tbuckley/cabot-search huggingface dataset:
Hip Fracture Incidence in Relation to Age, Menopausal Status, and Age at Menopause: Prospective Analysis
Authors: Emily Banks, Gillian K. Reeves, Valerie Beral, Angela Balkwill, Bette Liu, Andrew Roddam
Journal: PLoS Medicine (2009)

Background Bone mineral density is known to decrease rapidly after the menopause. There is limited evidence about the separate contributions of a woman's age, menopausal status and age at menopause to the incidence of hip fracture. Methods and Findings Over one million middle-aged women joined the UK Million Women Study in 1996–2001 providing information on their menopausal status, age at menopause, and other factors, which was updated, where possible, 3 y later. All women were registered with the UK National Health Service (NHS) and were routinely linked to information on cause-specific admissions to NHS hospitals. 561,609 women who had never used hormone replacement therapy and who provided complete information on menopausal variables (at baseline 25% were pre/perimenopausal and 75% postmenopausal) were followed up for a total of 3.4 million woman-years (an average 6.2 y per woman). During follow-up 1,676 (0.3%) were admitted to hospital with a first incident hip fracture. Among women aged 50–54 y the relative risk (RR) of hip fracture risk was significantly higher in postmenopausal than premenopausal women (adjusted RR 2.22, 95% confidence interval [CI] 1.22–4.04; p = 0.009); there were too few premenopausal women aged 55 y and over for valid comparisons. Among postmenopausal women, hip fracture incidence increased steeply with age (p<0.001), with rates being about seven times higher at age 70–74 y than at 50–54 y (incidence rates of 0.82 versus 0.11 per 100 women over 5 y). Among postmenopausal women of a given age there was no significant difference in hip fracture incidence between women whose menopause was due to bilateral oophorectomy compared to a natural menopause (adjusted RR 1.20, 95% CI 0.94–1.55; p = 0.15), and age at menopause had little, if any, effect on hip fracture incidence. Conclusions At around the time of the menopause, hip fracture incidence is about twice as high in postmenopausal than in premenopausal women, but this effect is short lived. Among postmenopausal women, age is by far the main determinant of hip fracture incidence and, for women of a given age, their age at menopause has, at most, a weak additional effect. Please see later in the article for the Editors' Summary
Effects of the Administration of High-Dose Interleukin-2 on Immunoregulatory Cell Subsets in Patients with Advanced Melanoma and Renal Cell Cancer
Authors: Hans J.J. van derVliet, Henry B. Koon, Simon C. Yue, Burak Uzunparmak, Virginia Seery, Marc A. Gavin, Alexander Y. Rudensky, Michael B. Atkins, Steven P. Balk, Mark A. Exley
Journal: Clinical Cancer Research (2007)

Abstract Purpose: High-dose recombinant human interleukin-2 (IL-2) therapy is of clinical benefit in a subset of patients with advanced melanoma and renal cell cancer. Although IL-2 is well known as a T-cell growth factor, its potential in vivo effects on human immunoregulatory cell subsets are largely unexplored. Experimental Design: Here, we studied the effects of high-dose IL-2 therapy on circulating dendritic cell subsets (DC), CD1d-reactive invariant natural killer T cells (iNKT), and CD4+CD25+ regulatory-type T cells. Results: The frequency of both circulating myeloid DC1 and plasmacytoid DC decreased during high-dose IL-2 treatment. Of these, only a significant fraction of myeloid DC expressed CD1d. Although the proportion of Th1-type CD4− iNKT increased, similarly to DC subsets, the total frequency of iNKT decreased during high-dose IL-2 treatment. In contrast, the frequency of CD4+CD25+ T cells, including CD4+Foxp3+ T cells, which have been reported to suppress antitumor immune responses, increased during high-dose IL-2 therapy. However, there was little, if any, change of expression of GITR, CD30, or CTLA-4 on CD4+CD25+ T cells in response to IL-2. Functionally, patient CD25+ T cells at their peak level (immediately after the first cycle of high-dose IL-2) were less suppressive than healthy donor CD25+ T cells and mostly failed to Th2 polarize iNKT. Conclusions: Our data show that there are reciprocal quantitative and qualitative alterations of immunoregulatory cell subsets with opposing functions during treatment with high-dose IL-2, some of which may compromise the establishment of effective antitumor immune responses.
Adult obesity and growth in childhood
Authors: D. Simmons
Journal: BMJ (2002)

