tbuckley/cabot-search huggingface dataset:
Association of<i>STAT4</i>,<i>IRF5</i>and<i>BLK</i>polymorphisms with severity and outcome in lupus nephritis
Authors: Karin G Eriksson, Agneta Zickert, Johanna K Sandling, Andreas Jönsen, Lars Rönnblom, Timothy W Behrens, Robert R Graham, Ward Ortmann, Ann-Christine Syvänen, Iva Gunnarsson, Gunnel Nordmark
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Lupus nephritis (LN) is a cause of significant morbidity and mortality and occurs in 15–50% of patients with SLE. Proliferative nephritis is most severe and 10% of LN patients develop end stage renal disease (ESRD). Several susceptibility genes for SLE have been identified where an association with LN has been shown for SNPs in <i>STAT4</i> and <i>ITGAM</i>. The aim of this investigation was to analyse the genetic data from a previous study1 for association with LN, in particular proliferative nephritis and ESRD. <h3>Materials and methods</h3> The authors included 567 Swedish Caucasian patients with SLE and 512 matched controls. All samples had been genotyped on a custom array 12K chip1. A total of 195 (34.4%) patients had a history of LN. Renal biopsies were available from 153 patients where 92 (60.1%) showed a proliferative nephritis. During follow-up (median 14 years, range 0–46), 11.1% reached ESRD. Case-control association analyses were performed for patients with LN, proliferative nephritis, ESRD and for comparison all SLE patients, versus controls. <h3>Results</h3> The authors detected strong signals of association between SNPs in <i>STAT4</i> (OR 2.2, 95% CI 1.7 to 2.8), <i>IRF5</i> (OR 2.0, 95% CI 1.5 to 2.7) and a marker for <i>HLA-DR3</i> (OR 1.95, 95% CI 1.4 to 2.6), in the analysis of LN patients versus controls (all p&lt;0.0001). In addition, six genes showed an association with LN with OR 1.5-2.2, p&lt;0.001 (<i>PMS2, TNIP1, CARD11, ITGAM, BLK</i> and <i>IRAK1</i>). When analysing only the patients with proliferative nephritis versus controls the OR for association increased for <i>STAT4, IRF5</i> and <i>BLK</i> to 2.4, 2.2 and 1.7 respectively (all p&lt;0.01). For patients in ESRD the OR for <i>STAT4, IRF5</i> and <i>BLK</i> increased further to 2.9, 3.1 and 2.1 whereas the OR for association with the <i>HLA-DR3</i> marker was decreased to 1.7. The association between the risk alleles in <i>IRF5, STAT4</i> and <i>BLK</i> and LN phenotypes was stronger than the association to SLE per se. <h3>Conclusions</h3> Risk alleles in <i>STAT4, IRF5</i> and <i>BLK</i> are associated with an increased risk for LN. The association with proliferative nephritis was particularly strong and the risk of developing ESRD was even more striking. On the contrary, the HLA-DR3 marker did not display a strong association with LN. The authors conclude that variations in genes in immunological pathways predispose to LN severity and renal outcome.
Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission
Authors: David I. Marks, Waleska S. Pérez, Wensheng He, Mei-Jie Zhang, Michael R. Bishop, Brian J. Bolwell, Christopher N. Bredeson, Edward A. Copelan, Robert Peter Gale, Vikas Gupta, Gregory A. Hale, Luis M. Isola, Ann A. Jakubowski, Armand Keating, Thomas R. Klumpp, Hillard M. Lazarus, Jane L. Liesveld, Richard T. Maziarz, Philip L. McCarthy, Mitchell Sabloff, Gary Schiller, Jorge Sierra, Martin S. Tallman, Edmund K. Waller, Peter H. Wiernik, Daniel J. Weisdorf
Journal: Blood (2008)
Nasal mucosal histamine reactivity among young students and teachers, having no or prolonged exposure to a deteriorated indoor climate
Authors: S. Rudblad, K. Andersson, L. Bodin, G. Stridh, J. E. Juto
Journal: Allergy (2002)

