tbuckley/cabot-search huggingface dataset:
Do exogenous oestrogens and progesterone influence asthma?
Authors: L. Forbes
Journal: Thorax (1999)

Between 20% and 40% of women of child- bearing age in the UK use hormonal contraceptives.1 2 In a survey carried out in Oxfordshire in 1990 about 20% of women aged 45–64 years were taking hormone replacement therapy (HRT).3Around 5% of women of childbearing age in the UK have diagnosed asthma, and a higher proportion have asthma-like symptoms.4 There is less information available about the prevalence of asthma in older women, but there is little doubt that it is a common problem in this age group also.

There are no special guidelines on the prescription of hormonal contraceptives or hormone replacement therapy to women with asthma. Should we be concerned about the effect of oestrogens and progesterone on the risk of developing asthma? Should women with asthma avoid hormonal contraceptives and HRT? Or could they have a therapeutic role? The prevalence of asthma and asthma-like symptoms is similar in adult men and women4 but women have a higher risk of hospital admission for asthma than men.5 While this may be due to differences in illness behaviour and thresholds for admission, it may be that women have more severe symptoms, which could be due to their endogenous or exogenous levels of sex hormones. A recent paper documented the rise in asthma prevalence over the last 30 years and noted the parallel increase in the use of the oral contraceptive pill, hypothesising that hormonal contraceptives might increase the risk of asthma in subsequently born children.6 Could they also influence the risk of asthma in women themselves? A body of research that has attempted to explore the influence of exogenous oestrogen and progesterone on the incidence and severity of asthma is reviewed here.

There are theoretical reasons why oestrogens and progesterone might be expected to influence …
Anti–Interleukin-12 Antibody for Active Crohn's Disease
Authors: Peter J. Mannon, Ivan J. Fuss, Lloyd Mayer, Charles O. Elson, William J. Sandborn, Daniel Present, Ben Dolin, Nancy Goodman, Catherine Groden, Ronald L. Hornung, Martha Quezado, Markus F. Neurath, Jochen Salfeld, Geertruida M. Veldman, Ullrich Schwertschlag, Warren Strober
Journal: New England Journal of Medicine (2004)

Crohn's disease is associated with excess cytokine activity mediated by type 1 helper T (Th1) cells. Interleukin-12 is a key cytokine that initiates Th1-mediated inflammatory responses.This double-blind trial evaluated the safety and efficacy of a human monoclonal antibody against interleukin-12 (anti-interleukin-12) in 79 patients with active Crohn's disease. Patients were randomly assigned to receive seven weekly subcutaneous injections of 1 mg or 3 mg of anti-interleukin-12 per kilogram of body weight or placebo, with either a four-week interval between the first and second injection (Cohort 1) or no interruption between the two injections (Cohort 2). Safety was the primary end point, and the rates of clinical response (defined by a reduction in the score for the Crohn's Disease Activity Index [CDAI] of at least 100 points) and remission (defined by a CDAI score of 150 or less) were secondary end points.Seven weeks of uninterrupted treatment with 3 mg of anti-interleukin-12 per kilogram resulted in higher response rates than did placebo administration (75 percent vs. 25 percent, P=0.03). At 18 weeks of follow-up, the difference in response rates was no longer significant (69 percent vs. 25 percent, P=0.08). Differences in remission rates between the group given 3 mg of anti-interleukin-12 per kilogram and the placebo group in Cohort 2 were not significant at either the end of treatment or the end of follow-up (38 percent and 0 percent, respectively, at both times; P=0.07). There were no significant differences in response rates among the groups in Cohort 1. The rates of adverse events among patients receiving anti-interleukin-12 were similar to those among patients given placebo, except for a higher rate of local reactions at injection sites in the former group. Decreases in the secretion of interleukin-12, interferon-gamma, and tumor necrosis factor alpha by mononuclear cells of the colonic lamina propria accompanied clinical improvement in patients receiving anti-interleukin-12.Treatment with a monoclonal antibody against interleukin-12 may induce clinical responses and remissions in patients with active Crohn's disease. This treatment is associated with decreases in Th1-mediated inflammatory cytokines at the site of disease.
Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate‐to‐severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2)
Authors: C. Paul, J. Cather, M. Gooderham, Y. Poulin, U. Mrowietz, C. Ferrandiz, J. Crowley, C. Hu, R.M. Stevens, K. Shah, R.M. Day, G. Girolomoni, A.B. Gottlieb
Journal: British Journal of Dermatology (2015)

Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis.ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis.This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast.The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection.Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks.
THE EXPERIMENTAL PRODUCTION OF COMBINATION FORMS OF VIRUS
Authors: George K. Hirst, Tamar Gotlieb
Journal: The Journal of Experimental Medicine (1953)

The fact that the hemagglutination inhibition test will not detect more than one component in an artificial mixture of two antigenically distinct strains of virus was demonstrated experimentally. With this proved, the inference seemed justified that the inhibition of the hemagglutinin of a virus suspension by each of two antisera, specific for differing strains of virus, would be an indication that some of the specific antigenic components from each of these viruses were both present in single particles of the virus suspension. Two pair of influenza A strains were used to simultaneously inoculate the allantoic sac, and some embryos thus infected yielded virus which had its hemagglutinin inhibited by sera specific against each of the parent forms. Such doubly inhibitable hemagglutinin contributed as much as 84 per cent of the total hemagglutinin in certain fluids. Each of the specific antisera inhibited the hemagglutinin of the combination form very nearly as well as it inhibited its own hemagglutinin.
Reassurance Against Future Risk of Precancer and Cancer Conferred by a Negative Human Papillomavirus Test
Authors: J. C. Gage, M. Schiffman, H. A. Katki, P. E. Castle, B. Fetterman, N. Wentzensen, N. E. Poitras, T. Lorey, L. C. Cheung, W. K. Kinney
Journal: JNCI Journal of the National Cancer Institute (2014)

Primary human papillomavirus (HPV) testing (without concurrent Pap tests) every 3 years is under consideration in the United States as an alternative to the two recommended cervical cancer screening strategies: primary Pap testing every 3 years, or concurrent Pap and HPV testing ("cotesting") every 5 years. Using logistic regression and Weibull survival models, we estimated and compared risks of cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) for the three strategies among 1011092 women aged 30 to 64 years testing HPV-negative and/or Pap-negative in routine screening at Kaiser Permanente Northern California since 2003. All statistical tests were two sided. Three-year risks following an HPV-negative result were lower than 3-year risks following a Pap-negative result (CIN3+ = 0.069% vs 0.19%, P < .0001; Cancer = 0.011% vs 0.020%, P < .0001) and 5-year risks following an HPV-negative/Pap-negative cotest (CIN3+ = 0.069% vs 0.11%, P < .0001; Cancer = 0.011% vs 0.014%, P = .21). These findings suggest that primary HPV testing merits consideration as another alternative for cervical screening.
Atorvastatin Attenuates Remnant Lipoprotein-Induced Monocyte Adhesion to Vascular Endothelium Under Flow Conditions
Authors: Akio Kawakami, Akira Tanaka, Katsuyuki Nakajima, Kentaro Shimokado, Masayuki Yoshida
Journal: Circulation Research (2002)

