tbuckley/cabot-search huggingface dataset:
Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients
Authors: T Umemura
Journal: Gut (2006)

Autoimmune pancreatitis is characterised by irregular narrowing of the main pancreatic duct, swelling of the pancreas, histological evidence of lymphoplasmacytic inflammation, and high serum immunoglobulin G4 (IgG4) concentration.1–4 Although the human leucocyte antigen DRB1\*0405-DQB1\*0401 haplotype has been associated with autoimmune pancreatitis,5 the role of genetic factors has not yet been fully defined. A new family of genes called Fc receptor-like genes ( FCRL s), which have high structural homology with classical Fcγ receptor genes, has recently been identified.6,7 FCRL3 polymorphisms have been shown to be associated with various autoimmune diseases, such as rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus, in Japanese populations.8,9 These polymorphisms alter the binding affinity of nuclear factor κB and regulate FCRL3 expression. FCRL3 expression on B cells has been observed in significant amounts and …
A1.14 Characterisation and activation of dendritic cell subsets within the inflammed synovium of rheumatoid arthritis patients
Authors: M Canavan, M O’Rourke, C Orr, DJ Veale, U Fearon
Journal: Annals of the Rheumatic Diseases (2015)

<h3><b>Introduction</b></h3> Dendritic cells (DC) are a heterogeneous population of professional antigen presenting cells. Myeloid and plasmacytoid DC represent the two major DC subsets and can be distinguished based on their morphology, function and expression of surface markers. In this study we compared the percentage and maturation status of myeloid versus plasmacytoid DC at the site of inflammation in RA compared to systemic circulation. <h3>Methods</h3> RA synovial tissue biopsies obtained at arthroscopy were digested using the GentleMACs system. The RA synovial cells along with synovial fluid mononuclear cells and whole blood were phenotyped for myeloid DC (CD11c, HLADR, CD141 and CD1c) plasmacytoid DC (CD123, HLADR) activation markers (CD80, CD83 and CD40) and intracellular cytokines (IL-10) using multicolour flow cytometry. To assess the effect of the synovial microenvironment on DC maturation, RA synovial tissue explants were cultured for 24 h allowing spontaneous secretion of pro-inflammatory mediators into the medium (conditioned media). Monocyte derived DC (MoDC) were then cultured in the presence of RA explant conditioned media and expression of DC maturation markers was analysed by flow cytometry. <h3>Results</h3> A significant decrease in circulating CD11c mDC in RA peripheral blood compared to age matched HC was demonstrated (p &lt; 0.05). The expression of CD40 on pDC in RA patients was significantly increased compared to HC (p &lt; 0.001). CD40 and CD80 on mDC was significantly increased in synovial tissue and synovial fluid compared to that of matched peripheral blood (all p &lt; 0.05). MoDC cultured in the presence of RA explant conditioned media had an increased percentage of CD83 positive cells, with a significant increase in CD80 expression compared to basal control medium (p &lt; 0.05). Explant conditioned media also induced IL-10 production in MoDC as demonstrated by an increase in the percentage of intracellular IL-10 positive CD11c cells. <h3>Conclusion</h3> DC have a more mature phenotype in the synovial tissue compared to that in synovial fluid or peripheral blood. Given that there are also lower circulating levels of DC in RA patients compared to controls and that RA explant media can activate MoDC, our data suggests that DC are recruited to the joint and this unique inflammatory microenvironment induces a program of DC maturation and activation.
Tamoxifen reduces breast cancer by a third in high risk women
Authors: S. Mayor
Journal: BMJ (2002)

Tamoxifen reduces the risk of breast cancer by a third over four years in healthy women at high risk of developing the disease, a major international study has shown.

But the investigators consider that the increased risk of thromboembolism and endometrial cancers from the drug means that longer term follow up is needed before a clear recommendation can be made on its use in primary breast cancer prevention.

