tbuckley/cabot-search huggingface dataset:
Effect of acute and chronic beta-blockade on carbon dioxide sensitivity in normal man.
Authors: P F Hutchinson, R N Harrison
Journal: Thorax (1980)

The effect of beta-adrenoceptor antagonists on the respiratory response to carbon dioxide rebreathing was studied in eight normal subjects. Propranolol, atenolol, metoprolol, and placebo were given in random, double-blind fashion. Subjects were studied before each treatment period, after one dose, and after eight days of treatment with each drug. A rebreathing method was used to produce progressive hypercapnia and the respiratory response was assessed by measuring minute ventilation and maximum rate of change of inspiratory mouth pressure. Beta-blockade was assessed by the reduction in heart rate during steady state exercise on a cycle ergometer. There was no change in the respiratory response to carbon dioxide after a single dose or eight days treatment of any drug. All three active drugs produced a significant reduction in exercise heart rate. The forced expiratory volume in one second was not altered by any of the drugs.
IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation
Authors: Lue Dai, Kristy B. Lidie, Qian Chen, Joseph W. Adelsberger, Xin Zheng, DaWei Huang, Jun Yang, Richard A. Lempicki, Tauseef Rehman, Robin L. Dewar, Yanmei Wang, Ronald L. Hornung, Kelsey A. Canizales, Stephen J. Lockett, H. Clifford Lane, Tomozumi Imamichi
Journal: The Journal of Experimental Medicine (2013)

The susceptibility of macrophages to HIV-1 infection is modulated during monocyte differentiation. IL-27 is an anti-HIV cytokine that also modulates monocyte activation. In this study, we present new evidence that IL-27 promotes monocyte differentiation into macrophages that are nonpermissive for HIV-1 infection. Although IL-27 treatment does not affect expression of macrophage differentiation markers or macrophage biological functions, it confers HIV resistance by down-regulating spectrin β nonerythrocyte 1 (SPTBN1), a required host factor for HIV-1 infection. IL-27 down-regulates SPTBN1 through a TAK-1–mediated MAPK signaling pathway. Knockdown of SPTBN1 strongly inhibits HIV-1 infection of macrophages; conversely, overexpression of SPTBN1 markedly increases HIV susceptibility of IL-27–treated macrophages. Moreover, we demonstrate that SPTBN1 associates with HIV-1 gag proteins. Collectively, our results underscore the ability of IL-27 to protect macrophages from HIV-1 infection by down-regulating SPTBN1, thus indicating that SPTBN1 is an important host target to reduce HIV-1 replication in one major element of the viral reservoir.
Clonality of angioimmunoblastic lymphadenopathy and implications for its evolution to malignant lymphoma.
Authors: E H Lipford, H R Smith, S Pittaluga, E S Jaffe, A D Steinberg, J Cossman
Journal: Journal of Clinical Investigation (1987)

To investigate the relationship of the lymphoid hyperplasia of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) to supervening malignant lymphoma, we subjected DNA from lymph nodes and peripheral blood mononuclear cells from five AILD patients to Southern blot analysis to detect clonal rearrangements of immunoglobulin and T-cell receptor genes. Lymph nodes and peripheral blood from AILD patients were found to contain clones of lymphoid cells harboring either immunoglobulin or T-cell receptor gene rearrangements that, in some instances, regressed during the course of disease. A lymph node from one patient was involved by immunoblastic lymphoma and manifested an additional gene rearrangement pattern not seen in premalignant specimens from that patient. In contrast, DNA obtained from normal peripheral blood mononuclear cells and 11 examples of other forms of lymphoid hyperplasia showed no gene rearrangements. As a disorder of cellular immunoregulation in which lymphoid cells may escape normal growth controls, AILD provides a natural model to dissect stages of lymphomagenesis in man.
Reduction of Stroke Incidence After Myocardial Infarction With Pravastatin
Authors: Jonathan F. Plehn, Barry R. Davis, Frank M. Sacks, Jean L. Rouleau, Marc A. Pfeffer, Victoria Bernstein, T. Edward Cuddy, Lemuel A. Moyé, Linda B. Piller, John Rutherford, Lara M. Simpson, Eugene Braunwald
Journal: Circulation (1999)