Editor—Parsons et al highlight the importance of maternal weight on birth weight and future obesity in the offspring.1 They emphasise the importance of genetics and debate the relation between reduced intrauterine growth on future obesity but do not discuss the role of fuel mediated teratogenesis during fetal development.2

Fuel mediated teratogenesis proposes that intrauterine exposure of the fetus of women with diabetes in pregnancy to an excess of fuel (for example, glucose) causes permanent fetal change, leading to malformations, greater birth weight, and an increased risk of developing type 2 diabetes in later life.2 More recently, obesity in the offspring has been included as an outcome of fuel mediated teratogenesis in pregnancies complicated by diabetes.3,4 However, maternal fuel supply across a population is a continuum, and the criteria for gestational diabetes may not be sufficient to differentiate between a diabetogenic and a non-diabetogenic intrauterine milieu.

We investigated the relation between first trimester body mass index and glycaemia at 36 weeks' gestation and birth weight and umbilical cord insulin concentrations in the pregnancies of 63 Polynesian women without gestational diabetes.5 We found that the greater the maternal body mass index (divided into thirds (<25.0, 25.0-31.7, ⩾31.8 kg/m2)) the bigger the baby, the higher the maternal fasting glucose concentration (5.1 (SD 0.6), 5.0 (0.5), 5.3 (0.5) mmol/l; P=0.097), and the higher the geometric mean of the umbilical cord insulin concentration (10.0, 14.0, 14.9 μmol/l; P=0.015). There were no differences across the thirds of body mass index in concentrations of cord leptin or insulin-like growth factor-I.

We hypothesised that increasing maternal obesity is associated with increasing maternal glycaemia, thereby stimulating fetal insulin secretion and raising the potential for obesity in the offspring. As plasma glucose is a continuous variable the relation between glycaemia and the future development of diabetes and obesity in the offspring that is found in diabetes in pregnancy3,4 is also likely to be present in those offspring at the upper end of the normal range. This is relevant for the debate over diagnostic criteria and management of gestational diabetes.

The public health implications of the hypothesis that fuel mediated teratogenesis may be driven by maternal obesity are enormous. If the hypothesis is confirmed attention should be directed towards controlling obesity and maximising fitness among women before pregnancy. More aggressive approaches to hyperglycaemia during pregnancy through a lowering of the criteria for gestational diabetes and more widespread use of insulin treatment in gestational diabetes may also need to be considered.
Intestinal Phospholipase, a Novel Enzyme
Authors: Charles M. Mansbach, Gerard Pieroni, Robert Verger
Journal: Journal of Clinical Investigation (1982)

We evaluated phospholipase activity in the intestine of rats and other species. Phospholipase activity was assayed by a surface barostat technique or an egg yolk titration system. Mucosal activity was found only by the surface barostat technique with phosphatidylglycerol as substrate; it was not found with phosphatidylcholine as substrate in assays by either technique. In gut luminal fluid activity was found when both phosphatidylcholine and phosphatidylglycerol were used as substrate in assays by the surface barostat technique, and phosphatidylcholine as substrate yielded activity in egg yolk titration. In rats in which pancreatic juice had been diverted, mucosal and gut luminal phospholipase activity was greater than in controls, thus demonstrating that enzyme activity was not due to pancreatic phospholipase. Bacterial origin of phospholipase activity was excluded in that phospholipase activity was found in germ-free rats; gastric and salivary gland origins were excluded in that continued phospholipase activity was found in rats with gastric fistula. The physiological importance of the enzyme was established by the finding that rats with pancreatic fistula absorbed 111 μmol of phosphatidylcholine and that controls absorbed 119 μmol of a 135-μmol load. Activity was found to be three times greater in the distal than in the proximal intestine; in cryptal cells it was 10 times greater than in villus tip cells. 65% of the activity in the gut lumen was tightly bound to particulate matter. We propose that intestinal phospholipase may be important in gut bacterial control, in the digestion of vegetable matter (phosphatidylglycerol is a major phospholipid in both plants and bacteria), and in the digestion of phospholipids in the gut lumen.
Value of Magnetic Resonance Spectroscopy Imaging and Dynamic Contrast-Enhanced Imaging for Detecting Prostate Cancer Foci in Men With Prior Negative Biopsy
Authors: Alessandro Sciarra, Valeria Panebianco, Mauro Ciccariello, Stefano Salciccia, Susanna Cattarino, Danilo Lisi, Alessandro Gentilucci, Andrea Alfarone, Silvia Bernardo, Roberto Passariello, Vincenzo Gentile
Journal: Clinical Cancer Research (2010)