Results …
AT <sub>1</sub> and AT <sub>2</sub> Angiotensin Receptor Gene Expression in Human Heart Failure
Authors: Guy A. Haywood, Lars Gullestad, Tomohiro Katsuya, Howard G. Hutchinson, Richard E. Pratt, Masatsugu Horiuchi, Michael B. Fowler
Journal: Circulation (1997)

The availability of selective antagonists for angiotensin II receptors has focused interest on the gene expression of angiotensin II-receptor subtypes in the human heart.We analyzed expression of the AT1 and AT2 subtypes of the angiotensin II receptor in ventricular myocardium taken from 9 donor hearts before implantation and from 12 patients with heart failure (6 with dilated cardiomyopathy and 6 with ischemic heart disease). Competitive reverse transcription-polymerase chain reaction with synthetic RNA internal standards was used to detect mRNA for both subtypes and to quantify relative differences in levels between failing and non-failing ventricular myocardium. AT1- and AT2-receptor mRNA could be detected in all samples. AT1-receptor gene expression was 2.5-fold greater in nonfailing hearts than in patients with failing hearts (P = .015). There was no significant difference in AT2-receptor mRNA expression in failing and nonfailing hearts.The level of expression of the angiotensin AT1 receptor appears to decrease in the failing human ventricle whereas the level of AT2 expression is unaffected. These changes parallel the changes found in human ventricular myocardium at the receptor level, suggesting that the changes in receptor level may result from changes in gene expression or mRNA stability.
General Physiology: Motor and Psychomotor Functions
Authors: Sidney Ochs
Journal: JAMA (1971)

Professor Monnier has undertaken an heroic assignment, to deal with the whole of the nervous system in four large volumes. In this, the second volume, the groundwork for motor function is laid with a discussion of nerve conduction, neuromuscular transmission, and the simpler reflexes. In these preliminary matters the author is least successful. The space alloted is too short and the development complicated by the retention of superseded concepts, eg, Lapique's theory of isochronicity, Pfluger's laws, the theory of electrical transmission in the spinal cord. The author's forte is in dealing with the higher reflexes. This central theme is introduced in chapter 10, where the concept of integration is advanced as a basic purposeful plan of the nervous system. This is developed in the remaining chapters dealing with defensive reflexes (flexion reflex), grasping, postural functions, the vestibular system, the relation of cerebellar and reticular formation control to posture, locomotion, equilibration,
Rilonacept for Colchicine-Resistant or -Intolerant Familial Mediterranean Fever
Authors: Philip J. Hashkes, Steven J. Spalding, Edward H. Giannini, Bin Huang, Anne Johnson, Grace Park, Karyl S. Barron, Michael H. Weisman, Noune Pashinian, Andreas O. Reiff, Jonathan Samuels, Dowain A. Wright, Daniel L. Kastner, Daniel J. Lovell
Journal: Annals of Internal Medicine (2012)

Chinese translation This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF. Objective: To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF. Design: Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907). Setting: 6 U.S. sites. Patients: Patients with FMF aged 4 years or older with 1 or more attacks per month. Intervention: One of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo. Measurements: Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo. Results: 8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept–placebo attack risk ratio was 0.45 (SD, 0.13) (equal-tail 95% credible interval, 0.26 to 0.77). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, −1.74 [95% CI, −3.4 to −0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [−0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of −4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen in other adverse events. Limitation: Small sample size, heterogeneity of FMF mutations, age, and participant indication (colchicine resistance or intolerance) were study limitations. Conclusion: Rilonacept reduces the frequency of FMF attacks and seems to be a treatment option for patients with colchicine-resistant or -intolerant FMF. Primary Funding Source: U.S. Food and Drug Administration, Office of Orphan Products Development.
Rare occurrence of CD30+ circulating cells in patients with cutaneous CD30+ anaplastic large cell lymphoma: a study of nine patients
Authors: O. Dereure, P. Portales, M. Balavoine, P. Corbeau, B. Guillot, J. Clot, J-J. Guilhou
Journal: British Journal of Dermatology (2003)