Background —The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease. Methods and Results —To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, pravastatin lowered total serum cholesterol by 20%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P =0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P =0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 versus 6, respectively). Conclusions —Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infarction in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy.
Short ragweed pollen triggers allergic inflammation through Toll-like receptor 4–dependent thymic stromal lymphopoietin/OX40 ligand/OX40 signaling pathways
Authors: De-Quan Li, Lili Zhang, Stephen C. Pflugfelder, Cintia S. De Paiva, Xiaobo Zhang, Guiqiu Zhao, Xiaofen Zheng, Zhitao Su, Yangluowa Qu
Journal: Journal of Allergy and Clinical Immunology (2011)
Breast cancer in young women and its impact on reproductive function
Authors: M. Hickey, M. Peate, C.M. Saunders, M. Friedlander
Journal: Human Reproduction Update (2009)

BACKGROUNDBreast cancer is the most common cancer in women in developed countries, and 12% of breast cancer occurs in women 20–34 years. Survival from breast cancer has significantly improved, and the potential late effects of treatment and the impact on quality of life have become increasingly important. Young women constitute a minority of breast cancer patients, but commonly have distinct concerns and issues compared with older women, including queries regarding fertility, contraception and pregnancy. Further, they are more likely than older women to have questions regarding potential side effects of therapy and risk of relapse or a new primary. In addition, many will have symptoms associated with treatment and they present a management challenge. Reproductive medicine specialists and gynaecologists commonly see these women either shortly after initial diagnosis or following adjuvant therapy and should be aware of current management of breast cancer, the options for women at increased genetic risk, the prognosis of patients with early stage breast cancer and how adjuvant systemic treatments may impact reproductive function.
Acute viral infection results in a PD-1-dependent loss of anti-tumor CD8+ T cell responses: implications for tumor immunotherapy
Authors: Frederick Kohlhapp, Erica Huelsmann, Joseph Broucek, Jason Schenkel, Howard Kaufman, Andrew Zloza
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Oncolytic viruses are gaining acceptance as a method of tumor immunotherapy, and some studies have reported improved anti-tumor T cell responses after acute pyretic non-oncolytic infections. Therefore, we hypothesized that viral infections may aid in the immunotherapy of cancer.
Proteasome-Mediated Degradation and Functions of Hematopoietic Progenitor Kinase 1 in Pancreatic Cancer
Authors: Hua Wang, Xianzhou Song, Craig Logsdon, Guisheng Zhou, Douglas B. Evans, James L. Abbruzzese, Stanley R. Hamilton, Tse-Hua Tan, Huamin Wang
Journal: Cancer Research (2009)

Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. In this study, we examined the expression, regulation, and functions of HPK1 in pancreatic ductal adenocarcinomas (PDA). We found that loss of HPK1 protein expression correlated significantly with the progression of pancreatic intraepithelial neoplasias (P = 0.001) and development of invasive PDA. Similarly, HPK1 protein was not expressed in any of eight PDA cell lines examined but was expressed in immortalized human pancreatic duct epithelial (HPDE) cells. There was no difference in HPK1 mRNA levels in PDA cell lines or primary PDA compared with those in HPDE cells or ductal epithelium in chronic pancreatitis and normal pancreas, respectively. Treatment of Panc-1 cells with a proteasome inhibitor, MG132, increased the HPK1 protein levels in a dose-dependent manner, suggesting that alteration in proteasome activity contributes to the loss of HPK1 protein expression in pancreatic cancer. Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. After MG132 withdrawal, wild-type HPK1 protein expression was markedly decreased within 24 hours, but kinase-dead HPK1 mutant protein expression was sustained for up to 96 hours. Therefore, HPK1 kinase activities were required for the loss of HPK1 protein in PDAs. Furthermore, restoring wild-type HPK1 protein in PDA cells led to the increase in p21 and p27 protein expression and cell cycle arrest. Thus, HPK1 may function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer.
Release of prostaglandin E2 and leukotriene B4 by alveolar macrophages from patients with sarcoidosis
Authors: V. De Rose, L. Trentin, M. T. Crivellari, A. Cipriani, G. Gialdroni Grassi, E. Pozzi, G. Folco, G. Semenzato
Journal: Thorax (1997)

