tbuckley/cabot-search huggingface dataset:
Human Papillomavirus-Associated Cancers in Patients With Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome
Authors: M. Frisch
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Human papillomavirus (HPV)-associated anogenital malignancies occur frequently in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). The purpose of our study was to determine if the high frequency of these cancers is due to lifestyle factors associated with both HPV and HIV infections or to immunosuppression following HIV infection. Methods: We studied invasive and in situ HPV-associated cancers among 309 365 U.S. patients with HIV infection/AIDS (257 605 males and 51 760 females) from 5 years before the date of AIDS onset to 5 years after this date. Sex-, race-, and age-standardized ratios of observed-to-expected cancers served as measures of relative risk (RR). Trend tests were used to evaluate changes in the RRs during the 10 years spanning AIDS onset. All statistical tests were two-sided. Results: All HPV-associated cancers in AIDS patients occurred in statistically significant excess compared with the expected numbers of cancers. For in situ cancers, overall risks were significantly increased for cervical (RR = 4.6; 95% confidence interval [CI] = 4.3–5.0), vulvar/vaginal (RR = 3.9; 95% CI = 2.0–7.0), anal (in females, RR = 7.8 [95% CI = 0.2–43.6]; in males, RR = 60.1 [95% CI = 49.2–72.7]), and penile (RR = 6.9; 95% CI = 4.2–10.6) cancers, and RRs increased during the 10 years spanning AIDS onset for carcinomas in situ of the cervix (P for trend <.001), vulva/vagina (P for trend = .04), and penis (P for trend = .04). For invasive cancers, overall risks were significantly increased for cervical (RR = 5.4; 95% CI = 3.9–7.2), vulvar/vaginal (RR = 5.8; 95% CI = 3.0–10.2), and anal (RR = 6.8; 95% CI = 2.7–14.0) cancers in females and for anal (RR = 37.9; 95% CI = 33.0–43.4), penile (RR = 3.7; 95% CI = 2.0–6.2), tonsillar (RR = 2.6; 95% CI = 1.8–3.8), and conjunctival (RR = 14.6; 95% CI = 5.8–30.0) cancers in males. However, RRs for invasive cancers changed little during the 10 years spanning AIDS onset. Conclusions: HPV-associated malignancies occur at increased rates in persons with HIV/AIDS. Increasing RRs for in situ cancers to and beyond the time of AIDS onset may reflect the gradual loss of control over HPV-infected keratinocytes with advancing immunosuppression. However, the lack of a similar increase for invasive HPV-associated cancers suggests that late-stage cancer invasion is not greatly influenced by immune status.
PREDICTIVE VALUE OF IN VITRO MODEL SYSTEMS IN TOXICOLOGY
Authors: Julio C. Davila, Rosita J. Rodriguez, Russell B. Melchert, Daniel Acosta
Journal: The Annual Review of Pharmacology and Toxicology (1998)

▪ Abstract The application of in vitro model systems to evaluate the toxicity of xenobiotics has significantly enhanced our understanding of drug- and chemical-induced target toxicity. From a scientific perspective, there are several reasons for the popularity of in vitro model systems. From the public perspective, in vitro model systems enjoy increasing popularity because their application may allow a reduction in the number of live animals employed in toxicity testing. In this review, we present an overview of the use of in vitro model systems to investigate target organ toxicity of drugs and chemicals, and provide selective examples of these model systems to better understand cutaneous and ocular toxicity and the role of drug metabolism in the hepatotoxicity of selected agents. We conclude by examining the value and use of in vitro model systems in industrial development of new pharmaceutical agents.
ROS signalling between endothelial cells and cardiac cells
Authors: M. Zhang, A. M. Shah
Journal: Cardiovascular Research (2014)

The heart contains not only cardiomyocytes but also other cell types such as endothelial cells and fibroblasts. Functional crosstalk among these cell types is important for normal cardiac function and is also involved in disease pathophysiology. Recent data indicate that redox signalling within and between endothelial cells and cardiomyocytes, both through direct and indirect mechanisms, is an important aspect of the functional communication between these cell types. Such signalling influences contractile function, cardiomyocyte growth, hypertrophy, angiogenesis, and fibrosis, and may play an important role in cardiac remodelling in disease.
Good tidings for postlaryngectomy speech
Authors: Milan Eorcok
Journal: JAMA (1982)

