tbuckley/cabot-search huggingface dataset:
Peripheral joint ankylosis in the spontaneous model of arthritis in DBA/1 mice is associated with a locus on chromosome 3 that contains the bone morphogenetic protein type 1b receptor
Authors: S Carter, I Derese, K Braem, A M Valdes, F P Luyten, R J Lories
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Progression of ankylosis in patients with ankylosing spondylitis is highly variable, suggesting that ankylosis is at least partially due to genetic factors. The authors used a murine ankylosing enthesitis mouse model (DBA/1) to search for disease-associated genes and limb bud pellet culture to examine differences in cartilage and bone formation between DBA/1 and BALB/c mice. <h3>Materials and methods</h3> Male DBA/1 were crossed with female BALB/c mice. At 26 weeks, histomorphology was examined in male F2 mice from different litters. 159 markers with sequence-length polymorphisms on the autosomes were selected, with a median marker spacing of 6.9 cM. 162 F2 male mice were studied. Genes in regions of interests were linked to skeletal development pathways with the Gene Ontology database. Association was evaluated by χ2 tests with a False Discovery Rate (FDR) algorithm. Limb bud pellet cultures were prepared from mesenchymal cells isolated from the forelimbs of 11.5 dpc BALB/c and DBA/1 embryos. High-density pellets were cultured in DMEM-F12 or GDF5 for 7 days. RNA was extracted and chondrogenic and osteogenic markers were assessed by qPCR. <h3>Results</h3> Incidence of ankylosing enthesitis was lower in the F2 generation as compared to wild-type DBA/1 males (42% vs 72%; p&lt;0.0001). When applying the FDR algorithm for 159 markers, associations with <i>D3MIT199</i> and <i>D3MIT160</i> were significant (p&lt;0.016). Adjacent markers were additionally genotyped. In the associated region between markers <i>D3MIT42</i> and <i>D3MIT129</i>, 162 genes were found among which <i>Bmpr1b, Cxxc4, Lef1, Papss1, Pitx2</i>, and <i>Ube2d3</i>. Only BMP receptor type 1b (<i>Bmpr1b</i>) was specifically upregulated in mice with spontaneous arthritis as demonstrated by qPCR. Additionally, Bmpr1b ligand, GDF5, induces differential expression of osteogenic genes in cultures from BALB/c mice as compared to DBA/1 mice. Osterix (OSX), osteocalcin (OC) and bone siaoloprotein (BSP) are all significantly upregulated in BALB/c cultures after 5 days in the presence of GDF5. <h3>Conclusions</h3> Using F2 mouse genetics in the analysis of joint ankylosis, The authors identified a locus on chromosome 3 that shows association to disease. Within this locus several genes may play a role in ankylosis, however, our functional data suggests that Bmpr1b is involved. The response to GDF5 in limb bud cultures highlights that differences exist in the GDF5-Bmpr1b pathway in BALB/c and disease-susceptible DBA/1 mice, further corroborating an essential role for BMPs in human and murine ankylosis.
Internucleosomal DNA fragmentation during phorbol ester-induced monocytic differentiation and G0/G1 arrest.
Authors: H Gunji, R Hass, D Kufe
Journal: Journal of Clinical Investigation (1992)

The treatment of human myeloid leukemia cell lines with phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is associated with loss of proliferative capacity and induction of monocytic differentiation. The present results demonstrate that treatment of asynchronous human U-937 leukemia cells with 10 nM TPA is also associated with oligonucleosomal DNA cleavage. This pattern of DNA fragmentation, which is observed in programmed cell death, was detectable in populations of TPA-treated cells that had entered a nonproliferative G0/G1 phase. Similar findings were obtained after TPA treatment of a synchronous population of G1 cells. These cells progressed through S and G2/M phases before undergoing internucleosomal DNA cleavage during G0/G1 arrest. These G0/G1 cells displayed characteristics of monocytic differentiation, including down-regulation of c-myc expression and induction of c-fms transcripts. DNA fragmentation was also studied in cells treated with 5 nM TPA for 48 h and then monitored in drug-free long-term culture. Endonucleolytic cleavage was similarly observed in the differentiated G0/G1 population. However, longer periods of culture were associated with a decrease in DNA fragmentation to undetectable levels. This effect was followed by retrodifferentiation and reentry of cells into cycle. Taken together, these findings demonstrate that internucleosomal DNA fragmentation occurs during induction of monocytic differentiation, and that both of these events are detectable in G0/G1 cells.
Urine Composition in Type 2 Diabetes
Authors: Mary Ann Cameron, Naim M. Maalouf, Beverley Adams-Huet, Orson W. Moe, Khashayar Sakhaee
Journal: Journal of the American Society of Nephrology (2006)

