tbuckley/cabot-search huggingface dataset:
Intrauterine insemination: a systematic review on determinants of success
Authors: H. E. Duran
Journal: Human Reproduction Update (2002)

Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in infertility. Here, a systematic review of the literature was performed to examine the current status of clinical and laboratory methodologies used in IUI and the impact of female and male factors on pregnancy success. Emphasis was centred in questioning the following: (i) the value of IUI against timed intercourse; (ii) IUI application with or without controlled ovarian hyperstimulation; (iii) timing and frequency of IUI; and (iv) impact of various parameters (male/female) on the prediction of pregnancy outcome. The odds of multiple pregnancy occurrence and its risk factors, as well as the cost-effectiveness of IUI treatment compared with more complex assisted reproductive technologies are discussed. A computerized literature search was performed including Medline and the Cochrane library, as well as a crossover search from retrieved papers. It is concluded that although IUI is a successful contemporary treatment for appropriately selected cases of female and/or male infertility, further research is needed through well-designed studies to improve the methodologies currently utilized. Importantly, the clinical management of the infertile couple should be performed in an expedited manner taking into consideration the age of the woman, the presence of multifactorial infertility and cost-effectiveness of the available treatment alternatives.
Smoking Cessation and the Risk of Stroke in Middle-aged Men
Authors: S. Goya Wannamethee
Journal: JAMA (1995)

To examine the effects of giving up smoking, years since quitting smoking and the quantity of cigarettes smoked, and primary pipe or cigar smoking on the risk of stroke.A prospective study of cardiovascular disease and its risk factors in 7735 men aged 40 through 59 years drawn at random from the age-sex registers of one general practice in each of 24 British towns from 1978 through 1980 (the British Regional Heart Study).Incidence of fatal and nonfatal major stroke events (strokes) during an average follow-up period of 12.75 years.During the 12.75 years of follow-up, there were 167 major stroke events (43 fatal and 124 nonfatal) in the 7264 men with no recall of previous ischemic heart disease or stroke. After full adjustment for other risk factors, current smokers had a nearly fourfold relative risk (RR) of stroke compared with never smokers (RR, 3.7; 95% confidence interval [CI], 2.0 to 6.9). Ex-cigarette smokers showed lower risk than current smokers but showed excess risk compared with never smokers (RR, 1.7; 95% CI, 0.9 to 3.3; P = .11); those who switched to pipe or cigar smoking showed a significantly increased risk (RR, 3.3; 95% CI, 1.6 to 7.1) similar to that of current light smokers. Primary pipe or cigar smokers also showed increased risk (RR, 2.2; 95% CI, 0.6 to 8.0), but the number of subjects involved was small. The benefit of giving up smoking completely was seen within 5 years of quitting, with no further consistent decline in risk thereafter, but this was dependent on the amount of tobacco smoked. Light smokers (< 20 cigarettes/d) reverted to the risk level of those who had never smoked. Heavy smokers retained a more than twofold risk compared with never smokers (RR, 2.2; 95% CI, 1.1 to 4.3). The age-adjusted RR of stroke in those who quit smoking during the first 5 years of follow-up (recent quitters) was reduced compared with continuing smokers (RR, 1.8; 95% CI, 0.7 to 4.6 vs RR, 4.3; 95% CI, 2.1 to 8.8). The benefit of quitting smoking was observed in both normotensive and hypertensive men, but the absolute benefit was greater in hypertensive subjects.Smoking cessation is associated with a considerable and rapid benefit in decreasing the risk of stroke, particularly in light smokers (< 20 cigarettes/d); a complete loss of risk is not seen in heavy smokers. Switching to pipe or cigar smoking confers little benefit, emphasizing the need for complete cessation of smoking. The absolute benefit of quitting smoking on risk of stroke is most marked in hypertensive subjects.
Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis
Authors: Chunqing Guo, Fanlei Hu, Huanfa Yi, Zhitao Feng, Changzheng Li, Lianjie Shi, Yingni Li, Hongjiang Liu, Xiaofei Yu, Hongxia Wang, Juan Li, Zhanguo Li, Xiang-Yang Wang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Although myeloid-derived suppressor cells (MDSCs) have been linked to T cell tolerance, their role in autoimmune rheumatoid arthritis (RA) remains elusive. Here we investigate the potential association of MDSCs with the disease pathogenesis using a preclinical model of RA and specimen collected from patients with RA. <h3>Methods</h3> The frequency of MDSCs in blood, lymphoid tissues, inflamed paws or synovial fluid and their association with disease severity, tissue inflammation and the levels of pathogenic T helper (Th) 17 cells were examined in arthritic mice or in patients with RA (n=35) and osteoarthritis (n=15). The MDSCs in arthritic mice were also characterised for their phenotype, inflammation status, T cell suppressive activity and their capacity of pro-Th17 cell differentiation. The involvement of MDSCs in the disease pathology and a Th17 response was examined by adoptive transfer or antibody depletion of MDSCs in arthritic mice or by coculturing mouse or human MDSCs with naïve CD4+ T cells under Th17-polarising conditions. <h3>Results</h3> MDSCs significantly expanded in arthritic mice and in patients with RA, which correlated positively with disease severity and an inflammatory Th17 response. While displaying T cell suppressive activity, MDSCs from arthritic mice produced high levels of inflammatory cytokines (eg, interleukin (IL)-1β, TNF-α). Mouse and human MDSCs promoted Th17 cell polarisation ex vivo. Transfer of MDSCs facilitated disease progression, whereas their elimination in arthritic mice ameliorated disease symptoms concomitant with reduction of IL-17A/Th17 cells. <h3>Conclusions</h3> Our studies suggest that proinflammatory MDSCs with their capacity to drive Th17 cell differentiation may be a critical pathogenic factor in autoimmune arthritis.
An ugly metamorphosis?
Authors: JK Anand
Journal: Journal of the Royal Society of Medicine (2010)