Although there have been many advances in rehabilitation of the voice following laryngectomy, the physical effort involved in speaking and the inconvenience of having to occlude the tracheostoma manually during speech has continued to disturb postlaryngectomy patients. Now a new tracheostoma valve that opens and closes automatically, in response to expiratory airflow, and a new lowpressure voice prosthesis that generates airflow resistance similar to that of the human larynx may alleviate some of these problems. In a presentation at the recent meeting of the American Broncho-Esophagological Association in Palm Beach, Fla, speech pathologist Eric D. Blom, PhD, and head and neck surgeon Mark I. Singer, MD, of Indianapolis, reported on the new ease of speech experinced by patients fitted with the "no-hands" Blom-Singer tracheostoma valve and the low-pressure prosthesis. "They feel now like they're really talking," Bloom and Singer told<i>JAMA</i>MEDICAL NEWS. "They can tell immediately the significant reduction
Corticosteroid treatment and prognosis in pulmonary eosinophilia.
Authors: S Capewell, B J Chapman, F Alexander, A P Greening, G K Crompton
Journal: Thorax (1989)

The acute and long term responses to corticosteroid treatment in 65 patients with pulmonary eosinophilia have been reviewed. Of the 247 episodes of pulmonary eosinophilia that were documented during a median follow up period of 14 years, 186 were treated with prednisolone. Complete clearing of chest radiographic infiltrates occurred in 65% of the 247 episodes, partial clearing in 25%, and no response in 9%. Blood eosinophil counts were monitored during 194 episodes and returned to normal in 72%, decreased in 19%, and remained raised in 9%. Complete radiological clearing and a reduction in blood eosinophil counts were more common in episodes treated with prednisolone. Long term prednisolone was given to 28 of the 33 patients with allergic bronchopulmonary aspergillosis (mean 7.4 mg/day for 11 years) and to 29 of the 32 "non-aspergillosis" patients (mean 8.1 mg/day for 4.6 years). Initial pulmonary function, measured between episodes, was worse in patients with allergic aspergillosis than in those without (mean % predicted: FEV1 57% v 83%, vital capacity (VC) 76% v 88%). During a mean follow up period of 12 years neither group displayed further decline in FEV1 or VC.
Sex and the subgingival microbiome: Do female sex steroids affect periodontal bacteria?
Authors: Purnima S. Kumar
Journal: Periodontology 2000 (2012)

Abstract Fluctuations in the levels of sex steroid hormones begin at menarche and end with menopause in the human female. The association between gingivitis and increases in systemic sex steroids has been extensively reported and the biological mechanisms underlying this florid inflammatory state have been examined over several decades. The purpose of this review is to critically examine the evidence in the literature on the effect of female sex steroids on oral bacterial communities.
Down-regulation of Gfi-1 expression by TGF-β is important for differentiation of Th17 and CD103+ inducible regulatory T cells
Authors: Jinfang Zhu, Todd S. Davidson, Gang Wei, Dragana Jankovic, Kairong Cui, Dustin E. Schones, Liying Guo, Keji Zhao, Ethan M. Shevach, William E. Paul
Journal: The Journal of Experimental Medicine (2009)

Growth factor independent 1 (Gfi-1), a transcriptional repressor, is transiently induced during T cell activation. Interleukin (IL) 4 further induces Gfi-1, resulting in optimal Th2 cell expansion. We report a second important function of Gfi-1 in CD4 T cells: prevention of alternative differentiation by Th2 cells, and inhibition of differentiation of naive CD4 T cells to either Th17 or inducible regulatory T (iTreg) cells. In Gfi1−/− Th2 cells, the Rorc, Il23r, and Cd103 loci showed histone 3 lysine 4 trimethylation modifications that were lacking in wild-type Th2 cells, implying that Gfi-1 is critical for epigenetic regulation of Th17 and iTreg cell–related genes in Th2 cells. Enforced Gfi-1 expression inhibited IL-17 production and iTreg cell differentiation. Furthermore, a key inducer of both Th17 and iTreg cell differentiation, transforming growth factor β, repressed Gfi-1 expression, implying a reciprocal negative regulation of CD4 T cell fate determination. Chromatin immunoprecipitation showed direct binding of the Gfi-1–lysine-specific demethylase 1 repressive complex to the intergenic region of Il17a/Il17f loci and to intron 1 of Cd103. T cell–specific Gfi1 conditional knockout mice displayed a striking delay in the onset of experimental allergic encephalitis correlated with a dramatic increase of Foxp3+CD103+ CD4 T cells. Thus, Gfi-1 plays a critical role both in enhancing Th2 cell expansion and in repressing induction of Th17 and CD103+ iTreg cells.
Synthesis and Degradation of Hyaluronic Acid in the Cultured Fibroblasts of Marfan's Disease
Authors: Stanford I. Lamberg, Albert Dorfman
Journal: Journal of Clinical Investigation (1973)

