tbuckley/cabot-search huggingface dataset:
Low Prepregnancy Adiponectin Concentrations Are Associated With a Marked Increase in Risk for Development of Gestational Diabetes Mellitus
Authors: Monique M. Hedderson, Jeanne Darbinian, Peter J. Havel, Charles P. Quesenberry, Sneha Sridhar, Samantha Ehrlich, Assiamira Ferrara
Journal: Diabetes Care (2013)

To examine whether circulating total and high-molecular weight (HMW) adiponectin concentrations, measured before pregnancy, are associated with subsequent risk of gestational diabetes mellitus (GDM).This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up exam (1984-1996) with a serum sample obtained and who had a subsequent pregnancy (1984-2009). Eligible women were free of recognized diabetes. Case subjects were the 256 women who developed GDM. Two control subjects were selected for each case and matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies.Compared with the highest quartile of adiponectin, the risk of GDM increased with decreasing quartile (odds ratio [OR] 1.5 [95% CI 0.7-2.9], 3.7 [1.9-7.2], and 5.2 [2.6-10.1]; P(trend) <0.001) after adjustment for family history of diabetes, BMI, parity, race/ethnicity, cigarette smoking, and glucose and insulin concentrations. Similar estimates were observed for HMW (P(trend) <0.001). The combined effects of having total adiponectin levels below the median (<10.29 mg/mL) and being overweight or obese (BMI ≥25.0 kg/m(2)) were associated with a sevenfold increased risk of GDM compared with normal-weight women with adiponectin levels above the median (OR 6.7 [95% CI 3.6-12.5]).Prepregnancy low adiponectin concentrations, a marker of decreased insulin sensitivity and altered adipocyte endocrine function, is associated with reduced glucose tolerance during pregnancy and may identify women at high risk for GDM to target for early intervention.
Changes in the Mouse Estrus Cycle in Response to Brca1 Inactivation Suggest a Potential Link between Risk Factors for Familial and Sporadic Ovarian Cancer
Authors: Hao Hong, Hai-Yun Yen, Amy Brockmeyer, Ying Liu, Rajas Chodankar, Malcolm C. Pike, Frank Z. Stanczyk, Robert Maxson, Louis Dubeau
Journal: Cancer Research (2009)

Abstract Menstrual cycle activity is the most important risk factor for sporadic serous ovarian carcinoma, whereas a germ-line mutation in BRCA1 is the most important risk factor for the familial form. Given the rarity of BRCA1 mutations in sporadic ovarian cancers, we hypothesized that BRCA1 influences the menstrual cycle in a way that mimics the factors underlying sporadic ovarian cancer predisposition, making BRCA1 mutations redundant in such cancers. We compared the length of each phase of the estrus cycle (equivalent to the human menstrual cycle) and of circulating levels of estradiol in control mice and in mice carrying a Brca1 mutation in their ovarian granulosa cells, two thirds of which develop ovarian or uterine epithelial tumors. We also compared the length of the different phases of the cycle in mutants that subsequently developed tumors with those in mutants that remained tumor-free. Mutant mice as well as oophorectomized wild-type mice harboring mutant ovarian grafts showed a relative increase in the average length of the proestrus phase of the estrus cycle, which corresponds to the estrogen-dominated follicular phase of the human menstrual cycle. Total circulating levels of estradiol were also increased in mutant mice injected with pregnant mare serum gonadotropins. The relative increase in proestrus length was highest in mutant mice that subsequently developed reproductive epithelial tumors. We conclude that loss of a functional Brca1 increases murine ovarian epithelial tumor predisposition by increasing estrogen stimulation in the absence of progesterone, recapitulating conditions associated with sporadic ovarian cancer predisposition in humans. Cancer Res; 70(1); 221–8
Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits
Authors: C.H. Yang, A.M. Gonzalez-Angulo, J.M. Reuben, D.J. Booser, L. Pusztai, S. Krishnamurthy, D. Esseltine, J. Stec, K.R. Broglio, R. Islam, G.N. Hortobagyi, M. Cristofanilli
Journal: Annals of Oncology (2006)
Risk of tuberculosis following HIV seroconversion in high-income countries
Authors: Sara Lodi, Julia del Amo, Antonella d'Arminio Monforte, Sophie Abgrall, Caroline Sabin, Charles Morrison, Hansjakob Furrer, Roberto Muga, Kholoud Porter, Enrico Girardi
Journal: Thorax (2012)