When the Proceedings turned into the JRSM, I mourned the ugly metamorphosis. I still do.

Keep the JRSM, if you must – but, for the sake of the antediluvians like me, split it in to two parts. Let Proceedings be printed and bound in paper and let the ephemera float in the ether – the www world. Then I and other oldies can sit with the proceedings in the armchair or in bed and relish well-written English prose in which are embedded clinical nuggets. Some of us just cannot manage to attend the proceedings!
Stress fracture of the clavicle in a young female gymnast
Authors: K E Fallon, P A Fricker
Journal: British Journal of Sports Medicine (2001)

Stress fractures of the clavicle are rare. This is the report of one such fracture in a 10 year old female gymnast, who presented with a six week history of medial clavicular pain. Radiographs and a computed tomography scan showed an undisplaced fracture through the medial third of the clavicle extending inferiorly to the rhomboid fossa in the inferior aspect of the clavicle. Pathological fracture was excluded by magnetic resonance imaging. The patient was treated conservatively and was able to return to full training eight weeks later.
Subtypes of beta-adrenergic receptors in bovine coronary arteries.
Authors: D E Vatner, D R Knight, C J Homcy, S F Vatner, M A Young
Journal: Circulation Research (1986)

Whether large coronary artery dilation induced by beta-adrenergic stimulation is mediated by beta 1- or beta 2-adrenergic receptors remains controversial. This problem is particularly difficult to address in vivo due to the concomitant increase in coronary blood flow with beta-adrenergic stimulation, which by itself can dilate large coronary arteries. To reconcile this problem, 5 calves were instrumented with intraaortic and intracoronary (i.c.) catheters, ultrasonic diameter transducers, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. Two to six weeks following surgery, beta-adrenergic agonists were administered i.c. to avoid complicating systemic effects. Isoproterenol (0.0025 micrograms/kg, a beta 1 + beta 2-adrenergic agonist) increased coronary diameter (7.1 +/- 0.8% from 5.80 +/- 0.58 mm) (p less than 0.01). Similar increases (p less than 0.01) in coronary diameter occurred with prenalterol (0.4 micrograms/kg, beta 1-adrenergic agonist) (9.5 +/- 1.4%) and pirbuterol (0.25 micrograms/kg, beta 2-adrenergic agonist) (8.1 +/- 1.2%). When coronary blood flow was prevented from rising with the hydraulic constrictor, increases in coronary diameter to all three beta-adrenergic agonists were not attenuated. Large coronary artery dilation with prenalterol and pirbuterol was abolished with beta 1- and beta 2-adrenergic receptor blockade, respectively, while neither beta 1- nor beta 2-adrenergic blockade alone abolished the large coronary artery dilation with isoproterenol. To identify the predominant subtype of beta-adrenergic receptor, competitive inhibition curves utilizing 125I-cyanopindolol (125I-CYP) as the radiolabel versus isoproterenol, epinephrine, and norepinephrine were generated in membrane preparations from calf heart (predominant beta 1), calf lung (predominant beta 2) and calf coronary artery. The coronary artery membrane preparations demonstrated an intermediate pattern. Competition curves with selective beta 1- and beta 2-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both beta-adrenergic receptor subtypes in large coronary arteries, with a ratio of beta 1: beta 2 of 1.5-2.0:1.0. Thus, large coronary arteries of the calf contain both beta 1- and beta 2-adrenergic receptors identified utilizing ligand binding techniques, and stimulation of both receptor subtypes in the intact conscious animal results in large coronary artery dilation, independent of blood-flow-mediated vasodilation.