Remnant lipoproteins have been reported to play a causative role in atherogenesis. We investigated the effect of remnant-like lipoprotein particles (RLPs) on monocyte-endothelial interaction and their potential regulation by atorvastatin. Monocytic U937 cells were incubated with RLPs isolated from hypertriglyceridemia subjects and their adhesion to human umbilical vein endothelial cells (HUVECs) was examined under flow conditions. Incubation of U937 cells with 15 micro g protein/mL RLPs increased their adhesion to HUVECs activated with IL-1beta (untreated: 6.8+/-1.6 cells/HPF versus RLPs: 16.2+/-3.3 cells/HPF, P<0.05). Flow cytometric analysis revealed that incubation with RLPs increased expression levels of CD11a, CD18, and CD49d in U937 cells. Moreover, RLP-induced RhoA activation as well as FAK activation was seen in U937 cells, and RLP-induced RhoA activation seemed to be involved with PKC-dependent signaling. To explore the effect of atorvastatin on RLP-induced U937 cell adhesion to HUVECs, U937 cells were incubated with RLPs in the presence of atorvastatin. Pretreatment of U937 cells with 10 micro mol/L atorvastatin significantly decreased RLP-induced U937 cell adhesion to activated HUVECs (RLP 15.2+/-1.5 cells/HPF versus atorvastatin+RLP 10.2+/-1.0 cells/HPF; P<0.05) and decreased the enhanced integrin expression in RLP-treated U937 cells. Atorvastatin also inhibited RLP-induced RhoA activation and FAK activation in U937 cells. In summary, RLPs induced monocyte adhesion to vascular endothelium by sequential activation of PKC, RhoA, FAK, and integrins, indicating a role of remnant lipoproteins in vascular inflammation during atherogenesis. Atorvastatin attenuated this enhanced monocyte adhesion to HUVECs, suggesting an antiinflammatory role for this compound.
Variations in Hospice Use Among Cancer Patients
Authors: Nancy L. Keating, Lisa J. Herrinton, Alan M. Zaslavsky, Liyan Liu, John Z. Ayanian
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Previous studies have documented that hospice enrollment by terminally ill cancer patients varies substantially by patient characteristics and across broad geographic regions, but little is known about how local practice patterns and individual physicians contribute to these variations. We examined hospice use within a regional integrated health care delivery system that provides consistent insurance coverage and hospice availability for its members to evaluate the relative importance of patient characteristics, physician characteristics, individual physicians, and local health centers in explaining variations in hospice enrollment. Methods: We examined data for 3805 Kaiser Permanente of Northern California health plan enrollees who were diagnosed with and died of lung, colorectal, breast, or prostate cancer from January 1, 1996, through June 30, 2001. We used a random-effects linear probability hierarchical model to estimate adjusted hospice enrollment rates and identify factors associated with hospice enrollment. All P values are two-sided. Results: Overall, 65.4% of patients enrolled in hospice care before death. In adjusted analyses, hospice enrollment did not vary by patients' race/ethnicity or marital status (all P >.2) but varied substantially among the 11 health centers where patients were treated (standard deviation [SD] of random effect = 10.0 percentage points, corresponding to an estimated adjusted hospice enrollment rate for two-thirds of centers (2 SDs) ranging from 55% to 75%, P = .02). Hospice enrollment varied less among the 675 individual physicians (SD = 4.6 percentage points; P = .09). Conclusions: Health care within a large integrated delivery system has the potential to eliminate racial and ethnic disparities in hospice use, but substantial variation in hospice use persists among local health centers. Focused efforts to understand how patients, physicians, and hospices interact at the local level are important to ensure equal access to hospice care for all terminally ill cancer patients.
Positioning to get out of meiosis: the asymmetry of division
Authors: S. Brunet, M. H. Verlhac
Journal: Human Reproduction Update (2010)

During meiosis, mammalian oocytes undergo two successive cell divisions without an intermediate replicative phase. This brief period, called 'meiotic maturation', is crucial for the formation of an egg capable of being fertilized and of generating viable and euploid offspring.We review our current knowledge of the cellular and molecular mechanisms that control asymmetry and appear to be shared between mammalian species, as well as the associated misfunctions that impair the formation of functional female gametes.The two successive divisions that comprise mammalian oogenesis are asymmetric. They lead to the formation of small polar bodies and the large and polarized egg. This asymmetry depends upon the dynamic organization of the oocyte cytoskeleton during both divisions. During meiosis I, microfilaments and associated molecules ensure the targeting of the microtubule spindle at the oocyte periphery. During meiosis II, they anchor the spindle under the plasma membrane. In parallel, the cortex overhanging the spindle is dramatically reorganized. Establishment and maintenance of this cortical domain are crucial for the completion of fertilization. Loss of this differentiated area is characteristic of ageing or low-quality gametes and associated with increased maternal age or post-ovulatory ageing.
Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance
Authors: Ton van Agthoven, Anieta M. Sieuwerts, Marion E. Meijer-van Gelder, Maxime P. Look, Marcel Smid, Jos Veldscholte, Stefan Sleijfer, John A. Foekens, Lambert C.J. Dorssers
Journal: Journal of Clinical Oncology (2008)