Background: In a study performed in the spring of 1995, we found a significantly greater nasal mucosal histamine reactivity among teachers, who had worked for several years in a recently renovated moisture‐damaged school, than in those in a control school. In the present study we investigated the students who begun their high‐school studies at both schools in the autumn of 1995 and compared them with the teachers as regards mucosal reactivity, atopy and symptoms. Methods: Twenty‐eight teachers in the target school, 18 teachers in the control school and 45 students from each school underwent a nasal histamine provocation test and a skin‐prick test. They also answered a standardized questionnaire. Results: The teachers in both schools had more marked nasal mucosal histamine reactivity at the lowest provocation concentrations than the students. The histamine provocation curve of the target school teachers had consistently higher values than that of the students ( P = 0.0001), but its slope and shape were similar ( P = 0.15), while the slope of the provocation curve of the control school teachers was flatter. However, there was only a borderline significance in this respect compared to the students ( P = 0.07). Teachers with a dry and crusty appearance of the nasal mucosa on anterior rhinoscopy reacted more strongly to histamine provocation than those without this finding ( P = 0.0004). There was a significantly higher frequency of skin‐prick test positivity (SPT+) among the students ( P = 0.03). There were no significant differences in nasal mucosal histamine reactivity between atopic and non‐atopic subjects out of pollen season. Conclusions: Teachers had a significantly greater mucosal histamine reactivity than the students, whereas the latter had a significantly higher frequency of atopy. These results are compatible with an age‐related pattern of mucosal reactivity. A crusty appearance of the nasal mucosa seems to predispose to an increase in histamine reactivity. There were no significant differences according to histamine reactivity between atopic and non‐atopic subjects.
The pill: safe sex and Crohn’s disease?
Authors: E M ALSTEAD
Journal: Gut (1999)

See article on page 218 

Epidemiological data suggest that there is a small increase in the risk of Crohn’s disease in women who use the combined oral contraceptive pill,1-3 the relative risk being about twofold. On this basis, many physicians advise women with Crohn’s disease not to use this form of contraception. Is there really sufficient evidence to justify this advice? Unlike smoking,1 there is no clear evidence of an association between oral contraceptive use and the prevalence of Crohn’s disease. The available data are confounded by problems with study design and also the influence of smoking, as some studies have shown that smokers are more likely to use oral contraception. There is little information on whether the type of oral contraception may explain some of the differences observed, in particular the oestrogen dose and the length of use.

Patients with active inflammatory bowel disease are at increased risk of developing thromboembolic disease and there are also theoretical reasons to suppose that the pill might precipitate or exacerbate Crohn’s disease. High dose oral contraceptives, containing more than 50 …
Does Bereavement-Related Major Depression Differ From Major Depression Associated With Other Stressful Life Events?
Authors: Kenneth S. Kendler, John Myers, Sidney Zisook
Journal: American Journal of Psychiatry (2008)

Objective: Of the stressful life events influencing risk for major depression, DSM-III and DSM-IV assign a special status to bereavement. A depressive episode that is bereavement-related and has clinical features and course characteristic of normal grief is not diagnosed as major depression. This study evaluates the empirical validity of this exclusion criterion. Method: To determine the similarities of bereavement-related depression and depression related to other stressful life events, the authors identified and compared cases on a range of validators in a large-population-based sample of twins. The authors evaluated whether cases of bereavement-related depression that also met DSM criteria for “normal grief” were qualitatively distinct from other depressive cases. Results: Eighty-two individuals with confirmed bereavement-related depression and 224 with confirmed depression related to other stressful life events were identified. The two groups did not differ in age at onset of major depression, number of prior episodes, duration of index episode, number of endorsed “A criteria,” risk for future episodes, pattern of comorbidity, levels of extraversion, risk for major depression in their co-twin, or the proportion meeting criteria for “normal grief.” However, individuals with bereavement-related depression were slightly older, and more likely to be female, and had lower levels of neuroticism, treatment-seeking, and guilt and higher levels of fatigue and loss of interest. Interaction analyses failed to find unique features of people whose illness met criteria for both bereavement-related depression and normal grief compared to those whose illness was related to other life stressors. Conclusions: The similarities between bereavement-related depression and depression related to other stressful life events substantially outweigh their differences. These results question the validity of the bereavement exclusion for the diagnosis of major depression.
Identification and quantitation of embryonic and three types of fetal hemoglobin produced on induction of the human pluripotent leukemia cell line K‐562 with hemin
Authors: J. E. Fuhr, E. Bamberger, C. B. Lozzio, B. B. Lozzio, A. E. Felice, G. Altay, B. B. Webber, A. L. Reese, S. M. Mayson, T. H. J. Huisman
Journal: American Journal of Hematology (1982)

