tbuckley/cabot-search huggingface dataset:
Weight Gain Is Associated with Increased Risk of Hot Flashes in Breast Cancer Survivors on Aromatase Inhibitors.
Authors: H. Su, H. Su, M. Sammel, E. Springer, E. Freeman, A. DeMichele, A. DeMichele, J. Mao, J. Mao
Journal: Cancer Research (2009)

Abstract Objective: Hot flashes in breast cancer survivors (BCS) receiving adjuvant aromatase inhibitor (AI) therapy are common, but risk factors for these symptoms are not well-defined. This study tested if body size is associated with hot flashes in BCS on AI therapy.Materials and methods: We performed a cross-sectional analysis of a cohort of postmenopausal women with Stages 0-III breast cancer receiving adjuvant AI therapy at a university hospital-based outpatient breast oncology clinic. Subjects provided patient-reported outcomes on hot flashes, current and pre-breast cancer weight and height, and additional demographic and treatment data.The primary outcome was occurrence of hot flashes. Secondary outcomes included hot flash severity and frequency. The exposures of interest were 1) current weight and 2) weight change since breast cancer diagnosis, categorized as weight loss (lost 10 pounds or more), maintenance (+/- 10 pounds), or gain (gained 10 pounds or more). Multivariable logistic regression models examined the independent association between hot flash outcomes and current weight or weight change while controlling for confounders.Results: 300 participants were enrolled at a mean age of 61 years (range 33-86) after mean duration of AI exposure of 23 months (range 1 month-9 years). 177 (59%) reported hot flashes overall, 96 (32%) reported moderate to very severe hot flashes, and 60 (20%) had at least 4 hot flashes daily. 182 (61%) experienced weight maintenance, while 81 (27%) had weight gain and 34 (11%) had weight loss. In a multivariable model, weight gain was independently associated with hot flash occurrence (OR 2.1, 95% CI 1.1-4.4) and hot flash severity (OR 2.4, 95% CI 1.4-4.9), but not hot flash frequency, after adjusting for current weight and height, age, smoking, race, prior chemotherapy and prior tamoxifen therapy. Hot flash occurrence was also significantly associated with current smoking (OR 5.1, 95% CI 1.1-24.0) and age (OR for each additional year of age 0.93, 95% CI 0.90-0.97). Current weight, alcohol use, AI type, and AI duration were not associated with any of the three outcomes.Conclusions: In an outpatient BCS population on AI therapy, weight gain is a risk factor for both hot flash occurrence and severity. Women who gained at least ten pounds since breast cancer diagnosis were two times more likely to have hot flashes than women who maintained or lost weight. These results support the thermoregulatory model of hot flashes and argue against a protective effect of body fat in this population.Support: ACS MRSG-08-110-01-CCE, ACS CCDA#-08-107-01, Pennsylvania Department of Aging Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1059.
Identification of proliferating dendritic cell precursors in mouse blood.
Authors: K Inaba, R M Steinman, M W Pack, H Aya, M Inaba, T Sudo, S Wolpe, G Schuler
Journal: The Journal of Experimental Medicine (1992)

While it has been known that dendritic cells arise from proliferating precursors in situ, it has been difficult to identify progenitors in culture. We find that aggregates of growing dendritic cells develop in cultures of mouse blood that are supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF) but not other CSFs. The dendritic cell precursor derives from the Ia-negative and nonadherent fraction. The aggregates of developing dendritic cells appear at about 1 wk of culture, with 100 or more such clusters being formed per 10(6) blood leukocytes. The aggregates can be dislodged and subcultured as expanding clusters that are covered with cells having the motile sheet-like processes ("veils") of dendritic cells. By about 2 wk, large numbers of single, major histocompatibility complex (MHC) class II-rich dendritic cells begin to be released into the medium. Combined immunoperoxidase and [3H]thymidine autoradiography show that the cells that proliferate within the aggregate lack certain antigenic markers that are found on mature dendritic cells. However, in pulse-chase protocols, the [3H]thymidine-labeled progeny exhibit many typical dendritic cell features, including abundant MHC class II and a cytoplasmic granular antigen identified by monoclonal antibody 2A1. The progeny dendritic cells are potent stimulators of the mixed leukocyte reaction and can home to the T-dependent areas of lymph node after injection into the footpads. We conclude that mouse blood contains GM-CSF-dependent, proliferating progenitors that give rise to large numbers of dendritic cells with characteristic morphology, mobility, phenotype, and strong T cell stimulatory function.
852. Chromatin Study of Adenovirus Vector DNA In Vivo
Authors: Dan Cao, Mark A. Kay
Journal: Molecular Therapy (2006)

