tbuckley/cabot-search huggingface dataset:
Predictors of delayed sputum culture conversion in tuberculosis patients
Authors: Patrícia Caetano Mota, Aurora Carvalho, Isabel Valente, Rosário Braga, Raquel Duarte
Journal: European Respiratory Journal (2011)

Introduction:  Failure to sputum culture conversion at the second month of tuberculosis (TB) treatment has been reported to be a predictor of patient infectivity and treatment failure.   Aim:  To identify factors associated with delayed sputum culture conversion among pulmonary TB patients under anti-TB treatment.   Methods:  Retrospective cohort of 136 adult patients with culture-proven pulmonary TB referred to an urban Chest Disease Centre (January 2006-June 2009). Delayed sputum culture conversion was defined as persistent culture positivity after 2 months of treatment. Socio-demographic, clinical, radiological, microbiological, and therapeutic data were evaluated. Univariate and multivariate logistic regression analyses were performed.   Results:  Mean age was 43.3 (± 13.8) years; 75.0% were male. Median sputum culture conversion time was 46 days. Delayed sputum culture conversion was found in 27.2% (n=37) of patients. In univariate analysis, unemployment (38.0% vs 20.9%, p=0.031), HIV positivity (53.3% vs 24.0%, p=0.028), bilateral radiological involvement (42.0% vs 19.0%, p=0.005), cavitary disease (32.6% vs 15.9%, p=0.041), and colony counts ≥ 100 (33.7% vs 8.7%, p=0.018) were risk factors for persistent positive culture. In multivariate logistic regression analysis, only bilateral radiological involvement (odds ratio (OR) 3.7, 95% confidence interval (CI): 1.5–9.0) and higher colony counts (OR 5.8, 95% CI: 1.2–27.4) were independently associated with delayed sputum culture conversion.   Conclusions:  Delayed sputum culture conversion was found in approximately one third of patients. Bilateral radiological involvement and higher colony counts were independent risk factors for delayed sputum culture conversion.
Phase Ii Study of Carboplatin/Etoposide Plus Ly2510924, a Cxcr4 Peptide Antagonist, Versus Carboplatin/Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer (Sclc)
Authors: D.R. Spigel, R.W. Weaver, M. McCleod, O. Hamid, J.R. Stille, J. Polzer, S. Roberson, R. Salgia
Journal: Annals of Oncology (2014)
Uterus of Rodents as Site for Manifestation of Transplantation Immunity Against Transplantable Tumors&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Michael Schlesinger
Journal: JNCI Journal of the National Cancer Institute (1962)

Tumor homografts in uterine horns of mice and rats were studied to see whether the maintenance of pregnancy depended on peculiar properties of the uterus that make it a favorahle site for foreign grafts. Grafts of transplantable mouse and rat tumors in uteri of hosts of the strain of origin resulted in a high percentage of takes. Homografts of the strain-specific MMC1A and the non-strain-specific MC1A transplantable tumors in uteri of mice of foreign strains resulted in a high percentage of takes 8 days after grafting, but growth of the strain-specific tumor was only transitory. Intrauterine mouse tumor homografts in immunized recipients gave negative results in nonpregnant, pseudopregnant, and unilaterally pregnant mice. Heterografts of mouse tumors in the uteri of nonpregnant or pseudopregnant rats failed to grow. Intrauterine homografts of a rat sarcoma in foreign-strain rats resulted in the same low rate of takes as subcutaneous grafts. It is concluded that the uterine horn is a site at which transplantation immunity can manifest itself. Preliminary data also show that the uterus is a site where homografts can elicit a state of homograft immunity.
Abstract 295: Cardiac-Specific Gene Leucine-Rich Repeat Containing 10 (Lrrc10) is required for proper Cardiac Contractility and Responses to Biomechanical Stress
Authors: Youngsook Lee, Matthew Brody, Li Feng, Courtney Reynolds, Ravi Balijepalli
Journal: Circulation Research (2014)