Purpose We have previously identified a set of breast cancer antiestrogen resistance (BCAR) genes causing estrogen independence and tamoxifen resistance in vitro using a functional genetic screen. Here, we explored whether these BCAR genes provide predictive value for tamoxifen resistance and prognostic information for tumor aggressiveness in breast cancer patients. Patients and Methods mRNA levels of 10 BCAR genes (AKT1, AKT2, BCAR1, BCAR3, EGFR, ERBB2, GRB7, SRC, TLE3, and TRERF1) were measured in estrogen receptor–positive breast tumors using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with progression-free survival (PFS) in 242 patients receiving tamoxifen as first-line monotherapy for recurrent disease, and with distant metastasis-free survival (MFS) in 413 lymph node-negative (LNN) primary breast cancer patients who did not receive systemic adjuvant therapy. Results Concerning tamoxifen resistance, BCAR3, ERBB2, GRB7, and TLE3 mRNA levels were predictive for PFS, independent of traditional predictive factors. By combining GRB7 (or ERBB2) and TLE3 mRNA levels, patients could be classified in three subgroups with distinct PFS. For the evaluation of tumor aggressiveness, AKT2, EGFR, and TRERF1 mRNA levels were all significantly associated with MFS, independent of traditional prognostic factors. Using the combined AKT2 and EGFR mRNA status, four prognostic groups were identified with different MFS outcomes. Conclusion The majority of BCAR genes, which were revealed to confer tamoxifen resistance and estrogen independence in vitro by functional screening, have clinical relevance, and associate with tamoxifen resistance and/or tumor aggressiveness in breast cancer patients.
Mechanism of Recurrent Ischemic Mitral Regurgitation After Annuloplasty
Authors: Judy Hung, Lampros Papakostas, Stephen A. Tahta, Bruce G. Hardy, Bruce A. Bollen, Carlos M. Duran, Robert A. Levine
Journal: Circulation (2004)

Background— Patients who undergo ring annuloplasty for ischemic mitral regurgitation (MR) often have persistent or recurrent MR. This may relate to persistent leaflet tethering from left ventricle (LV) dilatation that is not relieved by ring annuloplasty. Therefore, the purpose of this study was to test the hypothesis that recurrent MR in patients after ring annuloplasty relates to continued LV remodeling. Methods and Results— Serial echoes were reviewed in 30 patients (aged 72±11 years) who showed recurrent MR late (47±27 months) versus early (3.8±5.8 months) after ring annuloplasty for ischemic MR during coronary artery bypass grafting without interval infarction. Patients with intrinsic mitral valve disease were excluded. Echocardiographic measures of MR (vena contracta and jet area/left atrial area) and LV remodeling (LV dimensions, volumes, and sphericity) were assessed at each stage. The degree of MR increased from mild to moderate, on average, from early to late postoperative stages, without significant change in LV ejection fraction. Changes in MR paralleled increases in LV volumes and sphericity index at end-systole and end-diastole. The only independent predictor of late postoperative MR was LV sphericity index at end-systole. Conclusions— Recurrent MR late after ring annuloplasty is associated with continued LV remodeling, emphasizing its dynamic relation to the LV.
STUDIES ON THE RELATIONSHIP OF CERTAIN VARIANTS OF B. TYPHOSUS
Authors: Francis B. Grinnell
Journal: The Journal of Experimental Medicine (1931)