Mechanism of Apoptosis Induced by the Inhibition of Fatty Acid Synthase in Breast Cancer Cells
Authors: Sucharita Bandyopadhyay, Rui Zhan, Ying Wang, Sudha K. Pai, Shigeru Hirota, Sadahiro Hosobe, Yukio Takano, Ken Saito, Eiji Furuta, Megumi Iiizumi, Sonia Mohinta, Misako Watabe, Charles Chalfant, Kounosuke Watabe
Journal: Cancer Research (2006)

Abstract Fatty acid synthase (FAS) has been found to be overexpressed in a wide range of epithelial tumors, including breast cancer. Pharmacologic inhibitors of FAS cause apoptosis of breast cancer cells and result in decreased tumor size in vivo. However, how the inhibition of FAS induces apoptosis in tumor cells remains largely unknown. To understand the apoptotic pathway resulting from direct inhibition of FAS, we treated breast tumor cells with or without FAS small interfering RNA (siRNA) followed by a microarray analysis. Our results indicated that the proapoptotic genes BNIP3, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), and death-associated protein kinase 2 (DAPK2) were significantly up-regulated on direct inhibition of the FAS gene. We also found that the knockdown of FAS expression significantly increased ceramide level in the tumor cells, and this increase was abrogated by acetyl-CoA carboxylase inhibitor. In addition, carnitine palmitoyltransferase-1 (CPT-1) inhibitor up-regulated the ceramide and BNIP3 levels in these cells, whereas treatment of tumor cells with FAS siRNA in the presence of a ceramide synthase inhibitor abrogated the up-regulation of BNIP3 and inhibited apoptosis. Furthermore, we found that treatment of cells with BNIP3 siRNA significantly counteracted the effect of FAS siRNA-mediated apoptosis. Consistent with these results, a significant inverse correlation was observed in the expression of FAS and BNIP3 in clinical samples of human breast cancer. Collectively, our results indicate that inhibition of FAS in breast cancer cells causes accumulation of malonyl-CoA, which leads to inhibition of CPT-1 and up-regulation of ceramide and induction of the proapoptotic genes BNIP3, TRAIL, and DAPK2, resulting in apoptosis. (Cancer Res 2006; 66(11): 5934-40)
Phospholipase C-γ2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen
Authors: Michele Weber, Bebhinn Treanor, David Depoil, Hisaaki Shinohara, Naomi E. Harwood, Masaki Hikida, Tomohiro Kurosaki, Facundo D. Batista
Journal: The Journal of Experimental Medicine (2008)

B cell receptor (BCR) recognition of membrane-bound antigen initiates a spreading and contraction response, the extent of which is controlled through the formation of signaling-active BCR-antigen microclusters and ultimately affects the outcome of B cell activation. We followed a genetic approach to define the molecular requirements of BCR-induced spreading and microcluster formation. We identify a key role for phospholipase C-γ2 (PLCγ2), Vav, B cell linker, and Bruton's tyrosine kinase in the formation of highly coordinated “microsignalosomes,” the efficient assembly of which is absolutely dependent on Lyn and Syk. Using total internal reflection fluorescence microscopy, we examine at high resolution the recruitment of PLCγ2 and Vav to microsignalosomes, establishing a novel synergistic relationship between the two. Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation.
Parietal Podocytes in Normal Human Glomeruli
Authors: Jean Bariety, Chantal Mandet, Gary S. Hill, Patrick Bruneval
Journal: Journal of the American Society of Nephrology (2006)