Few data exist on tuberculosis (TB) incidence according to time from HIV seroconversion in high-income countries and whether rates following initiation of a combination of antiretroviral treatments (cARTs) differ from those soon after seroconversion.Data on individuals with well estimated dates of HIV seroconversion were used to analyse post-seroconversion TB rates, ending at the earliest of 1 January 1997, death or last clinic visit. TB rates were also estimated following cART initiation, ending at the earliest of death or last clinic visit. Poisson models were used to examine the effect of current and past level of immunosuppression on TB risk after cART initiation.Of 19 815 individuals at risk during 1982-1996, TB incidence increased from 5.89/1000 person-years (PY) (95% CI 3.77 to 8.76) in the first year after seroconversion to 10.56 (4.83 to 20.04, p=0.01) at 10 years. Among 11 178 TB-free individuals initiating cART, the TB rate in the first year after cART initiation was 4.23/1000 PY (3.07 to 5.71) and dropped thereafter, remaining constant from year 2 onwards averaging at 1.64/1000 PY (1.29 to 2.05). Current CD4 count was inversely associated with TB rates, while nadir CD4 count was not associated with TB rates after adjustment for current CD4 count, HIV-RNA at cART initiation.TB risk increases with duration of HIV infection in the absence of cART. Following cART initiation, TB incidence rates were lower than levels immediately following seroconversion. Implementation of current recommendations to prevent TB in early HIV infection could be beneficial.
Ali J. Marian
Authors: Ruth Williams
Journal: Circulation Research (2014)

New Leaders in Cardiovascular ScienceC ardiomyopathies-such as hypertrophic cardiomyopathy (ex- cess thickening of the heart muscle), dilated cardiomyopathy (thinning and weakening of the heart), and arrhythmogenic cardiomyopathy (replacement of heart muscle with fat cells and scar tissue)-are the leading cause of sudden cardiac death and can often be practically symptomless, until it is too late, or can manifest as arrhythmias or severe heart failure.Such cardiomyopathies are complex genetic diseases that can either be inherited or arise from de novo mutations, with many genes contributing to and modifying the condition.
Airborne particulate matter (PM10) decreases respiratory activity in mitochondria isolated from lung tissue
Authors: Norma Laura Delgado-Buenrostro, Verόnica Freyre-Fonseca, Claudia María García-Cuéllar, Yesennia Sánchez-Pérez, Yolanda I. Chirino
Journal: European Respiratory Journal (2011)

Airborne particulate matter (PM10) has potential adverse health effects in human, especially in lung tissue and those effects are related to an increase in several diseases and cancer. We have previously demonstrated that PM10 increases reactive oxygen species (ROS) formation, decrease in antioxidant enzymes activity and these effects are observed under sub-lethal conditions. In this regard, mitochondria are the main source of ROS but little is known about alterations induced in mitochondrial function after PM10 exposure. We hypothesized that if PM10 induces an increase in ROS generation, it could be possible to find alterations mitochondrial function. To test our hypothesis we exposed enriched mitochondria preparations from lung tissue of rat for 1 hour to the following PM10 concentrations: 1, 5, 10, 30 and 50 μg/mL. We measured the oxygen consumption after PM10 exposure using a Clark type electrode and also the activity of mitochondrial complexes. In addition, the mitochondrial membrane potential was determined by rhodamine 123 staining using confocal microscopy. Our results showed a decrease in the respiratory control index and ADP phosphorylation over 50%, a decrease in the activity of complex IV and an important decrease in mitochondrial membrane potential. In conclusion, PM10 induces a decrease in oxygen consumption, ADP phosphorylation and loss of mitochondrial membrane potential. These effects are related to the decrease in activity of complex IV. Our research will be guided to investigate if the mitochondrial alterations induced by PM10 exposure could be related to mitochondrial dysfunction and metabolic alterations found in cancer cells.
Female Lung Cancer
Authors: V L Ernster
Journal: Annual Review of Public Health (1996)