BACKGROUND: Mediators released by alveolar macrophages, as well as by T cells, play an important part in modulating local immune processes in sarcoidosis. Among alveolar macrophage secretory products, arachidonic acid metabolites are known to regulate inflammatory and immune reactions. It has been suggested that cyclo-oxygenase and lipoxygenase pathway metabolites of arachidonic acid modulate the evolution of the granulomatous inflammatory response in the lung differently. METHODS: Alveolar macrophages recovered from the bronchoalveolar lavage (BAL) fluid of 32 patients with sarcoidosis in different states of disease activity and 10 normal subjects were evaluated for their ability to release prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Alveolar macrophages were cultured in the presence or absence of opsonised zymosan (500 micrograms/ml), and PGE2 and LTB4 levels in the culture supernatants were determined by enzyme immunoassay (EIA). RESULTS: Stimulated alveolar macrophages from patients with active sarcoidosis released higher LTB4 levels than those from normal subjects, but no differences in PGE2 release were observed between the two groups. The time course of LTB4 release by activated alveolar macrophages showed that normal cells produced similar levels of the hydroxyacid during the early and late times of culture while LTB4 release by activated cells from patients with sarcoidosis increased markedly after 60 minutes of culture, remaining elevated until 24 hours. Indomethacin (3 x 10(6) M) caused the expected inhibition of PGE2 formation without affecting LTB4 release. CONCLUSIONS: These results suggest that alveolar macrophages from the BAL fluid of patients with active sarcoidosis are primed to release LTB4, which may contribute to the locally heightened immune response.
MITOCHONDRIAL M2 AUTOANTIGENS AND PRIMARY BILIARY CIRRHOSIS
Authors: S Marzuki, L.H Moehario, R.J Devenish, I.R Mackay, P.M Smooker, PeterA Berg, Reinhild Klein, A.K Burroughs, P Butler, W Brumfitt, H Baum
Journal: The Lancet (1989)
Bronchoalveolar lavage cell counts as a predictor of short term outcome in pulmonary sarcoidosis.
Authors: N M Foley, A P Coral, K Tung, B N Hudspith, D G James, N M Johnson
Journal: Thorax (1989)

Sixty seven patients with biopsy proven pulmonary sarcoidosis were prospectively studied to determine whether single point bronchoalveolar lavage cell counts were a useful indicator of functional outcome and whether repeated lavage helped in management. The mean follow up period was 25 (range 13-37) months. No patient was having corticosteroid treatment at the time of initial bronchoalveolar lavage. "High intensity alveolitis" (lymphocyte count greater than or equal to 28%) was present at the initial lavage in 42 patients. These patients showed a significant improvement in their pulmonary function and chest radiographs over the follow up period whereas patients with "low intensity alveolitis" did not. Of the 42 patients with high intensity alveolitis, 31 had chronic sarcoidosis (duration over two years, mean 80 months). These patients showed a significant improvement in FVC but not in TLCO. Corticosteroids resulted in greater functional and radiological improvement in the patients with high intensity alveolitis than in those with low intensity alveolitis. Repeat bronchoalveolar lavage in 34 patients, mean 8.4 months after the original lavage, showed a weak inverse relation between a reduced lymphocyte count and change in forced vital capacity and isotope uptake on a gallium scan. These correlations were too weak to make repeated cell counts useful in management. Our results suggest that high intensity alveolitis may be a favourable prognostic factor for lung function in pulmonary sarcoidosis, even in patients with chronic disease, but that repeat lavage adds little to the management of the individual patient.
Bedaquiline in MDR/XDR-TB cases: first experience on compassionate use
Authors: Simon Tiberi, Saverio De Lorenzo, Rosella Centis, Pietro Viggiani, Lia D’Ambrosio, Giovanni Battista Migliori
Journal: European Respiratory Journal (2013)