This study aimed to prospectively analyze the role of magnetic resonance spectroscopy imaging (MRSI) and dynamic-contrast enhancement magnetic resonance (DCEMR) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels (in the range of >or=4 ng/mL to <10 ng/mL) and prior negative random trans-rectal ultrasound (TRUS)-guided biopsy.This was a prospective randomized single-center study. One hundred and eighty eligible cases were included in the study. Patients in group A were submitted to a second random prostate biopsy, whereas patients in group B were submitted to a (1)H-MRSI-DCEMR examination and samples targeted on suspicious areas were associated to the random biopsy.At the second biopsy, a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases (24.4%) in group A and in 41 of 90 cases (45.5%) in group B (P = 0.01). On a patient-by-patient basis, MRSI had 92.3% sensitivity, 88.2% specificity, 85.7% positive predictive value (PPV), 93.7% negative predictive value (NPV), and 90% accuracy; DCEMR had 84.6 % sensitivity, 82.3% specificity, 78.5% PPV, 87.5% NPV, and 83.3% accuracy; and the association MRSI plus DCEMR had 92.6% sensitivity, 88.8% specificity, 88.7% PPV, 92.7% NPV, and 90.7% accuracy, for predicting prostate cancer detection.The combination of MRSI and DCEMR showed the potential to guide biopsy to cancer foci in patients with previously negative TRUS biopsy. To avoid a potential bias, represented from having taken more samples in group B (mean of cores, 12.17) than in group A (10 cores), in the future a MRSI/DCEMR directed biopsy could be prospectively compared with a saturation biopsy procedure.
High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice.
Authors: J Huard, S Verreault, R Roy, M Tremblay, J P Tremblay
Journal: Journal of Clinical Investigation (1994)

SCID mouse tibialis anterior muscles were first irradiated to prevent regeneration by host myoblasts and injected with notexin to damage the muscle fibers and trigger regeneration. The muscles were then injected with roughly 5 million human myoblasts. 1 mo later, 16-33% of the normal number of muscle fibers were present in the injected muscle, because of incomplete regeneration. However, > 90% of these muscle fibers contained human dystrophin. Some newly formed muscle fibers had an accumulation of human dystrophin and desmin on a part of their membrane. Such accumulations have been demonstrated at neuromuscular junctions before suggesting that the new muscle fibers are innervated and functional. The same pool of clones of human myoblasts produced only < or = 4% of muscle fibers containing human dystrophin when injected in nude mice muscles. Several of the human myoblasts did not fuse and remained in interstitial space or tightly associated with muscle fibers suggesting that some of them have formed satellite cells. Moreover, cultures of 98% pure human myoblasts were obtained from transplanted SCID muscles. In some mice where the muscle regeneration was not complete, the muscle fibers containing human dystrophin also expressed uniformly HLA class 1, confirming that the fibers are of human origin. The presence of hybrid muscle fibers containing human dystrophin and mouse MHC was also demonstrated following transplantation. These results establish that in absence of an immune reaction, transplanted human myoblasts participate to the muscle regeneration with a high degree of efficacy even if the animals were killed only 1 mo after the transplantation.
STUDIES ON VITAL STAINING
Authors: F. B. Davies, R. C. Wadsworth, H. P. Smith
Journal: The Journal of Experimental Medicine (1930)