The presence of a significant percentage of circulating atypical lymphocytes in peripheral blood has already been demonstrated in systemic CD30+ anaplastic large cell lymphoma (ALCL), which implies that a leukaemic component may be present in this subset of lymphomas. However, no similar data are available for the cutaneous counterpart of this particular lymphoproliferation.To assess the presence of atypical cells, CD30+ lymphocytes and of a dominant T-cell clone in peripheral blood in a series of patients with cutaneous CD30+ ALCL.Nine patients with either primary (four) or secondary (five) cutaneous CD4+ CD30+ ALCL were selected. The percentage of CD30+ CD4+ lymphocytes among peripheral blood mononuclear cells (PBMC) was determined by flow cytometry and the presence of a dominant circulating T-cell clone was assessed by polymerase chain reaction targeting the T-cell receptor gamma chain. A control group composed of apparently healthy individuals was similarly studied at the same time.The mean percentage of CD30+ cells in PBMC was slightly higher in patients than in controls (3.9% vs. 2.7%) but the difference was not statistically significant. Only two patients displayed more than 5% CD30+ cells, both of whom had a minor tumour burden. A dominant circulating T-cell clone was detected in only three cases, including these two latter patients.The occurrence of a significant percentage of CD30+ CD4+ circulating cells is rare in active cutaneous CD30+ ALCL, either primary or secondary. This percentage is not related to the apparent skin tumour burden but a significant figure appeared to be correlated with the detection of a dominant T-cell clone in peripheral blood. Overall, these data show that, unlike mycosis fungoides, peripheral blood involvement seems infrequent in cutaneous CD30+ ALCL. The hypothesis that a high percentage of CD30+ circulating cells might be related to the presence of a cryptic systemic disease cannot be ruled out.
Human Endogenous Retrovirus K Triggers an Antigen-Specific Immune Response in Breast Cancer Patients
Authors: Feng Wang-Johanning, Laszlo Radvanyi, Kiera Rycaj, Joshua B. Plummer, Peisha Yan, K. Jagannadha Sastry, Chandrika J. Piyathilake, Kelly K. Hunt, Gary L. Johanning
Journal: Cancer Research (2008)

Recent evidence indicates that human cancer cells reactivate the expression of latent human endogenous retroviral (HERV) proteins. However, the extent to which cancer patients mount de novo immune responses against expressed HERV elements is unclear. In this study, we determined the extent of HERV-K env expression in human breast cancer (BC) and whether both humoral and cell-mediated immunity against HERV-K can be found in BC patients. We found HERV-K env protein expression in 88% of BC (n = 119) but not in normal breast (n = 76) tissues. ELISA screening assays detected significant titers of anti-HERV-K env IgG in a large proportion of BC patients. T-cell responses against HERV-K were also detected in peripheral blood mononuclear cells (PBMC) from BC patients stimulated with autologous dendritic cells pulsed with HERV-K env SU antigens. These responses included induction of T-cell proliferation (P = 0.0043), IFN-gamma production measured by enzyme-linked immunospot (P < 0.0001), and multiplex cytokine secretion (P = 0.0033). Multiplex cytokine analysis found a T-helper 1 cytokine response, including interleukin (IL)-2 (P = 0.0109), IL-6 (P = 0.0396), IL-8 (P = 0.0169), and IP-10 (P = 0.0045) secretion during in vitro stimulation of BC PBMC with HERV-K antigen. We also found HERV-K-specific CTLs that were capable of lysing target cells expressing HERV-K env protein in BC patients but not in normal female controls without cancer. These findings suggest that retroviral gene products are capable of acting as tumor-associated antigens activating both T-cell and B-cell responses in BC patients.
Personalised care for patients with type 2 diabetes reduces complications, study finds
Authors: L. Anekwe
Journal: BMJ (2013)

People with type 2 diabetes who work with their doctors to set individual goals for their treatment have a reduced risk of developing complications, according to a study that followed patients for 19 years.