Type 2 diabetes is a risk factor for nephrolithiasis in general and has been associated with uric acid stones in particular. The purpose of this study was to identify the metabolic features that place patients with type 2 diabetes at increased risk for uric acid nephrolithiasis. Three groups of individuals were recruited for this outpatient study: Patients who have type 2 diabetes and are not stone formers (n = 24), patients who do not have diabetes and are uric acid stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Twenty-four-hour urine volume and total uric acid did not differ among the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH than NV. Urine pH inversely correlated with both body weight and 24-h urine sulfate in all groups. Urine pH remained significantly lower in patients with type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate (P < 0.01). For a given urine sulfate, urine net acid excretion tended to be higher in patients with type 2 diabetes versus NV. With increasing urine sulfate, NV and patients with type 2 diabetes had a similar rise in urine ammonium, whereas in UASF, ammonium excretion remained unchanged. The main risk factor for uric acid nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body mass and increased acid intake can contribute to but cannot entirely account for the lower urine pH in patients with type 2 diabetes.
EXPLORATION AND DECAPSULATION OF THE OTHER KIDNEY BEFORE COMPLETING A NEPHRECTOMY.
Authors: GEORGE M. EDEBOHLS
Journal: JAMA (1907)

In recent years an enormous amount of painstaking scientific investigation and persistent, praiseworthy effort have been expended on the part of such masters as Koranyi, Kümmell, Casper, Israel, Rovsing, their assistants, and many others, with a view to finding and elaborating a reliable method of determining the functional activity or possibilities of each kidney separately, or of both kidneys combined, in advance of a contemplated or possible nephrectomy. The result of all this investigation and effort has been to add one after another to the already long and still growing list of so-called functional tests. Yet despite the fact that every recent writer on the subject, with or without personal experience in the matter, feels himself called on to discuss at greater or less length all and sundry of the various functional tests of which he may have heard or read, it can not be said that anything even approaching
Ileal cancer and erosions in the small intestine revealed by capsule endoscopy
Authors: Y. Niwa, M. Nakamura, N. Omiya, A. Itoh, Y. Hirooka, H. Goto
Journal: Endoscopy (2007)

An 80-year-old man with persistent anemia was suspected to have a hemorrhagic lesion in the small intestine and he underwent investigation by capsule endoscopy. This examination revealed several erosions and reddened lesions in the pelvic small intestine (Figure [1]). On 17 May 2005 he was started on a prostaglandin inducer, rebamipide, at a daily dose of 300 mg, and although the iron preparation he was on was stopped, there was no decrease in his hemoglobin level. On 1 July a second capsule endoscopy examination revealed marked improvement - the erosions and reddened lesions in the small intestine had resolved (Figure [2]). The second capsule endoscopy allowed observation nearly as far as the terminal ileum, where a protruding lesion was detected (Figure [3]). Double-balloon endoscopy revealed a red type Ip polyp, about 30 cm proximal to the ileocecal valve (Figure [4]). In addition, there was an advanced cancer resembling a type IIc early cancer in the ascending colon (Figure [5]).
Apoptotic cells attenuate fulminant hepatitis by priming Kupffer cells to produce interleukin-10 through membrane-bound TGF-β
Authors: Minggang Zhang, Sheng Xu, Yanmei Han, Xuetao Cao
Journal: Hepatology (2010)