Vital staining reactions of brilliant vital red and Niagara sky blue are studied in dogs and in rabbits. Either dye alone is taken up to form red or blue granules within the cytoplasm of macrophages and of certain other cell types. When the two dyes are injected simultaneously into the blood stream one finds that these cells build up granules which are purple from admixture of the two dyes. When several daily injections of one dye are followed by several daily injections of the other, one finds blue granules and red granules side by side within the cells, but no purple granules are found. This is thought to indicate that the dye is deposited in small foci which are active in a rather transitory way, and that the color of the granule is determined during its formative stage by the type of dye present in the fluids about the cell. The enlargement of phagocytic cells and the increase in their number with large dosage, or with repeated offerings of the dye, represents a method by which the cells maintain their phagocytic powers at the normal level. Evidence is offered to indicate that these and perhaps other compensatory changes may take place with great rapidity, so that it has been impossible to "block" or even reduce noticeably the ability of these cells to take up additional quantities of dye. Certain pitfalls in the experimental study of "blockade" are pointed out.
Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma
Authors: B. Neyns, J. Sadones, E. Joosens, F. Bouttens, L. Verbeke, J.-F. Baurain, L. D'Hondt, T. Strauven, C. Chaskis, P. In't Veld, A. Michotte, J. De Greve
Journal: Annals of Oncology (2009)
Cancer Survivors’ Adherence to Lifestyle Behavior Recommendations and Associations With Health-Related Quality of Life: Results From the American Cancer Society's SCS-II
Authors: Christopher M. Blanchard, Kerry S. Courneya, Kevin Stein
Journal: Journal of Clinical Oncology (2008)

To examine the prevalence and clustering of physical activity (PA), fruit and vegetable consumption (5-A-Day), and smoking across six major cancer survivor groups and to identify any associations with health-related quality of life (HRQoL).A total of 9,105 survivors of six different cancers completed a national cross-sectional survey that included the lifestyle behavior questions and the RAND-36 Health Status Inventory.Only a minority of cancer survivors were meeting the 5-A-Day (14.8% to 19.1%) or PA (29.6% to 47.3%) recommendations, whereas most were meeting the smoking recommendation (82.6% to 91.6%). In terms of the lifestyle behavior clusters, only 5% of cancer survivors were meeting all three recommendations. Analyses of covariance generally showed higher HRQoL in survivors who were meeting versus not meeting each lifestyle behavior recommendation with the strongest associations emerging for PA. Trend analyses showed a steep positive association between the number of lifestyle behavior recommendations being met and HRQoL for breast (P < .001), prostate (P < .001), colorectal (P < .001), bladder (P < .001), uterine (P < .001), and skin melanoma (P < .001) cancer survivors.Few cancer survivors are meeting the PA or 5-A-Day recommendations, and even fewer are meeting all three lifestyle recommendations. The association between the current lifestyle recommendations and HRQoL in cancer survivors appears to be cumulative. Interventions to increase PA and fruit and vegetable consumption and reduce smoking are warranted and may have additive effects on the HRQoL of cancer survivors.
Airway injury during high-level exercise
Authors: Pascale Kippelen, Sandra D Anderson
Journal: British Journal of Sports Medicine (2012)

Airway epithelial cells act as a physical barrier against environmental toxins and injury, and modulate inflammation and the immune response. As such, maintenance of their integrity is critical. Evidence is accumulating to suggest that exercise can cause injury to the airway epithelium. This seems the case particularly for competitive athletes performing high-level exercise, or when exercise takes place in extreme environmental conditions such as in cold dry air or in polluted air. Dehydration of the small airways and increased forces exerted on to the airway surface during severe hyperpnoea are thought to be key factors in determining the occurrence of injury of the airway epithelium. The injury-repair process of the airway epithelium may contribute to the development of the bronchial hyper-responsiveness that is documented in many elite athletes.
Short incubation with 7-oxo-prostacyclin induces long lasting prolongation of repolarisation time and effective refractory period in rabbit papillary muscle preparation
Authors: L Szekeres, M Nemeth, J G Papp, E. Udvary
Journal: Cardiovascular Research (1990)