Increased amounts of hyaluronic acid accumulate in fibroblasts cultured from patients with Marfan's disease, an autosomal dominant disorder. In the recessive Hurler's disease, the storage of glycosaminoglycan (GAG) is due to impaired degradation. This study examines the kinetics of GAG accumulation in Marfan's disease in order to determine whether the mechanism of accumulation differs from that in Hurler's disease.Marfan-derived fibroblasts incorporated [(14)C]acetate or [(14)C]glucosamine into GAG to a level 4-6 times greater than control fibroblasts. Sugar analyses, electrophoretic mobility, and enzyme susceptibility studies showed that the isolated material was hyaluronic acid. There were no differences in activity of a variety of glycosidases between Marfan and control fibroblasts, nor were there differences in the ability to degrade prelabeled hyaluronate by cell-free extracts. Finally, chase experiments showed parallel rates of loss of labeled GAG from control fibroblasts and fibroblasts from Marfan patients. It appears that hyaluronic acid was accumulating in greater amounts in the fibroblasts from patients with Marfan's disease because of a greater rate of synthesis as opposed to a decreased rate of breakdown.
Results from systematic screening for cardiovascular risk in outpatients with rheumatoid arthritis in accordance with the EULAR recommendations
Authors: Jette Primdahl, Joan Clausen, Kim Hørslev-Petersen
Journal: Annals of the Rheumatic Diseases (2013)

To investigate risk factors for the development of cardiovascular disease (CVD) and estimate the risk of cardiovascular death in rheumatoid arthritis (RA) patients in accordance with EULAR recommendations.Outpatients with RA ≤85 years of age from a Danish hospital were invited to participate. Patients' risk of cardiovascular death was calculated according to the SCORE system, based on total cholesterol/high-density lipoprotein (HDL) ratio, smoking habits, blood pressure, age and gender. The SCORE was adjusted based on disease duration, IgM-RF/anti-CCP positivity and the presence of extra-articular manifestations. Factors such as history of CVD, hypertension or diabetes mellitus (DM), fasting glucose, exercise habits, body mass index (BMI) and waist circumference were explored.836 patients participated; 71.5% women; mean (SD) age 64.3 years (12.0); 152 (19.1%) were already diagnosed with CVD and 74 (9.0%) with DM. Among the 644 patients without CVD or DM, 158 (24.5%) were smokers, 229 (35.8%) had a systolic blood pressure ≥140, 397 (65.6%) total cholesterol ≥5.0 mM/L, 326 (55.4%) low-density lipoprotein cholesterol ≥3.0 mM/L, 18 (4.0%) women and 19 (12.1%) men had a HDL-cholesterol level below 1.2/1.0 mM/L. BMI was >25 in 409 (63.8%). Waist circumference was above 80/94 cm in 297 (63.3%) of female and 111 (63.8%) of male patients, respectively, and 418 (64.9%) exercised ≤5 times a week. Among patients without DM, 14.3% had a fasting glucose ≥6.0 mmol/L. The SCORE was ≥5 in 122 (20.2%). They were referred to follow-up by their GP and community advice services.Systematic screening revealed several risk factors that needed medical follow-up or support to initiate lifestyle changes.
Progress in cystic fibrosis and the CF Therapeutics Development Network
Authors: Steven M Rowe, Drucy S Borowitz, Jane L Burns, John P Clancy, Scott H Donaldson, George Retsch-Bogart, Scott D Sagel, Bonnie W Ramsey
Journal: Thorax (2012)

Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised.
Antacid provides better restoration of glandular structures within the gastric ulcer scar than omeprazole.
Authors: A Schmassmann, A Tarnawski, H A Gerber, B Flogerzi, M Sanner, L Varga, F Halter
Journal: Gut (1994)