Recombinant adenoviral vectors are robust at transgene expression in a wide variety of tissues including the liver. While adenoviral- mediated transgene expression can be persistent in the absence of toxicity, very little is know about the structure of the adenoviral genome once it enters the nucleus. Our interest is related to the chromatin structure of both 1st generation and gene-deleted adenoviral vectors in vivo. We have previously established that intact plasmid DNAs that are silenced have a different chromatin structure than minicircle DNAs devoid of bacterial plasmid DNA sequences, which are persistently active in vivo. We hypothesized that upon entering the nucleus, adenoviral DNA will be packaged in cellular histones and form chromatin structures similar to those observed with transcriptionally active plasmid DNAs. By using chromatin immunoprecipitation (CHIP), we have begun comparing the chromatin modifications of adenoviral vector, plasmid, and minicircle DNAs over the course of time after vector administration into mouse liver. Our preliminary results show differences in histone modifications between adenoviral genomes and plasmid DNAs. Further analyses should allow us to determine if histone modifications play a role in transgene expression from episomal vectors in vivo.
Budget lays bare full cost to public services of economic crisis
Authors: N. Timmins
Journal: BMJ (2009)

A severe and long public sector recession is in prospect in the wake of the private sector recession, as the UK government moves to pay back the mountain of debt accumulating as tax revenues fall and as it keeps up spending to combat the downturn.

Borrowing is expected to total £348bn (€390bn; $510bn) over the next two years, three and a half times the annual cost of the NHS in England. It will have to be serviced and paid back. The return of growth will help, but a large part of the bill will have to be met by a mixture of tax rises and spending cuts.

Cuts will be harsh. Alistair Darling, the chancellor, set out an overall freeze in public spending for the three years from April 2011, with a cash cut of a half in capital expenditure, down from £44bn this year to £22bn a year by 2013-4. Current expenditure will rise by just 0.7% in …
Measurement of growth hormone-releasing hormone and somatostatin in hypothalamic-portal plasma of unanesthetized sheep. Spontaneous secretion and response to insulin-induced hypoglycemia.
Authors: L A Frohman, T R Downs, I J Clarke, G B Thomas
Journal: Journal of Clinical Investigation (1990)

To elucidate the role of growth hormone (GH)-releasing hormone (GRH) and somatostatin (SRIH) in the regulation of the growth hormone (GH) secretory pattern, we collected portal blood from five unanesthetized ovariectomized ewes for repeated measurements of GRH and SRIH simultaneous with those of peripheral GH. Hormones were measured at 10-min intervals for 5.5 h and their interrelationships analyzed. Mean portal GRH was 20.4 +/- 6.7 (SD) pg/ml and the estimated overall secretion rate was 13 pg/min. GRH secretion was pulsatile with peaks of 25-40 pg/ml and a mean pulse interval of 71 min. Mean portal SRIH was 72 +/- 33 pg/ml and the estimated overall secretion rate was 32 pg/min. SRIH secretion was also pulsatile with peaks of 65-160 pg/ml and a mean pulse interval of 54 min. The GH pulse interval was 62 min. A significant association was present between GRH and GH secretory peaks though not between GRH and SRIH or SRIH and GH. Insulin hypoglycemia resulted in a rapid and brief stimulation of SRIH secretion followed by a decline in GH levels. No effect was observed on GRH secretion until 90 min, when a slight increase occurred. The results suggest (a) the presence of an independent neural rhythmicity of GRH and SRIH secretion with a primary role of GRH in determining pulsatile GRH secretion, and (b) that the inhibitory effects of insulin hypoglycemia on GH in this species are attributable to a combination of enhanced SRIH secretion and possibly other factors, though without significant inhibition of GRH.
Levodopa and Pyridoxine-Deficient States
Authors: Steven Arthur Friedman
Journal: JAMA (1970)