Researchers from Denmark followed up patients who had taken part in the Diabetes Care In General Practice study—a randomised controlled trial that assessed the effect of six years of structured personal care compared with routine care.1 This study involved 474 general practitioners (GPs) who …
Obesity-Diabetes and Anorexigenics
Authors: S. K. Fineberg
Journal: JAMA (1961)

Previous observations on 62 obese diabetic patients showed that phenmetrazine hydrochloride significantly reduced appetite and weight. In the present study 30 obese diabetic patients were divided into two groups. Each patient received 25 mg. per day of either phenmetrazine hydrochloride or diethylpropion under "double-blind" conditions. Group A (14 patients) lost, on the average, 6.71 lb. (3.05 kg.) during an initial six-week phenmetrazine period and 1.37 lb. (0.62 kg.) during the subsequent six-week diethylpropion period. Group B (16 patients) lost 2.77 lb. (1.26 kg.) during their initial six weeks of taking diethylpropion and 3.44 lb. (1.56 kg.) during the subsequent six-week phenmetrazine period. Both drugs were significantly anorexigenic; but in the dosages used, phenmetrazine caused both greater weight-loss and a higher incidence of side-effects.
RECENT ADVANCES IN THE MEDICAL TREATMENT OF CIRRHOSIS OF THE LIVER
Authors: Sidney A. Portis
Journal: JAMA (1952)

The incidence of cirrhosis of the liver is increasing. Whereas previously it was seen mostly with alcoholism or malnutrition or as a complication of cholecystitis and cholelithiasis, physicians today are confronted with additional causative factors. The widespread epidemic hepatitis of World War II produced a sporadic inoculation of persons hitherto never exposed to the virus of infectious hepatitis. The etiological relationship of acute infectious hepatitis to cirrhosis of the liver is favored by most authors. 1   Sulfonamides and other hepatotoxic agents have taken their toll of the liver. Aureomycin has been rather extensively used in the treatment of acute and chronic hepatitis. Recently Lepper 2 reported that, among 14 patients given large doses of aureomycin for serious infections, both by mouth and intravenously, 7 showed clinical evidence of liver dysfunction. Furthermore, necropsy in five and biopsy in one of these cases showed pathological changes in the liver cells; however, the
Lymphocytotoxins in Leukaemia
Authors: A. Dickson
Journal: BMJ (1972)

Fifteen out of 51 patients with leukaemia have produced a lymphocytotoxin in their serum which reacts with their own and a high percentage of all other lymphocytes. This is probably a protein, but not an antibody. It has been detected only before or early during cytotoxic treatment, or during a relapse. It is postulated that the lymphocytotoxin is a specific protein produced by the leukaemic cells, which may facilitate their spread in the body.
The effect of cardiac tamponade on coronary haemodynamics in the awake dog
Authors: J. M. M. JARMAKANI, P. A. MCHALE, J. C. GREENFIELD
Journal: Cardiovascular Research (1975)

Journal Article The effect of cardiac tamponade on coronary haemodynamics in the awake dog Get access JAY M. M. JARMAKANI, JAY M. M. JARMAKANI 2 From the Departments of Pediatrics, Physiology, and Medicine (Division of Cardiology), Veterans Administration Hospital, Durham, North Carolina 27705 and Duke University Medical Center, Durham, North Carolina 27710, USA 2Present address: Department of Pediatrics, UCLA Medical Center, Los Angeles, California 90024, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar PHILIP A. MCHALE, PHILIP A. MCHALE From the Departments of Pediatrics, Physiology, and Medicine (Division of Cardiology), Veterans Administration Hospital, Durham, North Carolina 27705 and Duke University Medical Center, Durham, North Carolina 27710, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar JOSEPH C. GREENFIELD, JR JOSEPH C. GREENFIELD, JR From the Departments of Pediatrics, Physiology, and Medicine (Division of Cardiology), Veterans Administration Hospital, Durham, North Carolina 27705 and Duke University Medical Center, Durham, North Carolina 27710, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 9, Issue 1, January 1975, Pages 112–117, https://doi.org/10.1093/cvr/9.1.112 Published: 01 January 1975
CaMKII γ, a critical regulator of CML stem/progenitor cells, is a target of the natural product berbamine
Authors: Ying Gu, Ting Chen, Zhipeng Meng, Yichao Gan, Xiaohua Xu, Guiyu Lou, Hongzhi Li, Xiaoxian Gan, Hong Zhou, Jinfen Tang, Genbo Xu, Liansheng Huang, Xiaohong Zhang, Yongming Fang, Kai Wang, Shu Zheng, Wendong Huang, Rongzhen Xu
Journal: Blood (2012)
The Cost-effectiveness of Voluntary Counseling and Testing of Hospital Inpatients for HIV Infection
Authors: Peter Lurie, Andrew L. Avins, Kathryn A. Phillips, James G. Kahn, Robert A. Lowe, Daniel Ciccarone
Journal: JAMA (1994)