Female lung cancer death rates increased by more than 550 percent between 1950 and 1991. In 1986 lung cancer surpassed breast cancer to become the leading cause of cancer death in women in the United States. The lung cancer epidemic is primarily attributable to cigarette smoking, which is responsible for at least 80% of the disease in women. There are gender differences in the distribution of lung cancer by histologic type, even controlling for smoking, and some data suggest greater female than male susceptibility to lung cancer at a given level of smoking. Exposure to environmental tobacco smoke increases risk of lung cancer in nonsmoking women. Family history of lung cancer, personal history of lung disease (e.g. asthma, chronic bronchitis, pneumonia, or tuberculosis), and a history of radiotherapy also appear to be associated with increased risk. Data specific to women on the role of household radon exposures or of specific occupational or environmental exposures are relatively sparse and inconsistent. Finally, many studies have reported a decreased risk of lung cancer in individuals who consume high levels of fruits and vegetables; however, clinical trials fail to support a beneficial effect of beta-carotene supplementation. Since cigarette smoking accounts for the vast majority of lung cancer cases in women, efforts to prevent adolescent girls from starting to smoke and to encourage cessation among established smokers have the greatest potential for reducing the female lung cancer burden.
Regional differences in electrical and mechanical properties of myocytes from guinea-pig hearts with mild left ventricular hypertrophy
Authors: S Bryant
Journal: Cardiovascular Research (1997)

To investigate electrical and mechanical properties of single myocytes isolated from different regions of the left ventricle in control and hypertrophied hearts.Mild cardiac hypertrophy was induced in guinea-pigs by aortic constriction. Myocytes were isolated from basal sub-endocardial, basal mid-myocardial and apical sub-epicardial layers of the left ventricle. Action potentials were stimulated at 1 Hz. Membrane currents were measured using the switch-clamp technique. Cell shortening was measured using a photodiode array.In control hearts mean action potential duration (APD) was longer in sub-endocardial myocytes than in sub-epicardial myocytes. In hypertrophy APD was prolonged in sub-epicardial and mid-myocardial myocytes and unchanged in sub-endocardial myocytes (APD90 ms, control: sub-endocardial 273 +/- 12, mid-myocardial 254 +/- 14, sub-epicardial 229 +/- 9; hypertrophy: sub-endocardial 259 +/- 13, mid-myocardial 291 +/- 9, sub-epicardial 268 +/- 11, P < 0.005, ANOVA). There was no significant regional difference in APD in hypertrophied hearts. In control hearts L-type calcium current (ICa) was similar in all regions. In hypertrophy ICa was increased in sub-epicardial and mid-myocardial myocytes and reduced in sub-endocardial myocytes. Calcium-activated tail currents were not regionally different in control or hypertrophied hearts, but were increased in hypertrophy.Changes in electrical and mechanical properties associated with hypertrophy are not homogeneous throughout the left ventricle. The difference in APD between sub-endocardial and sub-epicardial myocytes seen in control hearts is lost in hypertrophy. These results may favour the propagation of re-entry arrhythmias in hypertrophied hearts.
Points: Subacute sclerosing panencephalitis
Authors: A O. Ogunmekan
Journal: BMJ (1980)