<h3>To the Editor.—</h3> On theoretical grounds, extra attention should be paid to patients with Parkinson's disease being considered for levodopa therapy who also have conditions rendering them relatively pyridoxine deficient. Among the conditions associated with relative pyridoxine deficiencies are certain illnesses (diabetes mellitus, chronic alcoholism, malnutrition, and malignancies), industrial exposures (hydrazine-containing rocket fuels<sup>1</sup>), and drug therapies (isoniazid<sup>2</sup>or cycloserine<sup>3</sup>for tuberculosis and penicillamine<sup>4</sup>for Wilson's disease, cystinuria, and heavy metal intoxication). In patients with these conditions, supplemental pyridoxine hydrochloride is often used. Several investigators have now reported that pyridoxine antagonizes the beneficial effects of levodopa,<sup>5-8</sup>and at least one multiple vitamin preparation without pyridoxine is now available because of this. The Food and Drug Administration, in releasing levodopa, has required the manufacturers to continue reporting upon its clinical efficacy and hazards. Because I am not aware of any completed documentation of the interaction of levodopa with
Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels, Qatar, April 2014
Authors: C B Reusken, E A Farag, M Jonges, G J Godeke, A M El-Sayed, S D Pas, V S Raj, K A Mohran, H A Moussa, H Ghobashy, F Alhajri, A K Ibrahim, B J Bosch, S K Pasha, H E Al-Romaihi, M Al-Thani, S A Al-Marri, M M AlHajri, B L Haagmans, M P Koopmans
Journal: Eurosurveillance (2014)

Antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) were detected in serum and milk collected according to local customs from 33 camels in Qatar, April 2014. At one location, evidence for active virus shedding in nasal secretions and/or faeces was observed for 7/12 camels; viral RNA was detected in milk of five of these seven camels. The presence of MERS-CoV RNA in milk of camels actively shedding the virus warrants measures to prevent putative food-borne transmission of MERS-CoV.
Critical role for a high-affinity chemokine-binding protein in γ-herpesvirus–induced lethal meningitis
Authors: Victor van Berkel, Beth Levine, Sharookh B. Kapadia, James E. Goldman, Samuel H. Speck, Herbert W. Virgin IV
Journal: Journal of Clinical Investigation (2002)

Chemokines are involved in recruitment and activation of hematopoietic cells in sites of infection and inflammation. The M3 gene of the γ-herpesvirus γHV68 encodes an abundant secreted protein that binds CC chemokines with high affinity. We report here that this gene is essential for efficient induction of lethal meningitis by γHV68. An M3 mutant γHV68 (γHV68-M3.stop) was 100-fold less virulent than wild-type or marker rescue control (γHV68-M3.MR) viruses after intracerebral inoculation. After intracerebral inoculation, γHV68-M3.stop grew to lower titers than γHV68 or γHV68-M3.MR in the brain but spread to and grew normally in the spleen and lung. Expression of several CC chemokines was significantly induced in the CNS by γHV68 infection. Consistent with M3 acting by blockade of CC chemokine action, γHV68 induced a neutrophilic meningeal inflammatory infiltrate, while γHV68-M3.stop induced an infiltrate in which lymphocytes and macrophages predominated. In contrast to the important role of M3 in lethal meningitis, M3 was not required for establishment or reactivation from latent infection or induction of chronic arteritis. These data suggest a role for chemokines in the protection of the nervous system from viral infection and that the M3 protein acts in a tissue-specific fashion during acute but not chronic γHV68 infection to limit CC chemokine–induced inflammatory responses.
CD166pos Subpopulation From Differentiated Human ES and iPS Cells Support Repair of Acute Lung Injury
Authors: Boon Seng Soh, Dahai Zheng, Julie Su Li Yeo, Henry He Yang, Shi Yan Ng, Lan Hiong Wong, Wencai Zhang, Pin Li, Massimo Nichane, Atasha Asmat, Poo Sing Wong, Peng Cheang Wong, Lin Lin Su, Sakis A Mantalaris, Jia Lu, Wa Xian, Frank McKeon, Jianzhu Chen, Elaine Hsuen Lim, Bing Lim
Journal: Molecular Therapy (2012)

Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation. Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation.
GRANULES IN THE CELLS OF CHICK EMBRYOS PRODUCED BY EGG ALBUMIN IN THE MEDIUM OF TISSUE CULTURES
Authors: Margaret Reed Lewis
Journal: The Journal of Experimental Medicine (1921)

It is difficult to understand what factors may be concerned in the formation of the al. granules. The phenomenon may be concerned with changes in the cell membrane due to an abnormal environment; that is, material which would otherwise be excluded may be permitted to enter the cell, or, on the other hand, certain substances may be prevented from passing out of the cells. Previous investigators have shown that mesenchyme cells sometimes engulf certain foreign bodies, and it is possible that the solution of white of egg is ingested in the same manner. When a solution of peptone was placed on the cells instead of egg white, the phenomenon did not occur (Fig. 13); the cell remained normal and degenerated in the usual manner (Fig. 14). This would seem to indicate that the al. granules are not formed from peptone. Regardless of the factors involved, it is evident that egg albumin in the medium of tissue cultures of chick embryos causes the formation of numerous large granules in the cytoplasm of the connective tissue cells. This phenomenon is associated with unfavorable conditions for the life of the cells and results in the rapid death of the cultures.
Asymmetric septal hypertrophy and myocardial fiber disarray. Features of normal, developing, and malformed hearts.
Authors: B H Bulkley, M L Weisfeldt, G M Hutchins
Journal: Circulation (1977)

The specificity and significance of the asymmetric septal hypertrophy (ASH) and myocardial fiber disarray of idiopathic hypertrophic subaortic stenosis (IHSS) is uncertain. To examine this we studied 215 hearts, including normal embryos, fetuses, children, and adults; and hearts with congenital and acquired disease. Disproportionate septal thickening was present in all embryos and in some abnormal hearts, particularly those with severe right ventricular hypertrophy due to congenital malformations. Some myocardial fiber disarray was present in all hearts at the junctions of interventricular septum and ventricular free wall. In hearts with semilunar valve atresia with intact ventricular septums, and in the infundibulum of some with tetralogy of Fallot, however, extensive fiber disarray was present. Thus, ASH occurs in the normal developing heart and in some malformed hearts with RVH; marked muscle fiber disarray may occur in certain congenital lesions with abnormal systolic contraction. Neither morphologic finding independently or in combination is pathognomonic of idiopathic hypertrophic subaortic stenosis.
MILK INJECTIONS WITHOUT LOCAL REACTIONS
Authors: K. D. Graves
Journal: JAMA (1924)

Without going into the use of milk hypodermically as a foreign protein, I will merely say that it is one of the most widely used materials we have for this purpose, because of its availability. Following the hypodermic use of milk, I have observed that almost invariably the arm of the patient becomes tender and red at the site of injection, often extending over a space 5 or more cm. in diameter, beginning in a few hours, and often lasting several days. Owing to the similarity of this reaction to that following the injection of lipovaccine used in the army at one time, I decided to try fat-free milk instead of whole milk. This has given splended results, the local reaction being practically nil. Milk is centrifugated, and care is taken to load the syringe with milk well below the cream line. It appears that the cream is undesirable, as
PRELIMINARY CLINICAL EVALUATION OF THROMBIN RECOVERY TEST
Authors: L. A. Sternberger
Journal: JAMA (1952)