Abstract The hemoglobins synthesized by the pluripotent K‐562 leukemia cell line of human origin after induction with hemin have been isolated by DEAE‐cellulose chromatography and characterized by electrophoresis, high pressure liquid chromatography, and a radio‐immunological assay. Six hemoglobin zones have been observed with the following likely compositions. Zone 1: α 2 ϵ 2 , or Hb Gower‐2; zone 2: ζ 2 ϵ 2 , or Hb Gower‐1; zone 3: ζ 2 γ 2 , or Hb Portland‐I; zone 4: Hb F, or α 2 γ 2 ; zone 5: a mixture of acetylated Hb Portland‐I and Hb F; zone 6: Hb Bart's, or γ 4 . The embryonic Hbs (zones 1, 2, and 3) constituted 50%–75% of the total Hb present; the quantities varied from one experiment to the other. Both Hb Gower‐1 and Hb Gower‐2 were present. The γ chain was heterogeneous and contained the G γ , A γ I , and A γ T types in a ratio of about 4:2:1, indicating a heterozygosity for the Ile → Thr substitution at position γ75. The methodology used can be applied for additional studies evaluating quantitative changes in Hb types due to in vitro manipulations.
Increased nitric oxide synthase activity as a cause of mitochondrial dysfunction in rat hepatocytes: roles for tumor necrosis factor ?
Authors: I Kurose, S Miura, H Higuchi, N Watanabe, Y Kamegaya, M Takaishi, K Tomita, D Fukumura, S Kato, H Ishii
Journal: Hepatology (1996)

Kupffer cells have been implicated in playing an important role in the pathogenesis of endotoxemia–associated liver injury. The present study was designed to investigate whether Kupffer cell–derived mediators alter the mitochondrial oxidative phosphorylation of hepatocytes in the endotoxemic condition. Liver cells were isolated from male Wistar rats. Oxidative phosphorylation was monitored as the fluorescence of rhodamine 123 (Rh123), which is the fluorescent cationic dye used to indicate mitochondrial energy synthesis. Two hours after coculture of hepatocytes with lipopolysaccharide (LPS)–pretreated Kupffer cells, a marked decrease in hepatocyte rhodamine 123 fluorescence was observed. The hepatocyte mitochondrial dysfunction was attenuated by the addition of either NG–monomethyl–l–arginine (l–NMMA), an inhibitor of nitric oxide (NO) synthesis, or aminoguanidine, an inducible–type of NO synthase inhibitor, to the culture medium of cocultures, to the pretreatment of LPS–activated Kupffer cells with antisense oligodeoxynucleotides against iNOS messenger RNA (mRNA), or to tumor necrosis factor α (TNF–α) mRNA. Four hours after the coculture, hepatocyte Rh123 fluorescence further decreased, and an iNOS induction as well as an increased NO production were observed in hepatocytes that were cocultured with LPS–pretreated Kupffer cells. The membrane barrier dysfunction of hepatocytes, indicated by propidium iodide staining, was also induced by a 4–hour coculture with LPS–pretreated Kupffer cells. These late–phase changes were inhibited either by the pretreatment of hepatocytes with antisense oligodeoxynucleotides against iNOS mRNA or by treatments that are effective in the early phase (within 2 hours). Incubation with recombinant rat TNF–α decreased hepatocyte Rh123 fluorescence within 2 hours. Thus, the present study suggests that NO and TNF–α released from LPS–pretreated Kupffer cells directly inhibit the hepatocyte mitochondrial function in the early phase, and then NO synthesized by TNF–α–induced hepatocyte iNOS causes lethal hepatocyte injury, characterized by diminished mitochondrial energization and membrane barrier function in the late phase.
The α6β4 Integrin Can Regulate ErbB-3 Expression: Implications for α6β4 Signaling and Function
Authors: Valentina Folgiero, Robin E. Bachelder, Giulia Bon, Ada Sacchi, Rita Falcioni, Arthur M. Mercurio
Journal: Cancer Research (2007)