The molecular genetic basis for early onset dilated cardiomyopathy (DCM) is largely unknown. We have identified that Lrrc10 is a cardiac-specific gene regulated by Nkx2.5 and GATA4. Lrrc10-null (Lrrc10-/-) mice exhibit prenatal systolic dysfunction followed by early onset DCM after birth. However, mechanistic roles for LRRC10 in the regulation of cardiac pathophysiology are unknown. We hypothesize that LRRC10 expression is critical for myocyte contractility and proper responses to pressure overload. Various mouse models with pathological cardiac hypertrophy showed decreased levels of Lrrc10. To test roles of LRRC10 in response to biomechanical stress, transverse aortic constriction (TAC) was performed. Lrrc10-/- mice showed significant increases in left ventricular inner diameter dimensions and drastically reduced % fractional shortening in response to 4 weeks of TAC (13%) after 4 weeks, while no significant changes occurred in WT after TAC (26% F.S.). These data indicate that pressure overload greatly exacerbates systolic dysfunction in Lrrc10-/- vs WT hearts. Next, the role of LRRC10 in cardiac excitation contraction coupling was investigated. Myocyte contractility and calcium transients were studied using the video-edge detection system and fura 2-AM loading at basal levels and following perfusion with Isoproterenol (ISO, 10 nM) at 0.5 - 2 Hz pacing. Cell shortening was significantly reduced following perfusion with ISO in Lrrc10-/- myocytes (55% and 49% at 1 and 2 Hz, respectively) vs WT. Calcium transient analysis showed that there were no differences in peak amplitudes of [Ca2+]i between Lrrc10-/- and WT myocytes at baseline or with ISO treatment. Whole-cell voltage clamp experiments demonstrated a significant reduction in the L-type Ca2+ current (ICa,L) density in Lrrc10-/- myocytes (-2.5 ± 0.2 pA/pF) compared to WT myocytes (-6 ± 0.6 pA/pF). The inactivation of the ICa,L in Lrrc10-/- myocytes was significantly delayed. Further, co-immunoprecipitation showed that LRRC10 directly associated with Cav1.2 subunit of LTCC, which correlates well with the localization of LRRC10 to dyadic regions in adult cardiomyocytes by TEM. Therefore, LRRC10 is a novel DCM candidate gene essential for normal myocyte contractility via regulating ICa,L.
Nosocomial urinary tract infection in the intensive care unit: when should Pseudomonas aeruginosa be suspected? Experience of the French national surveillance of nosocomial infections in the intensive care unit, Rea-Raisin
Authors: A.-G. Venier, T. Lavigne, P. Jarno, F. L'heriteau, B. Coignard, A. Savey, A.-M. Rogues
Journal: Clinical Microbiology and Infection (2011)
Phenotypic features in COPD smokers attending a smoking cessation unit
Authors: Carlos A. Jimenez Ruiz, Ana Maria Cicero Guerrero, Maria Luisa Mayayo Ulibarri, Maria Isabel Cristobal Fernandez, Gema Lopez Gonzalez
Journal: European Respiratory Journal (2011)

COPD smokers have specific features of their smoking habit.  We reviewed medical histories of all COPD patients who were treated in our Unit between January 2004 and January 2010.Medical and smoking histories were obtained during the baseline visit, as well as different test results such as FTND-questionnaire, Reward Test and Test to measure psychological, social and gestual dependence.  These test results obtained were compared whit those of a historical group of non-COPD patients treated in our Unit (Control Group).  472 COPD smokers showed the following data for gender (65% were male), average age 58,3 (9,8), number of cigarettes per day 29,7 (13,4), number of years smoking 40,5 (9,9) and number of pack-years 59,1 (30,2). For the control group, which consisted of 1850 patients, these data were 50% male, 47,8 (11), 28,3 (10,4), 32,3 (11,5) and 45,8 (25,7), respectively.  The average score on FTND-questionnaire was 7,4 (2,1) for COPD patients, against 6,5 (2,4), p  COPD patients had a low rate on gestual and social dependence, as well as on automatism. On the contrary, they had a high rate on psychic dependence and sedation.  COPD smokers who attend a smoking cessation unit are generally male over 55 years old, have higher figures of years smoking and higher pack-year figures than the control group. Their physical nicotine dependence is higher than for those in the control group. They are negative reward smokers more often and more significantly than those in the control group.  COPD smokers have a low grade of gestual and social dependence and a high grade of psychic dependence.
Influence of letrozole on plasma estrogen levels in postmenopausal patients with metastatic breast cancer and the effect of estrogen levels on response rates
Authors: J. Zidan, A. Abzah, L. Chetver, W. Basher, J. Shneider, S. Tamam
Journal: Journal of Clinical Oncology (2007)