Although parietal podocytes along the Bowman’s capsule have been described by electron microscopy in the normal human kidney, their molecular composition remains unknown. Ten human normal kidneys that were removed for cancer were assessed for the presence and the extent of parietal podocytes along the Bowman’s capsule. The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and α-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested. In addition, six normal fetal kidneys were studied to track the ontogeny of parietal podocytes. The podocyte protein labeling detected parietal podocytes in all of the kidneys, was found in 76.6% on average of Bowman’s capsule sections, and was prominent at the vascular pole. WT1 and p57 were expressed in some parietal cells, whereas PAX2 was present in all or most of them, so some parietal cells coexpressed WT1 and PAX2. Furthermore, parietal podocytes coexpressed WT1 and podocyte proteins. Cytokeratin-positive cells covered a variable part of the capsule and did not express podocyte proteins. Tuft-capsular podocyte bridges were present in 15.5 ± 3.7% of the glomerular sections. Parietal podocytes often covered the juxtaglomerular arterioles and were present within the extraglomerular mesangium. Parietal podocytes were present in fetal kidneys. Parietal podocytes that express the same epitopes as visceral podocytes do exist along Bowman’s capsule in the normal adult kidney. They are a constitutive cell type of the Bowman’s capsule. Therefore, their role in physiology and pathology should be investigated.
When does severe diarrhoea disclose a hereditary disease?
Authors: J Boujaoude, K Honein, E Hobeika, C Ghorra, P Ghorra, E Hobeika
Journal: Gut (2007)

A 30-year-old man of Mediterranean origin was admitted for intractable diarrhoea and severe malabsorption. He presented with a 2 month history of frequent watery stools and acute weight loss of 10 kg. He is of Mediterranean origin. His medical history included episodic diffuse abdominal pain of sudden onset, severe intensity …
Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study
Authors: F Cataldo, V Marino, A Ventura, G Bottaro, G R Corazza
Journal: Gut (1998)

Background —Selective immunoglobulin A (IgA) deficiency (SIgAD) is associated with coeliac disease (CD). Aim —To make a retrospective study of the association of SIgAD with CD in Italy. Methods —Hospital medical records of 2098 patients consecutively diagnosed as having CD were reviewed. Results —Of 2098 patients with CD, 54 (2.6%) had SIgAD, representing a 10–16-fold increase over that in the population in general. This increase was not influenced by age or geographical factors. Patients with SIgAD had a higher incidence of silent forms (7/54, 13%), recurrent infections (16/54, 29.6%), and atopic diseases (7/54, 13%) than those without. The association with autoimmune and malignant diseases and the outcome after eating a gluten free diet were similar in patients with or without SIgAD. In all patients with SIgAD, antibodies for IgA gliadin and endomysium were absent, but serum levels of IgG anti-gliadin antibodies were high in almost all of them (51/54). Conclusions —Serum IgA should be measured in order to be able to interpret negative results for IgA anti-gliadin antibodies and anti-endomysial antibodies in patients being screened for CD. Since some patients with CD and SIgAD may be negative for IgG anti-gliadin antibodies, an intestinal biopsy should be performed in all suspected cases.
IL-10 Directly Activates and Expands Tumor-Resident CD8+ T Cells without<i>De Novo</i>Infiltration from Secondary Lymphoid Organs
Authors: Jan Emmerich, John B. Mumm, Ivan H. Chan, Drake LaFace, Hoa Truong, Terrill McClanahan, Daniel M. Gorman, Martin Oft
Journal: Cancer Research (2012)