Abstract The integrin α6β4 has been shown to facilitate key functions of carcinoma cells, including their ability to migrate, invade, and evade apoptosis. The mechanism involved seems to be a profound effect of α6β4 on specific signaling pathways, especially the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. An intimate relationship between α6β4 and growth factor receptors may explain this effect of α6β4 on signaling. Previously, we showed that α6β4 and ErbB-2 can function synergistically to activate the PI3K/Akt pathway. Given that ErbB-2 can activate PI3K only when it heterodimerizes with other members of the epidermal growth factor receptor family, these data imply that other receptors cooperate in this process. Here, we report that α6β4 can regulate the expression of ErbB-3 using several different models and that the consequent formation of an ErbB-2/ErbB-3 heterodimer promotes the α6β4-dependent activation of PI3K/Akt and the ability of this integrin to impede apoptosis of carcinoma cells. Our data also support the hypothesis that α6β4 can regulate ErbB-3 expression at the translational level as evidenced by the findings that α6β4 does not increase ErbB-3 mRNA significantly, and that this regulation is both rapamycin sensitive and dependent on eukaryotic translation initiation factor 4E. These findings provide one mechanism to account for the activation of PI3K by α6β4 and they also provide insight into the regulation of ErbB-3 in carcinoma cells. [Cancer Res 2007;67(4):1645–52]
The William Osler lecture series. Continuing medical education in letters and science
Authors: J. M. Nelson
Journal: JAMA (1982)

SIR William Osler (1849-1919), the renowned clinician, educator, and philosopher, firmly believed that the complete physician must have interests outside the profession of medicine. For Osler, incessant concentration of thought on one subject, no matter how interesting, "tethered a man's mind in a narrow field."<sup>1(p112)</sup>Osler well understood the vital role the humanities could play in relieving the tedium of a physician's preoccupation with medicine. For Osler, the humanities were "the hormones" with which to facilitate "daily intercourse with some of the great minds of the ages."<sup>1(pp80-82)</sup>It is clear from Osler's philosophy and personal example that he thoroughly appreciated the importance of a broad-based curriculum for a physician's lifelong education. Unfortunately, in modern medical education the humanities may too often be sacrificed on the altar of technical expertise. The result is that too many physicians fall into a lifelong pattern of narrowly focused interests. Reporting the results
Search for the preadipocyte progenitor cell
Authors: Gary J. Hausman, Dorothy B. Hausman
Journal: Journal of Clinical Investigation (2006)

An increase in adipocyte number is a major contributor to the increase in adipose tissue mass that is characteristic of obesity. The identity and regulation of the adipocyte precursor cell (or preadipocyte) and the preadipocyte precursor cell (or progenitor cell) have been intensely studied for many years. In this issue of the JCI, Crossno et al. report that progenitor cells originating from outside the adipose tissue, in particular the bone marrow, can contribute to an increase in adipocyte number (see the related article beginning on page 3220). Their study in mice reveals that treatment with the thiazolidinedione rosiglitazone or exposure to a high-fat diet promotes the trafficking of circulating bone marrow–derived progenitor cells into adipose tissue, where they become multilocular adipocytes. This adds a new and unexpected dimension to this research arena.
<i>Chicken in Sunrise</i>
Authors: Jeanette M. Smith
Journal: JAMA (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 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
From Histones to Ribosomes: A Chromatin Regulator Tangoes with Translation
Authors: Scott B. Rothbart, Bradley M. Dickson, Brian D. Strahl
Journal: Cancer Discovery (2015)

Abstract Summary: Histone lysine methylation is a critical regulator of chromatin-templated processes such as gene transcription and DNA repair, and is dynamically controlled by enzymes that write and erase this posttranslational modification. Although histone methylation has been well studied, the functions of nonhistone lysine methylation and its regulatory enzymes, particularly outside the nucleus, are poorly defined. In this issue of Cancer Discovery, Van Rechem and colleagues shed light on a new role for the lysine demethylase KDM4A as a regulator of protein translation and identify a single-nucleotide polymorphism in the KDM4A gene as a candidate biomarker for mTOR inhibitor therapy. Cancer Discov; 5(3); 228–30. ©2015 AACR. See related article by Van Rechem and colleagues, p. 245 See related article by Van Rechem and colleagues, p. 255
Peeling the onion: NMDA dysfunction as a unifying model in schizophrenia
Authors: Daniel C. Javitt
Journal: Behavioral and Brain Sciences (2003)