The laboratory diagnosis of thrombosis has been difficult because of the absence in circulating blood of the two essential products of coagulation, thrombin and fibrin. The fibrin is fixed at a local site, while the excess of thrombin formed becomes inactivated immediately by antithrombic substances. Recently a method for recovering such inactivated thrombin has been developed,<sup>1</sup>and elevated values have been demonstrated in thrombosis produced experimentally in rabbits. The method has now been applied to patients, and the present paper reports on these clinical observations. <h3>METHODS</h3> The recovery of thrombin is accomplished by dissociating the thrombin-antithrombin complex with alkali slightly above freezing temperature and by preventing its reassociation upon neutralization through the addition of ethyl alcohol to a final concentration of 25%. Nine milliliters of venous blood are obtained with siliconized syringes<sup>2</sup>containing 1.0 ml. of 4% sodium citrate solution. Siliconized needles (19 gauge) are used. The plasma
Bleeding after Cardiopulmonary Bypass
Authors: Laurence A. Harker
Journal: New England Journal of Medicine (1986)

Patients who undergo heart surgery and cardiopulmonary bypass with a pump oxygenator are at substantial risk of serious postoperative bleeding; they often require blood-component therapy, although reoperation for bleeding is necessary for only about 1 in 20 patients. The excessive bleeding is related to both the surgical damage to blood vessels and acquired acute defects in hemostasis.1 2 3 The hemorrhagic diathesis produced by cardiopulmonary bypass has been difficult to characterize because of the complexity of the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled physiologic variables associated with cardiopulmonary bypass. These variables include the effects of . . .
Activation of cardiac renin-angiotensin system in unstable angina
Authors: Gian Gastone Neri Serneri, Maria Boddi, Loredana Poggesi, Ignazio Simonetti, Mirella Coppo, Maria Letizia Papa, Gian Franco Lisi, Massimo Maccherini, Roberto Becherini, Andrea Boncompagni, Thomas Toscano, Pietro Amedeo Modesti
Journal: Journal of the American College of Cardiology (2001)
Commons committee calls for more choice over home births
Authors: U. Tayal
Journal: BMJ (2003)

A House of Commons committee has criticised UK maternity services as patchy and has urged more trusts to support women who want to give birth at home.

The health select committee published two reports last week, one on inequality in access to maternity services across the United Kingdom and one on choice in maternity services.

The second report urged healthcare trusts to support the option of home births and to provide independent midwives where needed. The committee estimates that up to 10 times as many women would want to give birth at home, if …
Monitoring blood glucose in gestational diabetes
Authors: A Bargiota, R J M Corrall
Journal: BMJ (1997)

Gestational diabetes mellitus is defined as glucose intolerance first detected during pregnancy with reversion to normal after delivery. It is generally considered a consequence of the endocrine changes of pregnancy in women who are genetically predisposed to non-insulin dependent diabetes. Thus, it is associated with a subsequent cumulative incidence of diabetes as high as 60% after 16 years of follow up.1 Since blood glucose concentrations do not have a bimodal distribution, the frequency of gestational diabetes will depend on the arbitrary blood glucose concentration chosen for diagnosis.

The impact of gestational diabetes is similar to that of established diabetes, although the complications are fewer and less severe. However, there is little consensus in the literature concerning the biochemical definition, perceived ill effects, or appropriate treatment. For initial treatment, dietary instruction is …
Bad medicine: restless legs syndrome
Authors: D. Spence
Journal: BMJ (2013)

All roads lead to neurology, today’s repository for the medically unexplained. Consider the rise of partial epilepsy, tremor, sleep disorders, atypical migraine, complex regional pain syndromes, and paraesthesia, for example. These conditions have limited pathological basis, few objective tests, and are based on symptoms that patients report themselves. The truth is that what we really know about the higher functioning of the brain can be written on the back of a large postage stamp.⇑

Restless legs syndrome (RLS) is deemed a common and serious neurological syndrome that affects 10% of the population,1 with 2-3% …
A primary microcephaly protein complex forms a ring around parental centrioles
Authors: Joo-Hee Sir, Alexis R Barr, Adeline K Nicholas, Ofelia P Carvalho, Maryam Khurshid, Alex Sossick, Stefanie Reichelt, Clive D'Santos, C Geoffrey Woods, Fanni Gergely
Journal: Nature Genetics (2011)