To the Editor: 

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are recognised as global emerging public health priorities [1, 2], with 310 000 MDR-TB cases notified to the World Health Organization (WHO) in 2011, 9% of them being XDR. MDR/XDR-TB testify to the failure of National TB Programmes to use available first- and second-line drugs correctly [3], and generate clinical dilemmas for clinicians managing these difficult-to-treat cases.

The chances of achieving treatment success, or even sputum smear and culture conversion, are largely suboptimal in these cases [1, 2]. In the largest MDR-TB cohort ever analysed [1, 2], the proportion of cases treated successfully was 54%, with 8% failing or relapsing, 15% dying and 23% defaulting. In the XDR-TB subgroup, 40% achieved treatment success, 22% failed treatment or relapsed, 15% died, and 16% defaulted.

The reason for this is simple: treatment of MDR/XDR-TB is expensive [4], more toxic [5, 6], and, as of today, takes up to 2 years of therapy according to current WHO guidelines [3]. The therapeutic armamentarium is limited in XDR-TB cases, where, by definition, the strains of Mycobacterium tuberculosis are resistant to the two most powerful anti-TB drugs (rifampicin and isoniazid, defining MDR-TB) plus any fluoroquinolones and to at least one second-line injectable (amikacin, capreomycin and kanamycin). The remaining treatment options available are the “old” bacteriostatic drugs and the not well-known WHO group 5 drugs [3, 5–7].

The real …
Gestational Diabetes Mellitus: Clinical Predictors and Long-Term Risk of Developing Type 2 Diabetes
Authors: Anna J. Lee, Richard J. Hiscock, Peter Wein, Susan P. Walker, Michael Permezel
Journal: Diabetes Care (2007)

OBJECTIVE—We sought to determine the long-term risk of type 2 diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM) and assess what maternal antepartum, postpartum, and neonatal factors are predictive of later development of type 2 diabetes. RESEARCH DESIGN AND METHODS—This was a retrospective cohort study using survival analysis on 5,470 GDM patients and 783 control subjects who presented for postnatal follow-up at the Mercy Hospital for Women between 1971 and 2003. RESULTS—Risk of developing diabetes increased with time of follow-up for both groups and was 9.6 times greater for patients with GDM. The cumulative risk of developing type 2 diabetes for the GDM patients was 25.8% at 15 years postdiagnosis. Predictive factors for the development of type 2 diabetes were use of insulin (hazard ratio 3.5), Asian origin compared with Caucasian (2.1), and 1-h blood glucose (1.3 for every 1 mmol increase above 10.1 mmol). BMI was associated with an increased risk of developing type 2 diabetes but did not meet the assumption of proportional hazards required for valid inference when using Cox proportional hazards. CONCLUSIONS—While specific predictive factors for the later development of type 2 diabetes can be identified in the index pregnancy, women with a history of GDM, as a group, are worthy of long-term follow-up to ameliorate their excess cardiovascular risk.
Diabetes in Nonveterans, Veterans, and Veterans Receiving Department of Veterans Affairs Health Care
Authors: Gayle E. Reiber, Thomas D. Koepsell, Charles Maynard, Linda B. Haas, Edward J. Boyko
Journal: Diabetes Care (2004)