Abstract N -methyl-d-aspartate receptor (NMDAR) dysfunction plays a crucial role in schizophrenia, leading to impairments in cognitive coordination. NMDAR agonists (e.g., glycine) ameliorate negative and cognitive symptoms, consistent with NMDAR models. However, not all types of cognitive coordination use NMDAR. Further, not all aspects of cognitive coordination are impaired in schizophrenia, suggesting the need for specificity in applying the cognitive coordination construct.
Commentary: we need to be better prepared for a technological future
Authors: Bertalan Mesko
Journal: BMJ (2015)

A few times a week, I put a small device into a pocket on a wristband and measure my sleep pattern. I use the results to set my smart watch to wake me up at the optimum time (when I start moving and I’m not in deep sleep any more). That way I wake up energised. When I go out for a run I collect data with activity trackers and wear a chest strip to chart my heart rate to motivate me to improve my performance. Once a week, I measure my blood pressure, and I can do an echocardiogram at home. From home I also access the peer reviewed literature and look at information sourced from my curated social media channels. For relaxation I use a device that gives feedback about my brain activity, and I improve my cognitive …
ON THE EARLY RECOGNITION AND TREATMENT OF ACUTE INTESTINAL OBSTRUCTION
Authors: J. Hartley
Journal: BMJ (1909)

T7HE following case came under my care recently, and X thought it worth recording, owing to the apparently elight injury that caused it., was called on October 18th, 1909, to see a girl aged 13, and found her fully dressed reclining on a coueh by the fire in the tsitting-room of a cottage house.She looked pale and very thin, but sat up shortly after I entered.The pulse was 96, temperature normal.She was suffering from nausea.The
Treatment of basal cell carcinoma by dermatologists in the United Kingdom
Authors: R.J MOTLEY, D.J GOULD, W.S DOUGLAS, N.B SIMPSON
Journal: British Journal of Dermatology (1995)

Details of presentation and treatment were obtained prospectively by questionnaire for 1366 patients with basal cell carcinoma, first attending under the care of 166 consultant dermatologists in the U.K., during a 2-week period. One thousand five hundred and ninety-seven tumours were reported in these patients (median age 71 years). Most were situated on the head and neck, and their median size was 9 mm. Excision was the most common treatment used in 58% of tumours, curettage and cautery was used in 24%, cryotherapy in 8%, and radiotherapy in 8%. On average, one in four tumours were referred to other specialists for treatment (range 0-70%). Very few patients (2%) were referred to a combined dermatology/radiotherapy/plastic surgery clinic, calling into question its value and availability. There was considerable variation in practices between dermatologists, demonstrating a clear need for individual, local audit of the management of this common dermatological problem. The data collected in this study form a suitable measure with which local performance may be compared.
Regulatory T cells hasten infant AIDS
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

HIV infection tends to develop into AIDS more quickly in infants than in adults. A study by Hartigan-O'Conner et al. (page 2679) now suggests that more potent infant regulatory T (T reg) cells are to blame.






Figure 1

Infants (black lines) have more powerful T reg cells that suppress SIV-fighting CD4+ T cells.




T reg cells cool down virus-induced immune responses by suppressing activated T cells. It has been suggested that too much suppression allows HIV to get the upper hand. Others, however, have suggested that activated T cell suppression by T reg cells prevents inflammatory T cell cytokines from damaging tissues and thus enhancing disease.

Hartigan-O'Conner and colleagues now show that healthy infant monkeys have more—and more potent—T reg cells than do adult monkeys. When monkeys were infected with SIV—the primate version of HIV—most of the infants rapidly developed AIDS. Their T reg cells suppressed anti-SIV T cell functions, whereas the adult T reg cells did not.

Humans also have more T reg cells during infancy. The authors suspect that, like primate T reg cells, the potency of human T reg cells might also decrease with age. Determining why T reg cell numbers decrease with age and why aging T reg cells lose their steam is the next step.