The results of cross-agglutination and agglutinin absorption experiments with the motile smooth, non-motile smooth, motile rough, and non-motile rough forms of B. typhosus are presented. Cross-agglutination between these four forms is complete, save that the motile rough antigen is under certain conditions only weakly agglutinated by the antisera prepared with the non-motile forms. Cross-absorption of the somatic agglutinogen of the four variants is complete, save that the motile smooth culture still shows granular agglutination with the anti-MS and anti-MR sera after absorption with these cultures. A theory of the antigenic composition of the four variants of B. typhosus is presented, based on the results obtained in these experiments. It would appear that, contrary to the usually accepted theory, the four variants have a common somatic agglutinogen. To explain the difference between the smooth virulent forms and the rough non-virulent forms it has been assumed that the S forms contain a carbohydrate which is associated with virulence and which takes no part in the agglutination reaction.
Delta Hepatitis in the Los Angeles Area: A Report of 126 Cases
Authors: KEVIN M. DE COCK
Journal: Annals of Internal Medicine (1986)

We describe the clinical course in 126 patients with delta hepatitis who have been evaluated in Los Angeles since 1967. In approximately two thirds of all patients, delta infection was associated with chronic hepatitis B. Most patients were members of two major risk groups: 65.9% were intravenous drug abusers, 11.9% were male homosexuals, and another 9.5% were both intravenous drug users and male homosexuals. The overall case fatality rate was 23%; fulminant hepatitis caused 17 of 29 (59%) deaths. Advanced liver disease occurred significantly more frequently in patients who had established chronic delta infections than in hepatitis B virus carriers with recent delta superinfections. Nonfatal infections with both hepatitis B virus and delta hepatitis virus resulted in clearance of both agents, whereas superinfection in carriers of chronic hepatitis B virus usually led to chronic delta hepatitis. Spontaneous loss of chronic delta infection was not observed. Delta hepatitis, a longstanding infection seen in patients in the Los Angeles area, has caused fulminant hepatitis and progressive liver disease in both intravenous drug users and male homosexuals.
The canonical Wnt signalling pathway and its APC partner in colon cancer development
Authors: J. Schneikert, J. Behrens
Journal: Gut (2006)

he flat surface of the colon is covered by an epithelium composed of four differentiated cell types (enterocytes, enteroendocrine, goblet and Paneth cells) that invaginates at regular intervals to form crypts (fig 1).The bottom of the crypts is occupied by a few stem cells that give rise to actively dividing precursor cells that populate the bottom two-thirds of the crypts. 1 Proliferation occurs under the influence of growth factors from the Wnt family that may be produced by the underlying stromal cells underneath the stem cell compartment or by the epithelial cells themselves.The precursors migrate upward in an ordered fashion, which is also controlled by Wnt factors, 2 and they stop proliferation when they reach the top third of the crypt, probably because they are too far from the Wnt source.Meanwhile, they continue their migration movement and colonise the surface of the colon.After about a week, epithelial cells undergo apoptosis and are shed in the lumen of the gut.The Paneth cells constitute an exception, as they migrate downward and occupy the very bottom of the crypt.Thus, the epithelium of the colon is under perpetual renewal.Wnt growth factors activate a cascade of intracellular events, which is known as the canonical Wnt pathway that ultimately leads to the expression of a genetic program controlling the co-ordinated expansion, fate and sorting of the epithelial cell population.In colorectal cancer, epithelial cells initially proliferate inappropriately because they acquired mutations in components of the pathway, thereby mimicking the effect of a permanent Wnt stimulation.Thus, the mutated cell recapitulates a progenitor-like phenotype, independent of its position in the epithelium. 3Canonical Wnt signalling has received considerable attention from cancer researchers over the years, because of its essential role in the homeostasis of the colonic epithelium and its deregulation in colorectal cancer and other tumours.This review attempts to summarise briefly our current understanding of the pathway in relation to its role in colorectal cancer development and to introduce how current knowledge may be used for the development of new treatments against this disease.