1078 Background: The aromatase inhibitor (AI) letrozole and other members of this treatment group are very effective in the treatment of postmenopausal women with breast cancer. AIs markedly reduce estrogen levels in postmenopausal women by inhibiting aromatase. At menopause estradiol levels are about 25 pmol/l. Estradiol levels are higher in plasma of women with breast cancer as compared with women with no breast cancer. The purpose of this prospective study is to evaluate estradiol levels before and during letrozole treatment and the effect of primary estradiol levels and their decrease on response rate. Methods: Letrozole 2.5 mg/day orally was given to 50 patients (pts) with metastatic and locally advanced breast cancer (MBC). All pts had measurable disease. Overnight fasting clotted blood samples used for assessment of serum levels of estradiol at baseline and after 3, 6 and 12 months. Estradiol levels were compared to clinical response in this single stage study. Results: Mean age was 56 years (range 46–89 y). Mean years from menopause to starting letrozole was 9 years.12% of pts received previous hormonotherapy and and 30% received chemotherapy for their metastatic disease. Estradiol levels decreased from a mean of 40 pmol/l before letrozole to 40 pmol/l and &lt;40 pmol/l in 19 pts (38%). No difference in estradiol depression rate was found between the 2 groups. In the first group (estradiol &gt;40 pmol/l) objective response rate was 48%: 4 complete responses (CR) and 11 partial responses (PR) out of 31 pts, 12 pts had stabilization of the disease (SD). In the second group 3 pts had CR, 5 had PR: objective response rate of 42% (8/19), and 42% SD. There is a trend (not significant) for higher response rate in pts with higher estradiol levels at the beginning of treatment. Conclusions: Letrozole was found to cause very high estradiol suppression and high response rates in postmenopausal women with advanced breast cancer. A trend was found for higher response rates in pts with higher estradiol levels at baseline although difference was not significant. This is the first study to address this issue. No significant financial relationships to disclose.
Diagnostic value of PET-CT in pleural diseases
Authors: Atila Akkoclu, Kemal Can Tertemiz, Aylin Ozgen Alpaydin, Volkan Karacam
Journal: European Respiratory Journal (2014)

Introduction:Contribution of pleural needle biopsy for diagnosis of pleural effusion differs according to extensiveness of pleural invasion and disease type. We analysed the diagnostic concordance of pleural needle biopsy and VATS biopsy and the correlation between pleural needle biopsy and pathological SUV uptake in PET-CT.

Method: We analysed pleural needle biopsy results of 98 patients retrospectively.

Results: 24 patients were diagnosed as malignant, 62 as benign and 12 as non-diagnostic with pleural needle biopsy. VATS was performed in 48 patients. Comprasion between pleural needle biopsy and VATS biopsy is shown.

View this table:

Table 1





PET-CT was performed for 49 patients and 33 have pathological SUV uptake. Malignancy was diagnosed with pleural needle biopsy in 12 patients, 13 with VATS biopsy and one with open lung biopsy in patients with pathological SUV uptake. Seven patients of 16 with non-pathological SUV uptake have malignancy end diagnosis (6 VATS, one pleural needle biopsy). Most of these patients have metastatic tumours other than lungs. (2 lung cancer,3 lymphoma,colon and breast cancer). Malignancy diagnosis with pleural needle biopsy was significantly higher in patients with pathological SUV uptake (p<0,05).

Pathological SUV uptake and malignancy diagnosis was statisticaly significantly correlated (p<0,05).

Coclusion:Pathological SUV uptake in PET-CT shows malignancy with high rates. Patients suspected from malignancy with non-pathological SUV uptake should be evaluated directly for VATS biopsy due to low diagnostic rates with pleural needle biopsy.
Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection
Authors: Salim Safurdeen. Abdool Karim, Quarraisha. Abdool Karim, Ayesha B. M. Kharsany, Cheryl. Baxter, Anna Christina. Grobler, Lise. Werner, Angela. Kashuba, Leila E. Mansoor, Natasha. Samsunder, Adrian. Mindel, Tanuja N. Gengiah
Journal: New England Journal of Medicine (2015)

Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections.We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2-negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing.The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P=0.005).In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.).
NOX1 to NOX2 switch deactivates AMPK and induces invasive phenotype in colon cancer cells through overexpression of MMP-7
Authors: Suhrid Banskota, Sushil C. Regmi, Jung-Ae Kim
Journal: Molecular Cancer (2015)

Although matrix metalloproteinase (MMP)-7 expression is correlated with increased metastatic potential in human colon cancer cells, the underlying molecular mechanism of invasive phenotype remains unknown. In the current study, we investigated the regulatory effects of membrane NADPH oxidase (NOX) and AMP activated protein kinase (AMPK) on MMP-7 expression and invasive phenotype change in colon cancer cells.Production of superoxide anion was measured by lucigenin chemiluminescence assay using whole cells and protein extracts (NADPH oxidase activity), and intracellular reactive oxygen species (ROS) by fluorescence microscopy using 2',7'-dichlorofluorescein diacetate (DCF-DA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to measure mRNA and protein levels, respectively. siRNA transfection was used to assess involvement of genes in cancer invasion, which were identified by Matrigel transwell invasion assay. Luciferase reporter assay was performed to identify transcription factors linked to gene expression.Under basal conditions, less invasive human colon cancer cells (HT29 and Caco-2) showed low MMP-7 expression but high NOX1 expression and AMPK phosphorylation. Treatment of HT29 and Caco-2 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced an invasive phenotype response along with corresponding increases in ROS production and NOX2 and MMP-7 expression as well as reduced AMPK phosphorylation, which resemble basal conditions of highly invasive human colon cancer cells (SW620 and HCT116). In addition, inverse regulation between AMPK phosphorylation and NOX2 and MMP-7 expression was observed in HT29 cells treated with different concentrations of exogenous hydrogen peroxide. TPA-induced invasive phenotype in HT29 cells was abolished by treatment with Vit. E, DPI, apocynin, and NOX2 siRNA but not NOX1 siRNA, indicating NOX2-derived ROS production induced an invasive phenotype. TPA-induced induction of MMP-7 expression was suppressed by AP-1, NF-κB, and MAPK (ERK, p38, and JNK) inhibitors, whereas TPA-induced expression of NOX2 and its regulators, p47phox and p67phox, was blocked by p38 and NF-κB inhibitors.Molecular switch from NOX1 to NOX2 in colon cancer cells induces ROS production and subsequently enhances MMP-7 expression by deactivating AMPK, which otherwise inhibits stimulus-induced autoregulation of ROS and NOX2 gene expression.
Interference With Tumor Cell-Induced Degradation of Endothelial Matrix on the Antimetastatic Action of Nafazatrom2
Authors: Charles A. Maniglia, Pat P. Loulakis, Alan C. Sartorelli
Journal: JNCI Journal of the National Cancer Institute (1986)

The antithrombotic compound nafazatrom was evaluated in several in vivo and in vitro assays to elucidate the mechanism of its antimetastatic activity. C57BL/6 mice bearing B16 amelanotic subcutaneous tumors treated with 100 mg nafazatrom/kg/day exhibited a sixfold reduction in metastatic pulmonary lesions compared to lesion numbers in controls. The reduction in metastatic lesions was not accompanied by changes in primary tumor growth, and up to 1 microgram nafazatrom/ml did not inhibit tumor cell proliferation in vitro. Treatment of C57BL/6 mice with nafazatrom prior to iv inoculation of tumor cells failed to inhibit lung colony formation. In vitro exposure of exponentially growing B16 amelanotic cells to nafazatrom (1 microgram/ml for 72 hr) in culture did not change their ability to adhere to endothelial cell monolayers. B16 amelanotic cells degraded the matrix material of bovine endothelial cell monolayers; a heparin sulfate proteoglycan appeared to be the predominant matrix component released by these tumor cells, as judged by resistance to chondroitin ABC lyase and sensitivity to heparitinase and pronase degradation. Nafazatrom (1 microgram/ml for 72 hr) inhibited the solubilization of matrix components by approximately 60%. Tumor cell degradation of matrix components is an important event in the pathogenesis of metastasis. Thus the interference with this process appears to provide an explanation for the inhibition of malignant cell dissemination in vivo by nafazatrom.
Congenital erythropoietic porphyria affecting two brothers
Authors: None Herrera Saval, None Moruno Tirado
Journal: British Journal of Dermatology (1999)