Mucosa of healed gastric ulcers displays histological abnormalities that are possibly the basis of ulcer recurrence. The influence of antacid and omeprazole treatment was studied on the quality of ulcer healing. Sixty four rats with gastric cryoulcers were treated daily either with placebo, antacid, omeprazole, or antacid plus omeprazole. Ulcer size was measured three times per week with a novel video endoscopic method. Prostaglandin generation (day 6), cell proliferation (day 8 and 15), height and cell composition of ulcer margin (day 8), and mucosal scar (day 15) were quantitatively assessed. Antacid, omeprazole, and antacid plus omeprazole significantly accelerated ulcer healing predominantly during days 3-8. Compared with placebo, the height of ulcer margin and mucosal ulcer scar was significantly increased in antacid (+7 and +9% respectively) and significantly decreased in omeprazole (-33 and -22% respectively) and antacid plus omeprazole (-26 and -18% respectively) treated rats. The number of bromodeoxyuridine labelled cells (+42%, day 8), epithelial cell mass (+42%, day 15), and the ratios of epithelial cells/connective tissue (+73%, day 15) and epithelial cells/gland lumen (+100%, day 15) were significantly increased in antacid treated rats. In conclusion, both antacid and omeprazole accelerate ulcer healing but antacid provides a better quality of healing. This advantage is lost by cotreatment with omeprazole.
Cyclin D1, p53, and p21Waf1/Cip1 Expression Is Predictive of Poor Clinical Outcome in Serous Epithelial Ovarian Cancer
Authors: Anish Bali, Philippa M. O’Brien, Lyndal S. Edwards, Robert L. Sutherland, Neville F. Hacker, Susan M. Henshall
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Dysregulation of cell cycle control, in particular G1-S-phase transition, is implicated in the pathogenesis of most human cancers, including epithelial ovarian cancer (EOC). However, the prognostic significance of aberrant cell cycle gene expression in EOC remains unclear. Experimental Design: The expression of selected genes from the pRb pathway that regulates G1-S-phase progression, including cyclin D1, p16Ink4a, cyclin E, p27Kip1, p21Waf1/Cip1, and p53, was examined in a consecutive series of 134 serous EOC using immunohistochemistry and the results correlated to disease outcome. Results: Molecular markers predictive of reduced overall survival in univariate analysis were overexpression of cyclin D1 (P = 0.03) and p53 (P = 0.03) and reduced expression of p27Kip1 (P = 0.05) and p21Waf1/Cip1 (P = 0.02), with the latter three also being prognostic for a shorter progression-free interval. In addition, patients displaying overexpression of p53 with concurrent loss of p21Waf1/Cip1 had a significantly shorter overall (P = 0.0008) and progression-free survival (P = 0.0001). On multivariate analysis, overexpression of cyclin D1 and combined loss of p21Waf1/Cip1 in the presence of p53 overexpression were independent predictors of overall survival. Similarly, the combination of p21Waf1/Cip1 loss and p53 overexpression was independently predictive of a shorter progression-free interval. Overexpression of p53 and cyclin E and reduced expression of p27Kip1 and p21Waf1/Cip1 were significantly associated with increasing tumor grade. Conclusions: This study confirms that dysregulation of cell cycle genes is common in EOC, and that aberrant expression of critical cell cycle regulatory proteins can predict patient outcome in serous EOC.
Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells
Authors: Tim Worbs, Ulrike Bode, Sheng Yan, Matthias W. Hoffmann, Gabriele Hintzen, Günter Bernhardt, Reinhold Förster, Oliver Pabst
Journal: The Journal of Experimental Medicine (2006)

Oral tolerance induction is a key feature of intestinal immunity, generating systemic nonresponsiveness to ingested antigens. In this study, we report that orally applied soluble antigens are exclusively recognized in the intestinal immune system, particularly in the mesenteric lymph nodes. Consequently, the initiation of oral tolerance is impeded by mesenteric lymphadenectomy. Small bowel transplantation reveals that mesenteric lymph nodes require afferent lymph to accomplish the recognition of orally applied antigens. Finally, oral tolerance cannot be induced in CCR7-deficient mice that display impaired migration of dendritic cells from the intestine to the mesenteric lymph nodes, suggesting that immunologically relevant antigen is transported in a cell-bound fashion. These results demonstrate that antigen transport via afferent lymphatics into the draining mesenteric lymph nodes is obligatory for oral tolerance induction, inspiring new therapeutic strategies to exploit oral tolerance induction for the prevention and treatment of autoimmune diseases.
Impact of adalimumab on work participation in rheumatoid arthritis: comparison of an open-label extension study and a registry-based control group
Authors: M T Halpern, M A Cifaldi, T K Kvien
Journal: Annals of the Rheumatic Diseases (2008)