To evaluate the cost-effectiveness of voluntary counseling and testing of US hospital inpatients for the human immunodeficiency virus (HIV).Data for entry into the model were derived from a review of the literature, consultation with experts, and consensus of the authors.We rated our confidence in these probabilities and costs by grading the data inputs using methods adapted from those of the US Preventive Services Task Force.Decision analysis models were developed to evaluate two outcomes: (1) cost per health care worker (HCW) HIV infection averted if measures are taken by the HCW to reduce his or her risk of acquiring HIV; and (2) cost per inpatient HIV infection detected. Sensitivity analyses were also conducted. Using baseline input values, testing to avert HCW infection may prevent 3.6 HIV infections per year at a total program cost of $2.7 billion, or a cost of $753 million per infection averted. At baseline assumptions (seroprevalence = 1%), testing to detect inpatient HIV infection would cost $16,104 per year per infection detected. Cost-effectiveness at baseline drops to $8353 per HIV infection detected if the seroprevalence is 10%. If testing is limited to hospitals with inpatient seroprevalences of at least 1%, approximately 5400 persons per year will be falsely labeled HIV-positive.This analysis provides no justification for testing inpatients to prevent HIV infection of HCWs. Screening inpatients to detect HIV infection may be justified at seroprevalences exceeding 1%, but issues of medical or social discrimination, false-positive results, informed consent, and logistics must be resolved first.
Diffuse myelitis associated with rubella vaccination.
Authors: P O Behan
Journal: BMJ (1977)

mortality.It would simply mean that the cause of death would be different.Enabling people to live longer-perhaps for 20 years after retirement-would create economic problems no less great than at present.There would perhaps be the com- pensation that more and more of the un- employed could be used in looking after the aged.Or will you be proposing what the Archbishop of Canterbury hinted at when financial resources really dry up ?S ELLISON London NW6A cautionary tale SIR,-'Tis with a sense of grievous shock That one observed great Stephen Lock To perpetrate the awful sin Of leaving an unchecked reference in An article that bears his name.'This blot on editorial fame Though "For Debate" is clear to see At least to Belloc and to me: It was not Lundy's noble dad Who did advise the tearful lad It was his grandpapa the Duke -Sir, what a liberty you took!
Epstein-Barr virus associated oesophageal ulcers in AIDS.
Authors: V S Kitchen, M Helbert, N D Francis, R P Logan, F A Lewis, A W Boylston, A J Pinching, J R Harris
Journal: Gut (1990)

Epstein-Barr virus (EBV) associated ulceration has not previously been included in the differential diagnosis of oesophageal ulcers in AIDS. We report five cases of oesophageal ulceration in homosexual men with advanced human immunodeficiency virus infection in whom this was considered to be the most likely cause. DNA in situ hybridisation studies showed EBV in biopsy material from three of four patients with oesophageal ulcers and in none of three controls. Of other viruses studied, only human papillomavirus was present, and this was found in both patients and control subjects. These findings support the hypothesis that EBV is an aetiological factor in some cases of AIDS-associated oesophageal ulceration.
Treatment of Infective Endocarditis
Authors: Jerry D. Smilack
Journal: JAMA (1982)

Endocarditis possesses a mystique few other diseases in clinical medicine have. I recall a time—not very many years ago—during my residency training when a practicing internist told me of a patient with bacterial endocarditis for whom he was caring in his community hospital. I thought patients with such fascinating conditions were shunted to gargantuan medical centers in the metropolis! Of course, my naiveté disappeared when I entered the "real world" of medical practice and learned how commonly questions about endocarditis arise. Although the disease has fascinated physicians for years, its changing nature requires periodic reassessment. There has been a profound alteration in the type of patient in whom the infection develops, from the young person with rheumatic valvular disease to the elderly with degenerative or calcific valvular changes, patients with mitral valve prolapse, intravenous drug users, persons with prosthetic valves—groups presenting problems not even envisioned in the days of Osier.