality, whereas subjects with aspiration had more ICU-free days and ventilator-free days.
Abstract 3239: Shp2 inhibitor activity of estramustine phosphate and its triterpenoid analogues
Authors: Latanya M. Scott, Liwei Chen, Kenyon G. Daniel, Murali K. Urlam, Wesley H. Brooks, Wayne C. Guida, Harshani R. Lawrence, Said M. Sebti, Nicholas J. Lawrence, Jie Wu
Journal: Cancer Research (2011)

Abstract Shp2 is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene. Shp2 mediates proliferative signaling induced by growth factors. Gain-of-function PTPN11 mutations that encode constitutively active Shp2 are leukemic oncogenes. In a continuing effort to identify new Shp2 PTP inhibitors, we screened a small molecule library comprising the National Cancer Institute (NCI) Approved Oncology Drug set and the NIH Clinical Collection. After evaluation of initial hits, estramustine phosphate was verified as a Shp2 PTP inhibitor. A focused structure-activity relationship study indicated that the 17-phosphate group is required for the Shp2 PTP inhibitor activity of estramustine phosphate. A search for estramustine phosphate analogs led to identification of two triperpenoids, enoxolone and celastrol, having Shp2 PTP inhibitor activity. With the previously reported PTP1B inhibitor trodusquemine, our study reveals steroids and triterpenoids with negatively charged phosphate, carboxylate, or sulfonate groups as novel pharmacophores of selective PTP inhibitors. These findings point to a rich natural source for discovery of lead compounds of novel PTP inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3239. doi:10.1158/1538-7445.AM2011-3239
Extramedullary plasmacytoma of the colon: a rare cause of gastrointestinal bleeding
Authors: D. Collado Pacheco, M. Moran Ortiz de Solórzano, E. Quintanilla Lázaro, I. Chico Álvarez, L. Rábago Torre
Journal: Endoscopy (2009)

A 74-year-old man presented with a 48-hour history of diarrhea, abdominal pain, and rectal bleeding. He was known to have multiple myeloma, which had been diagnosed in 2001. Although complete remission was achieved after chemotherapy, the patient had two relapses: a malignant pericardial effusion (2003) and bone marrow relapse (May, 2008). Initial evaluation revealed an abdominal mass on the right side, hematochezia, hemoglobin level of 11.4 g/dL, and abnormal renal function. Urgent colonoscopy disclosed pseudomembranous colitis in the left colon, and the hepatic flexure was stiff. A large number of coalescent intracolonic masses were found, covered in some places by ulcerated mucosa with fibrin ([Fig. 1]).