We report two brothers, aged 5 and 2 years, with typical features of congenital erythropoietic porphyria. The elder did not receive medical attention until the age of 2 years, even though his urine had been red almost from birth, and despite severe scarring of the hands and face. The younger brother suffered haemolysis at birth. The uroporphyrinogen III cosynthase (URO IIIS) enzyme activity of red blood cells was 2% and 1.2% in the brothers, and genetic studies showed two different mutations of the URO IIIS gene, C73R and P248Q. The latter is a recently described mutation.
Immunization Studies With Mammary Tumor Virus&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jesse Charney, Dan H. Moore
Journal: JNCI Journal of the National Cancer Institute (1972)

A single intramuscular dose of purified, formalin-inactivated mammary tumor virus (MTV) completely protected C57BL (MTV-negative) mice subsequently challenged with live virus against MTV infection and mammary tumorigenesis. Similar immunization of Rill (MTV-positive) mice did not significantly reduce infection, but delayed tumor development by 1 month (50% tumor endpoint). The protective antigen appeared to be MTV specific. It was also shown that massive doses of infective MTV resulted in immunization rather than infection. The data support the hypothesis that MTV is specifically immunogenic. Adequate doses of live or inactivated virus act to stimulate antiviral immunity, whereas small inocula of a slowly replicating virus such as MTV are ineffective in this respect.
Maintaining vitamin D status in winter with ultraviolet B
Authors: L E Rhodes
Journal: British Journal of Dermatology (2012)

Journal Article Maintaining vitamin D status in winter with ultraviolet B Get access L.E. Rhodes L.E. Rhodes Photobiology Unit, Dermatology Centre, University of Manchester, Salford Royal NHS Foundation Hospital, Manchester M6 8HD, U.K. E‐mail: lesley.e.rhodes@manchester.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 2, 1 February 2012, Pages 238–239, https://doi.org/10.1111/j.1365-2133.2012.10801.x Published: 01 February 2012
Alteration of Cell-Surface Antigenicity of the Mouse Plasmacytoma. I. Immunologic Characterization of Surface Antigens Masked During Successive Transplantations2
Authors: Shinsuke Ohno, Shiyunnosuke Natsu-ume, Shunsuke Migita
Journal: JNCI Journal of the National Cancer Institute (1975)

Alterations of membrane antigenicity of IgA-synthesizing plasmacytoma cells (58-8) induced in a BALB/c mouse were investigated with rabbit antisera against 58-8 transplanted from 7-8 generations (anti-58-8) and mouse antisera against H-2d (anti-H-2d). The 58-8 cells transplanted (TP) for 8 generations (TP8), showed moderate susceptibilities to anti-58-8 [cytotoxicity index (CI) = 72%] and to anti-H-2d (Cl = 30-40%). At TP12, the susceptibility to anti-58-8 remained (tCl approximately 50%) but there was none to anti-H-2d (Cl = 0-10%). After TP13, 58-8 cells had detectable reactivity neither with anti-58-8 nor with anti-H-2d before proteolysis. However, antigenicity was demonstrated after treatment of cells with proteases: Anti-58-8 and anti-H-2d became cytotoxic to pronase-treated 58-8 (P-58-8) and these cytotoxic reactivities of antisera could be completely absorbed with P-58-8- but not with "intact" 58-8. Anti-H-2d absorbed with P-58-8 had no cytotoxicity to BALB/c spleen cells. Absorption of anti-H-2d with BALB/c spleen cells did not show any measurable cytotoxicity to P-58-8. Appearance of antigenicity after proteolysis was transient and reversible. When P-58-8 was incubated in vitro, susceptibilities to antisera were decreased. Actinomycin D and puromycin inhibited the loss of susceptibility; these metabolic inhibitors suppressed the "masking" of antigenic determinants with protein-like material(s). In early generations (TP8), 58-8 cells were susceptible to antiserum to bone marrow-derived lymphocytes (anti-B) and complement. The cells completely absorbed the cytotoxicity of anti-B against spleen cells. After additional transplantations (TP14, TP30), susceptibilities to anti-B were no longer detectable and no removal of the cytotoxicity was shown, though the cells were pretreated with pronase. Anti-B failed to kill MOPC-31C.