To compare behavioral risk factors and health and disease characteristics among three groups of adults with diabetes: nonveterans, veterans not receiving Department of Veterans Affairs (VA) health care, and veterans using VA services.Two data sources were used to describe the veteran population. First, the 2000 Behavioral Risk Factor Surveillance System (BRFSS) characterized the U.S. adult population by preventive health practices and risk behaviors linked to chronic and preventable diseases. New to the 2000 survey were questions on veteran status, which were administered in all states. Second, VA administrative and veterans benefits data were analyzed to describe comorbidity, education services, and veterans benefits.The estimated prevalence of diabetes in male veterans receiving VA care was 16%. Male veterans with diabetes using VA care were more likely to be nonwhite, not employed, have lower income, lower health status, and more activity limitations than male veterans not using these services. Computerized records indicate VA users with diabetes also had high concurrent comorbidity. Frequency of VA diabetes and preventive care services, as measured by selected quality indicators, was equivalent to or higher than the levels reported by veterans not receiving VA care and nonveterans. In addition to health care, nearly one-fourth of veterans with diabetes also received monthly awards for compensation and pension.Males receiving VA care with self-reported diabetes indicated receiving preventive care services at equivalent or higher levels than their counterparts receiving care outside the VA and nonveterans.
Haplotype Structure and Evidence for Positive Selection at the Human IL13 Locus
Authors: Gangqiao Zhou, Yun Zhai, Xiaojia Dong, Xiumei Zhang, Fengying He, Kaixin Zhou, Yunping Zhu, Handong Wei, Zhijian Yao, Shaofei Zhong, Yan Shen, Boqing Qiang, Fuchu He
Journal: Molecular Biology and Evolution (2003)

Interleukin-13 (IL13) is believed to play an important role in the pathogenesis of atopy and allergic asthma. To better understand genetic variation at the IL13 locus, we resequenced a 5.1-kb genomic region spanning the entire locus and identified 26 single-nucleotide polymorphisms (SNPs) in 74 individuals from three major populations—Chinese, Caucasian, and African. Our survey suggests exceptionally high and significant geographic structure at the IL13 locus between African and outside Africa populations. This unusual pattern suggests that positive selection that acts in some local populations may have played a role on the IL13 locus. In support of this suggestion, we found a significant excess of high frequency–derived SNPs in the Chinese population and Caucasian population, respectively, as expected after a recent episode of positive selection. Further, the unusual haplotype structure indicates that different scenarios of the action of positive selection on the IL13 locus in different populations may exist. In the Caucasian population, the skewed haplotype distribution dominated by one common haplotype supports the hypothesis of simple directional selection. Whereas, in the Chinese population, the two-round hitchhiking hypothesis may explain the skewed haplotype structure with three dominant ones. These findings may provide insight into the likely relative roles of selection and population history in establishing present-day variation at the IL13 locus, and, motivate further studies of this locus as an important candidate in common diseases association studies.
Mastocytosis and atopy: a study of 33 patients with urticaria pigmentosa
Authors: U. Müller, A. Helbling, T. Hunziker, B. Wüthrich, A. Pécoud, S. Gilardi, E. Beretta, J. Fasel, W. Messerli, P. Maurer
Journal: Allergy (1990)

Thirty-three patients with histologically verified urticaria pigmentosa were studied for coexisting atopic disease by means of history, skin prick testing with five common inhalants and serological investigation for total IgE and specific IgE antibodies to five common inhalants. The prevalence of atopy in urticaria pigmentosa was similar to that observed in the normal Swiss population, both on the basis of history (7/33 = 21%) and of positive skin prick tests to common inhalants (12/33 = 36%). However, total serum IgE levels were significantly lower (geometric mean value 16.8 kU/l) than in a control group of 52 Swiss blood donors of comparable age and sex distribution (geometric mean value 43.0 kU/l, t = 2.93, P less than 0.005). Specific IgE antibodies to common inhalants were also observed less frequently in urticaria pigmentosa patients than in controls, although this difference was not statistically significant. Low total and specific IgE values in patients with urticaria pigmentosa may be explained by increased absorption of circulating IgE to abundant tissue mast cells.