Rheumatoid arthritis (RA) causes considerable disability and often results in loss of work capacity and productivity. This study evaluated the impact of adalimumab, a tumour necrosis factor antagonist with demonstrated efficacy in RA, on long-term employment.Data from an open-label extension study (DE033) of 486 RA patients receiving adalimumab monotherapy who previously did not respond to at least one disease-modifying antirheumatic drug (DMARD) and had baseline work status information were compared with data from 747 RA patients receiving DMARD treatment in a Norway-based longitudinal registry. Primary outcomes included the time patients continued working at least part time and the likelihood of stopping work. Secondary outcomes included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) responses and disease remission. Outcomes were compared 6, 12 and 24 months after enrolment.During a 24-month period, the 158 patients who received adalimumab and were working at baseline worked 7.32 months longer (95% CI 4.8 to 9.1) than did the 180 patients treated with DMARDs, controlling for differences in baseline characteristics. Regardless of baseline work status, patients receiving adalimumab worked 2.0 months longer (95% CI 1.3 to 2.6) and were significantly less likely to stop working than those receiving DMARDs (HR 0.36 (95% CI -0.30 to 0.42) for all patients and 0.36 (95% CI 0.15 to 0.85) for patients working at baseline, respectively). The patients who received adalimumab were also considerably more likely to achieve ACR responses and disease remission than DMARD-treated patients. Patients who achieved EULAR good response and remission were less likely to stop working, but this relationship was only seen in patients receiving DMARDs.Patients with RA who received adalimumab experienced considerably longer periods of work and continuous employment, and greater rates of clinical responses, than patients receiving DMARDs. The mechanism by which adalimumab decreases likelihood of stopping work seems to be different from that of DMARD treatment and independent of clinical responses.
The Position of the Mammalian Limb, Regarded in the Light of its Innervation and Development
Authors: A. M. Paterson
Journal: BMJ (1888)

tain point advantageous to the individual in performing his par- ticular form of labour.When the normal mechanical condition of the body is altered, the transmission of the body weight alone may be.sufficient to produce ossification of the ligaments, which sustain an abnormal amount of weight habitually.For instance, in more than one well-marked example of dorsal excurvation acquired early in life, I have found a good-sized piece of bone in the hypertrophied liga- mentum nuchae, as well as considerable prominence of the bony attachment of that ligament to the occiput.
P256 Investigating suspected pulmonary embolism as outpatient: the Portsmouth experience
Authors: I. Shafiq, N. Siddique, A. J. Chauhan, L. Albon, V. King, S. R. Alapati
Journal: Thorax (2010)

Introduction Suspected PE is a commonacute medical presentation. It continues to be a significant burden on the healthcare resources, hence it makes sense to investigate and manage stable patients with suspected PE as outpatient. There is very limited evidence available on the safety of investigation of PE as outpatient. The aim of this study was to review the outcomes of investigation for PE on outpatient basis. Methods During 6 months period from November 2007 to April 2008, 176 patients were investigated for suspected pulmonary embolism as outpatient, based on clinical criteria of stability (eg notachycardia, tachypnea or hypotension). All of these patients were treated withenoxaparin from the day of admission till the diagnosis of PE was confirmed or excluded. We randomly selected 92 of these patients and retrospectively reviewed their clinical notes. The data recorded included pulse, blood pressure, respiratory rate, PO2, PCO2, Trop t and D.dimer. We also looked at the number of days patients had to wait for the CTPA or VQ scan. All patients were reviewed in clinic after a VQ scan or CTPA. Results 12 out of 91 (13.2%) patients were diagnosed with PE. There were no deaths and no significant complications recorded from either PE or enoxaparin therapy. Average time taken for PE to be diagnosed or excluded was 3.86 days. There were no significant differences in clinical or physiological parameters between groups apart from PO2, which was significantly lower in the group with PE (p 0.032) ([Abstract P256 Table 1][1]). View this table: Conclusions We conclude from this small series that it may be safe to investigate suspected PE as outpatient in selected clinically stable patients, though this needs to be confirmed in larger studies with an evaluation of health economic benefits. [1]: #T1