The presence of activated intratumoral T cells correlates clinically with better prognosis in patients with cancer. Although tumor vaccines can increase the number of tumor-specific CD8(+) T cells in systemic circulation, they frequently fail to increase the number of active and tumor reactive T cells within the tumor. Here we show that treatment with the pleiotropic cytokine interleukin-10 (IL-10) induces specific activation of tumor-resident CD8(+) T cells as well as their intratumoral expansion in several mouse tumor models. We found that inhibition of T-cell trafficking from lymphoid organs did not impair IL-10-induced tumor rejection or the activation of tumor-resident CD8(+) T cells. Tumor-resident CD8(+) T cells expressed elevated levels of the IL-10 receptor and were directly activated by IL-10, resulting in prominent phosphorylation of STAT3 and STAT1. Although CD4(+) T cells, regulatory T cells, NK cells, and dendritic cells have been reported as prominent targets of IL-10 in the tumor microenvironment, we found that expression of the IL-10R was required only on CD8(+) T cells to facilitate IL-10-induced tumor rejection as well as in situ expansion and proliferation of tumor-resident CD8 T cells. Together, our findings indicate that IL-10 activates CD8(+) T-cell-mediated tumor control and suggest that IL-10 may represent a potential tumor immunotherapy in human patients with cancer.
Position in Cell Cycle Controls the Sensitivity of Colon Cancer Cells to Nitric Oxide-Dependent Programmed Cell Death
Authors: Anne Jarry, Laetitia Charrier, Chantal Bou-Hanna, Marie-Claire Devilder, Véronique Crussaire, Marc G. Denis, Geneviève Vallette, Christian L. Laboisse
Journal: Cancer Research (2004)

Abstract Mounting evidence suggests that the position in the cell cycle of cells exposed to an oxidative stress could determine their survival or apoptotic cell death. This study aimed at determining whether nitric oxide (NO)-induced cell death in colon cancer cells might depend on their position in the cell cycle, based on a clone of the cancer cell line HT29 exposed to an NO donor, in combination with the manipulation of the cell entry into the cell cycle. We show that PAPA NONOate (pNO), from 10−4 m to 10−3 m, exerted early and reversible cytostatic effects through ribonucleotide reductase inhibition, followed by late resumption of cell growth at 5 × 10−4 m pNO. In contrast, 10−3 m pNO led to late programmed cell death that was accounted for by the progression of cells into the cell cycle as shown by (a) the accumulation of apoptotic cells in the G2-M phase at 10−3 m pNO treatment; and (b) the prevention of cell death by inhibiting the entry of cells into the cell cycle. The entry of pNO-treated cells into the G2-M phase was associated with actin depolymerization and its S-glutathionylation in the same way as in control cells. However, the pNO treatment interfered with the build-up of a high reducing power, associated in control cells with a dramatic increase in reduced glutathione biosynthesis in the G2-M phase. This oxidative stress prevented the exit from the G2-M phase, which requires a high reducing power for actin deglutathionylation and its repolymerization. Finally, our demonstration that programmed cell death occurred through a caspase-independent pathway is in line with the context of a nitrosative/oxidative stress. In conclusion, this work, which deciphers the connection between the position of colonic cancer cells in the cell cycle and their sensitivity to NO-induced stress and their programmed cell death, could help optimize anticancer protocols based on NO-donating compounds.
Leptin levels are increased and its negative regulators, SOCS-3 and sOb-R are decreased in obese patients with osteoarthritis: a link between obesity and osteoarthritis: Figure 1
Authors: Katriina Vuolteenaho, Anna Koskinen, Teemu Moilanen, Eeva Moilanen
Journal: Annals of the Rheumatic Diseases (2012)

Leptin is a hormone originally discovered in white adipocytes which regulates energy metabolism and appetite. Obese individuals have increased levels of circulating leptin, as compared with their non-obese counterparts, and in mouse models, leptin deficiency causes morbid obesity.1 However, due to the appearance of leptin resistance in the hypothalamus, increased blood levels of leptin in obese subjects fail to induce the expected responses to high leptin, that is, increased energy expenditure, reduced food intake and decreased body weight.2 Leptin resistance has been shown to be mediated by an increased expression of the suppressor of cytokine signalling-3 (SOCS-3).1 ,2

Obesity has been thought to contribute to the development of osteoarthritis (OA) by increasing the load on weight-bearing joints. However, this appears to be an over-simplification, since obesity is also linked to …