The liver, a unique tolerogenic organ, is regarded as the site to trap and destroy aging erythrocytes and activated T cells. However, to date, the mechanisms for why the liver is tolerogenic and whether liver Kupffer cells (KC) are critical phagocytes for apoptotic cells (AC) contributing to the liver immunosuppression remain unclear. Here we report that KC is the main phagocyte for AC in the liver. Contact of AC inhibits proinflammatory cytokine but enhances anti-inflammatory cytokine production of KC in response to lipopolysaccharide (LPS) stimulation. Membrane-bound transforming growth factor (TGF)-β on AC is responsible for the increased production of interleukin (IL)-10 in KC through extracellular signal-regulated kinase (ERK) activation via the Smad3 pathway. Importantly, KC-derived IL-10 is critical for AC infusion-mediated protection of endotoxin-induced fulminant hepatitis through suppression of tumor necrosis factor (TNF)-α and nitric oxide (NO) production from KC and consequently attenuation of KC-mediated cytolysis of hepatocytes. Conclusion: AC can be preferentially phagocytosed by KC in the liver, leading to attenuation of fulminant hepatitis through IL-10-mediated suppression of KC-derived inflammatory TNF-α and NO production. These findings demonstrate that priming of KC by AC may contribute to maintain liver immunosuppression, providing a new mechanistic explanation for how immune homeostasis is maintained in the liver. (Hepatology 2011.)
The Medical and Psychosocial Impact of Comprehensive Care on Adolescent Pregnancy and Parenthood
Authors: Arthur B. Elster
Journal: JAMA (1987)

To assess the medical and psychosocial effects of services provided by a comprehensive adolescent pregnancy and parenthood program, 125 adolescents who received care from a comprehensive program were compared with 135 adolescents who received care from community health providers. Few differences were found in pregnancy outcome measures. At 12 and 26 months after delivery, however, the intervention group scored significantly better on composite measures encompassing medical, psychosocial, and parenting events than did the comparison group, even after accounting for possible confounding factors. This suggests that comprehensive care has little effect on pregnancy outcomes for those adolescents who are already receiving prenatal and nutritional services, but does have a significant effect on events occurring during the first and second postpartum years. (<i>JAMA</i>1987;258:1187-1192)
Diclofenac-associated hepatotoxicity: Analysis of 180 cases reported to the food and drug administration as adverse reactions
Authors: Alpha T. Banks, Hyman J. Zimmerman, Kamal G. Ishak, John G. Harter
Journal: Hepatology (1995)

Diclofenac is a nonsteroidal anti-inflammatory drug approved in the United States in 1988 for the treatment of patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. To characterize the clinical, biochemical, and histological features and possible mechanisms of hepatic injury associated with its use, a retrospective analysis was undertaken of 180 patients whose cases were reported to the Food and Drug Administration from November 1988 through June 1991, as having had possible adverse reactions to diclofenac. Of the reported 180 cases, 79% were female, 71% were 60 years of age or older, and 77% had osteoarthritis. Sixty-seven percent of the cases were detected by symptoms and the remainder by abnormal laboratory tests. Seventy-five percent of the symptomatic patients (90 of 120) were jaundiced. Seven of the 90 icteric patients died. The biochemical pattern of injury was hepatocellular or mixed hepatocellular in 66% of cases. Only 8% had a pattern of cholestatic injury. The remainder, with modestly increased values of both transaminases and alkaline phosphatase, were considered "indeterminate," i.e., either mild hepatocellular or anicteric "cholestatic" injury. Sections of liver from 21 cases were available for study. Hepatic injury was apparent by 1 month after starting the drug in 24%, by 3 months in 63%, and by 6 months in 85% of cases. The latent period in 12% was 6 to 12 months, whereas in 3% it was greater than 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Vaccines for Enterovirus 71
Authors: Anita Slomski
Journal: JAMA (2014)

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Human Maternal and Fetal Insulin Response to Arginine
Authors: Katherine C. King, J. Butt, K. Raivio, Niels Räihä, J. Roux, K. Teramo, K. Yamaguchi, R. Schwartz
Journal: New England Journal of Medicine (1971)