Study objective – To determine whether the long lasting protection from early postocclusion and reperfusion arrhythmias induced by 7-oxo-prostacyclin is due to an anti-ischaemic effect alone or in combination with direct membrane effects. Design – The study was performed on electrically stimulated isolated rabbit papillary muscle preparations with or without incubation with a stable prostacyclin analogue, 7-oxo-prostacyclin-ephedrine (7-oxo-PgI2). In some experiments, rabbits were pretreated with 7-oxo-PgI2. Measurements and results – Marked prolongation of action potential duration (APD90) and effective refractory period developed 2 h after 20 min incubation with and subsequent washout of 7-oxo-PgI2, 1.1 × 10−8 mol.litre−1. The same occurred if incubation with 7-oxo-PgI2 was maintained throughout the experiment. The only other change was a small diminution in amplitude of the action potential. During the 20 min incubation period neither APD90 nor effective refractory period was affected and only a transitory increase in the maximum rate of depolarisation, disappearing after washout, was seen. During the 4 h observation period there were no changes in the control preparations. The long lasting electrophysiological changes induced by 7-oxo-PgI2 were not affected by 60 min incubation with indomethacin, 2.8 × 10−6 mol.litre−1. Pretreatment of rabbits with 7-oxo-PgI2, 50 μg.kg−1 intramuscularly, 48 h before the experiments prolonged effective refractory period ν, untreated controls. Conclusions – 7-oxo-PgI2 induces prolongation of APD90 and effective refractory period in adequately oxygenated normal papillary muscles as well as in ischaemic hearts. Therefore a direct membrane effect may contribute to its antiarrhythmic action, as well as an indirect anti-ischaemic effect. Such a direct effect is unlikely to be related to activation of the degradation products of the arachidonic acid cascade since it was not influenced by indomethacin.
Antigen-independent activation of naive and memory resting T cells by a cytokine combination.
Authors: D Unutmaz, P Pileri, S Abrignani
Journal: The Journal of Experimental Medicine (1994)

We investigated whether human resting T cells could be activated to proliferate and display effector function in the absence of T cell receptor occupancy. We report that combination of interleukin 2 (IL-2), tumor necrosis factor alpha, and IL-6 activated highly purified naive (CD45RA+) and memory (CD45RO+) resting CD4+ T cells to proliferate. Under this condition, memory resting T cells could also display effector function as measured by lymphokine synthesis and help for immunoglobulin production by B cells. This novel Ag-independent pathway of T cell activation may play an important role in vivo in recruiting effector T cells at the site of immune response and in maintaining the clonal size of memory T cells in the absence of antigenic stimulation. Moreover, cytokines can induce proliferation of naive T cells without switch to memory phenotype and this may help the maintenance of the peripheral pool of naive T cells.
Malaria, the Red Cell, and the Endothelium
Authors: Brittan L. Pasloske, Russell J. Howard
Journal: Annual Review of Medicine (1994)

▪ Abstract Erythrocytes infected with mature stages of Plasmodium falciparum malaria adhere to vascular endothelial cells in postcapillary venules of several organs. In some patients, infected cells also form rosettes with uninfected erythrocytes. The special pathology of acute cerebral malaria appears to result from excessive adherence of infected cells in cerebral vessels coupled with occlusion of cerebral blood flow in microvessels by infected cell rosettes. Several endothelial cell proteins have been identified as potential receptors for infected erythrocyte adherence to vascular endothelium, including thrombospondin, CD36, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). The receptor on infected erythrocytes that mediates adhesion to endothelial cells has been identified as a very large malarial protein on infected cells called PfEMP1. PfEMP1 has been shown to bind to CD36 and thrombospondin in vitro. Antibody-mediated blockade or reversal of infected erythrocyte adherence to vascular endothelium is postulated not only to decrease the pathology of blood-stage malaria, but also to lead to infected cell destruction and clearance, especially in the spleen. PfEMP1 is therefore a prime candidate malarial protein for inclusion in a multicomponent asexual malaria vaccine.