<h3>Background:</h3> Host- and pathogen-related factors associated with septic shock in pneumococcal pneumonia are not well defined. The aim of this study was to identify risk factors for septic shock and to ascertain patient outcomes. Serotypes, genotypes and antibiotic resistance of isolated strains were also analysed. <h3>Methods:</h3> Observational analysis of a prospective cohort of non-severely immunosuppressed hospitalised adults with pneumococcal pneumonia. Septic shock was defined as a systolic blood pressure of &lt;90 mm Hg and peripheral hypoperfusion with the need for vasopressors for &gt;4 h after fluid replacement. <h3>Results:</h3> 1041 patients with pneumococcal pneumonia diagnosed by Gram stain and culture of appropriate samples and/or urine antigen test were documented, of whom 114 (10.9%) had septic shock at admission. After adjustment, independent risk factors for shock were current tobacco smoking (OR, 2.11; 95% CI, 1.02 to 4.34; p = 0.044), chronic corticosteroid treatment (OR, 4.45; 95% CI, 1.75 to 11.32; p = 0.002) and serotype 3 (OR, 2.24; 95% CI, 1.12 to 4.475; p = 0.022). No significant differences were found in genotypes and rates of antibiotic resistance. Compared with the remaining patients, patients with septic shock required mechanical ventilation more frequently (37% vs 4%; p&lt;0.001) and had longer length of stay (11 vs 8 days; p&lt;0.001). The early (10% vs 1%; p&lt;0.001) and overall case fatality rates (25% vs 5%; p&lt;0.001) were higher in patients with shock. <h3>Conclusions:</h3> Septic shock is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Current tobacco smoking, chronic corticosteroid treatment and infection caused by serotype 3 are independent risk factors for this complication.
Smoking cessation with four nicotine replacement regimes in a lung clinic
Authors: P. Tønnesen, K.L. Mikkelsen
Journal: European Respiratory Journal (2000)

Smoking cessation is a key intervention for prevention of several lung diseases. The aim of the present study was to compare the effect of smoking cessation with nicotine replacement in a lung clinic in a low resource set-up suitable for implementation in other lung clinics. This was an open, randomized trial with 4 different nicotine replacement regimes combined with minimal behavioural support in daily routine. A total of 446 smokers (&gt;9 cigarettes x day(-1)) were allocated to a nurse-conducted smoking cessation programme with 4 treatment arms: a 5-mg nicotine patch ("placebo"), a 15-mg nicotine patch, nicotine inhaler, and a 15-mg nicotine patch plus nicotine inhaler. Recommended use of the nicotine products were 3 months with the possibility of continuing use up to 9 months on an individual basis. Individual follow-up studies were scheduled after 2 and 6 weeks, 3, 6, 9 and 12 months. The 12-month point prevalence was 6% (5-mg patch (placebo)), 16% (15-mg patch) (p&lt;0.05), 9% (inhaler) and 11% (15-mg patch plus inhaler), respectively. To conclude, the set-up investigated in this study which included minimal behavioural support with nicotine patches should be evaluated in other lung clinics, as it doubled success rate when compared to a placebo with a 1-yr point prevalence of 16% and also the resources used are limited.
Hematologic Disorders Associated With Primary Mediastinal Nonseminomatous Germ Cell Tumors
Authors: J. T. Hartmann, C. R. Nichols, J.-P. Droz, A. Horwich, A. Gerl, S. D. Fossa, J. Beyer, J. Pont, K. Fizazi, L. Einhorn, L. Kanz, C. Bokemeyer
Journal: JNCI Journal of the National Cancer Institute (2000)

BACKGROUND. The association between primary germ cell tumors of the mediastinum (the space between the lung pleura that contains the heart and other chest viscera) and hematologic malignancies has been described by retrospective analysis of patients treated at individual clinical centers. To better characterize the risk of hematologic disorders in patients with extragonadal germ cell tumors and to describe the clinical and biologic features of the disorders, we studied an unselected population in a large, international, multicenter database. METHODS. Six hundred thirty-five patients treated at 11 centers in the United States and Europe from 1975 through 1996 were evaluated retrospectively. RESULTS. A hematologic disorder was observed in 17 patients with germ cell tumors. All cases developed among the 287 patients with primary mediastinal nonseminomatous germ cell tumors, giving an incidence rate in this group of 2.0% (95% confidence interval [CI] = 1.1%-3.1%) per year over a median follow-up time of 3 years. The risk of developing hematologic disorders was statistically significantly increased in patients with primary mediastinal nonseminomatous germ cell tumors in comparison with the age-matched general population (standardized incidence ratio = 250; 95% CI = 140-405). The median time to onset of hematologic neoplasia was 6 months (range, 0-47 months), and the median survival after diagnosis of the hematologic disorder was 5 months (range, 0-16 months) (two-sided P<.0001, comparing survival from the time of diagnosis of the germ cell tumor of patients with and without hematologic disorders). CONCLUSION. In our study, approximately one in 17 patients with primary mediastinal nonseminomatous germ cell tumors was affected by a hematologic disorder, whereas no cases were seen among 334 patients with other extragonadal germ cell tumors. The hematologic disorder had a statistically significant impact on prognosis, with none of the 17 reported patients surviving for more than 2 years.
Minimally Invasive Epicardial Injections Using a Novel Semiautonomous Robotic Device
Authors: Takeyoshi Ota, Nicholas A. Patronik, David Schwartzman, Cameron N. Riviere, Marco A. Zenati
Journal: Circulation (2008)