Maternal and fetal insulin response to arginine was examined by infusion of arginine to pregnant women during delivery of their fetuses or to newborn infants directly. Nonpregnant adult subjects were studied as controls. A positive correlation between plasma immunoreactive insulin concentration and plasma arginine concentration was found in the control subjects. The pregnant women at 13 to 18 weeks' gestation had an attenuated insulin response to arginine, whereas the responses of the women during labor and delivery at term were more variable. The fetuses in utero had no significant plasma insulin rise to maternal infused arginine. The newborn infant, however, had attenuated though significant insulin response to intravenous arginine infusion.
Abstract LB-54: Identification of a RAF inhibitory auto-phosphorylation site.
Authors: Matthew Holderfield, Hanne Merritt, Julie Lin, Zenhai Gao, Darrin Stuart, Frank McCormick
Journal: Cancer Research (2013)

Abstract Preclinical studies have demonstrated that BRAF wild-type cancer cells are not only refractory but paradoxically activate the MAPK pathway when treated with RAF inhibitors. Potentially through a related mechanism, multiple point mutations in the activation loop and Phosphate binding loop (P. loop) domains of BRAF have been characterized in human cancers, which often render BRAF catalytically impaired, yet stimulate phosphorylation of downstream targets in cells. However, the underlying biochemistry causing these phenomena has yet to be fully understood. In this study we investigate the biochemical mechanism of wild-type RAF activation in response to RAF inhibitor treatment and identify a novel auto-phosphorylation site within the well conserved BRAF/CRAF P. loop. Disruption of the auto-phosphorylation, either through pharmacologic or genetic alterations, results in activation of the MAPK pathway. This work offers new insight into RAF biochemistry by uncovering a previously unrecognized regulatory mechanism of RAF kinases that is bypassed by the BRAF oncoproteins. Citation Format: Matthew Holderfield, Hanne Merritt, Julie Lin, Zenhai Gao, Darrin Stuart, Frank McCormick. Identification of a RAF inhibitory auto-phosphorylation site. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-54. doi:10.1158/1538-7445.AM2013-LB-54
Reply to Tommaso Cai and Riccardo Bartoletti's Letter to the Editor re: Reinhold Zimmermann, Alin Cumpanas, Florin Miclea, Günter Janetschek. Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome in Males: A Randomised, Double-Blind, Placebo-Controlled Study. Eur Urol 2009;56:418–24
Authors: Reinhold P. Zimmermann, Günther Janetschek
Journal: European Urology (2009)
SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma
Authors: Jean-Pierre Bayley, Henricus PM Kunst, Alberto Cascon, Maria Lourdes Sampietro, José Gaal, Esther Korpershoek, Adolfo Hinojar-Gutierrez, Henri JLM Timmers, Lies H Hoefsloot, Mario A Hermsen, Carlos Suárez, A Karim Hussain, Annette HJT Vriends, Frederik J Hes, Jeroen C Jansen, Carli M Tops, Eleonora P Corssmit, Peter de Knijff, Jacques WM Lenders, Cor WRJ Cremers, Peter Devilee, Winand NM Dinjens, Ronald R de Krijger, Mercedes Robledo
Journal: The Lancet Oncology (2010)
The Care of Patients With AIDS: Don't Ignore the Family Practitioner
Authors: Alan P. Zelicoff
Journal: JAMA (1989)

<h3>To the Editor. —</h3> Among the many well-known problems summarized by Dr Cotton,<sup>1</sup>none is of greater concern than finding adequate numbers of well-trained physicians and other providers to care for the ever increasing population of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Dr Cotton suggests that the general internist is the most appropriate specialist to direct the care of the patient with AIDS. While this assertion may or may not be true, it is likely to occur by default, as family practitioners will doubtless hide behind their professed inadequacy to treat AIDS and subspecialists will decline by virtue of their "focused, hospital-based" training. Yet, a simple calculation demonstrates that Dr Cotton's prescription falls far short of the mark unless there is a clear commitment to adequate funding for AIDS care. Let us make the following assumptions: (1) There are likely to be about a million patients
Voxelwise Correlational Analyses of White Matter Integrity in Multiple Cognitive Domains in Schizophrenia
Authors: Kelvin O. Lim, Babak A. Ardekani, Jay Nierenberg, Pamela D. Butler, Daniel C. Javitt, Matthew J. Hoptman
Journal: American Journal of Psychiatry (2006)

Patients with schizophrenia show deficits in several neurocognitive domains. However, the relationship between white matter integrity and performance in these domains is poorly understood. The authors conducted neurocognitive testing and diffusion tensor imaging in 25 patients with schizophrenia. Performance was examined for tests of verbal declarative memory, attention, and executive function. Relationships between fractional anisotropy and cognitive performance were examined by using voxelwise correlational analyses. In each case, better performance on these tasks was associated with higher levels of fractional anisotropy in task-relevant regions.
Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis
Authors: H A Isomaki, T Hakulinen, U Joutsenlahti
Journal: Annals of the Rheumatic Diseases (1982)

The incidence of malignant neoplasms among 11 483 male and 34 618 female individuals with rheumatoid arthritis was studied using two separate nationwide data registers covering the whole Finnish population: the Social Insurance Institution9s Population Data Register, which includes information on medication for certain chronic diseases, and the Finnish Cancer Registry, with data on all cancer patients diagnosed in Finland. The follow-up comprised a total of 213 911 person years. The total incidence of all malignant neoplasms was higher in males and on the level expected in females. The expected number of cases of leukemia, lymphomas, Hodgkin9s disease and myeloma in both sexes was 59·6 as compared with the 130 cases observed. This difference is statistically highly significant (p&lt;0·001). The incidence of cancer of the respiratory organs was higher in males, and the incidence of cancer of the rectum and stomach lower than expected in rheumatoid females.
A review of mentation in REM and NREM sleep: “Covert” REM sleep as a possible reconciliation of two opposing models
Authors: Tore A. Nielsen
Journal: Behavioral and Brain Sciences (2000)

Numerous studies have replicated the finding of mentation in both rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. However, two different theoretical models have been proposed to account for this finding: (1) a one-generator model, in which mentation is generated by a single set of processes regardless of physiological differences between REM and NREM sleep; and (2) a two-generator model, in which qualitatively different generators produce cognitive activity in the two states. First, research is reviewed demonstrating conclusively that mentation can occur in NREM sleep; global estimates show an average mentation recall rate of about 50% from NREM sleep – a value that has increased substantially over the years. Second, nine different types of research on REM and NREM cognitive activity are examined for evidence supporting or refuting the two models. The evidence largely, but not completely, favors the two-generator model. Finally, in a preliminary attempt to reconcile the two models, an alternative model is proposed that assumes the existence of covert REM sleep processes during NREM sleep. Such covert activity may be responsible for much of the dreamlike cognitive activity occurring in NREM sleep.
Congenital Heart Disease in Relation to Maternal Use of Bendectin and Other Drugs in Early Pregnancy
Authors: Sally Zierler, Kenneth J. Rothman
Journal: New England Journal of Medicine (1985)

To clarify the association of Bendectin and other drugs used in early pregnancy with the occurrence of congenital heart disease, we interviewed 298 mothers of children with congenital heart disease and 738 mothers of healthy controls. Differential recall of drug use by mothers of affected children and mothers of controls was evaluated by comparison of information collected by interview with that recorded in the prenatal record. Data derived from maternal interviews were generally consistent with the record data. Reported Bendectin use was minimally associated with congenital heart disease (prevalence odds ratio, 1.1; 90 per cent confidence interval, 0.8 to 1.5). The data from this study were consistent with previously reported associations of other drugs with congenital heart disease. In particular, aspirin use in early pregnancy was associated with about a twofold increase in the frequency of defects in septation of the truncus arteriosus (prevalence odds ratio, 2.1; 90 per cent confidence interval, 1.1 to 3.9). (N Engl J Med 1985; 313:347–52.)