We have developed a novel miniature robotic device (HeartLander) that can navigate on the surface of the beating heart through a subxiphoid approach. This study investigates the ability of HeartLander to perform in vivo semiautonomous epicardial injections on the beating heart.The inchworm-like locomotion of HeartLander is generated using vacuum pressure for prehension of the epicardium and drive wires for actuation. The control system enables semiautonomous target acquisition by combining the joystick input with real-time 3-dimensional localization of the robot provided by an electromagnetic tracking system. In 12 porcine preparations, the device was inserted into the intrapericardial space through a subxiphoid approach. Ventricular epicardial injections of dye were performed with a custom injection system through HeartLander's working channel. HeartLander successfully navigated to designated targets located around the circumference of the ventricles (mean path length=51+/-25 mm; mean speed=38+/-26 mm/min). Injections were successfully accomplished following the precise acquisition of target patterns on the left ventricle (mean injection depth=3.0+/-0.5 mm). Semiautonomous target acquisition was achieved within 1.0+/-0.9 mm relative to the reference frame of the tracking system. No fatal arrhythmia or bleeding was noted. There were no histological injuries to the heart due to the robot prehension, locomotion, or injection.In this proof-of-concept study, HeartLander demonstrated semiautonomous, precise, and safe target acquisition and epicardial injection on a beating porcine heart through a subxiphoid approach. This technique may facilitate minimally invasive cardiac cell transplantation or polymer therapy in patients with heart failure.
Distribution and turnover of Langerhans cells during delayed immune responses in human skin.
Authors: G Kaplan, A Nusrat, M D Witmer, I Nath, Z A Cohn
Journal: The Journal of Experimental Medicine (1987)

The changes in distribution and turnover of T6+ Langerhans cells (LC) in the skin during delayed immune responses to tuberculin, and in the lesions of tuberculoid leprosy and cutaneous Leishmaniasis were investigated. In each situation, there was a dermal accumulation of monocytes and T cells and epidermal thickening with keratinocyte Ia expression. In the tuberculin response a dramatic change in the distribution of LC was observed. By 41 h, T6+ LC were displaced to the upper zone of the thickening epidermis followed by an almost complete loss of LC from the epidermis by approximately 72 h. After 7 d, T6+ cells started to reappear in the epidermis, which regained almost normal numbers of T6+ LC by 14 d. After antigen administration and initiation of the delayed immune response, enhanced numbers of T6+ cells appeared in association with the mononuclear cell infiltrate of the upper dermal lesions. Their numbers peaked by 72 h, were reduced at 7 d, and again enhanced by 14 d, when the epidermis was being repopulated. Similar numbers of T6+ cells were found in the chronic lesions of tuberculoid leprosy and cutaneous Leishmaniasis but not lepromatous leprosy. The cells of the dermis were identified as typical LC by the presence of Birbeck granules and surface T6 antigen at the electron microscope level. These cells were closely associated with lymphocytes. We have quantified the number of LC, evaluated their directional flux into the epidermis and dermis, determined nearest neighbors, and made predictions as to their fate.
Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy
Authors: Yuki Ichimura, Takashi Matsushita, Yasuhito Hamaguchi, Kenzo Kaji, Minoru Hasegawa, Yoshinori Tanino, Yayoi Inokoshi, Kazuhiro Kawai, Takuro Kanekura, Maria Habuchi, Atsuyuki Igarashi, Ryosuke Sogame, Takashi Hashimoto, Tomohiro Koga, Ayako Nishino, Naoko Ishiguro, Naoki Sugimoto, Rui Aoki, Noriko Ando, Tetsuya Abe, Takashi Kanda, Masataka Kuwana, Kazuhiko Takehara, Manabu Fujimoto
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Methods Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Results Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb–IV). Conclusions While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.