tbuckley/cabot-search huggingface dataset:
Macroalbuminuria Is a Better Risk Marker than Low Estimated GFR to Identify Individuals at Risk for Accelerated GFR Loss in Population Screening
Authors: Nynke Halbesma, Dirk-Sjoerd Kuiken, Auke H. Brantsma, Stephan J.L. Bakker, Jack F.M. Wetzels, Dick De Zeeuw, Paul E. De Jong, Ronald T. Gansevoort
Journal: Journal of the American Society of Nephrology (2006)

Macroalbuminuria, erythrocyturia, and impaired renal function are strong predictors of poor renal outcome in patients with known renal disease. However, the yield of mass screening for these variables to identify individuals who are at risk for GFR loss is yet unknown in a Western population. With the use of data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study, a prospective, population-based cohort study, the cardiovascular and renal prognosis was investigated in patients with classical renal risk markers: Macroalbuminuria (≥300 mg albumin/24 h urine), erythrocyturia (≥250 erythrocytes/L, without leukocyturia), and impaired renal function (both 24-h creatinine clearance and Modification of Diet in Renal Disease clearance below the fifth percentile of age- and gender-matched control subjects). The 8592 patients who were included in this study were followed for a 4-yr period. We identified 134 patients with macroalbuminuria, 128 with erythrocyturia, and 103 with impaired renal function. There was only a little overlap among the three groups. The prevalence of macroalbuminuria, erythrocyturia, and impaired renal function was calculated to be in the general population 0.6, 1.3, and 0.9%, respectively. In all three groups, fewer than 30% of patients were known to have this laboratory abnormality before screening. The incidence of cardiovascular disease was high in the macroalbuminuria group (<i>e.g.</i>, the age- and gender-adjusted hazard ratio for mortality as a result of cardiovascular disease is 2.6 [1.1 to 6.0]) and for the impaired renal function group (3.4 [1.5 to 8.0]). After a mean follow-up of 4.2 yr, the macroalbuminuria group showed a −7.2 ml/min per 1.73 m<sup>2</sup> estimated GFR (eGFR) loss, compared with −2.3 ml/min per 1.73 m<sup>2</sup> in the control group (difference <i>P</i> &lt; 0.001), whereas the rate of eGFR loss in the impaired renal function group (−0.2 ml/min per 1.73 m<sup>2</sup>; <i>P</i> = 0.18) and the erythrocyturia group (−2.6 ml/min per 1.73 m<sup>2</sup>) was not different from the control group. Macroalbuminuria and impaired renal function both predict a worse prognosis with respect to cardiovascular morbidity and mortality. However, macroalbuminuria is a better risk marker than low eGFR or erythrocyturia to identify in population screening of individuals who are at risk for accelerated GFR loss.
Lifetime Socioeconomic Position and Twins' Health: An Analysis of 308 Pairs of United States Women Twins
Authors: Nancy Krieger, Jarvis T Chen, Brent A Coull, Joe V Selby
Journal: PLoS Medicine (2005)

Background Important controversies exist about the extent to which people's health status as adults is shaped by their living conditions in early life compared to adulthood. These debates have important policy implications, and one obstacle to resolving them is the relative lack of sufficient high-quality data on childhood and adult socioeconomic position and adult health status. We accordingly compared the health status among monozygotic and dizygotic women twin pairs who lived together through childhood (until at least age 14) and subsequently were discordant or concordant on adult socioeconomic position. This comparison permitted us to ascertain the additional impact of adult experiences on adult health in a population matched on early life experiences. Methods and Findings Our study employed data from a cross-sectional survey and physical examinations of twins in a population-based twin registry, the Kaiser Permanente Women Twins Study Examination II, conducted in 1989 to 1990 in Oakland, California, United States. The study population was composed of 308 women twin pairs (58% monozygotic, 42% dizygotic); data were obtained on childhood and adult socioeconomic position and on blood pressure, cholesterol, post-load glucose, body mass index, waist-to-hip ratio, physical activity, and self-rated health. Health outcomes among adult women twin pairs who lived together through childhood varied by their subsequent adult occupational class. Cardiovascular factors overall differed more among monozygotic twin pairs that were discordant compared to concordant on occupational class. Moreover, among the monozygotic twins discordant on adult occupational class, the working class twin fared worse and, compared to her professional twin, on average had significantly higher systolic blood pressure (mean matched difference = 4.54 mm Hg; 95% confidence interval [CI], 0.10–8.97), diastolic blood pressure (mean matched difference = 3.80 mm Hg; 95% CI, 0.44–7.17), and low-density lipoprotein cholesterol (mean matched difference = 7.82 mg/dl; 95% CI, 1.07–14.57). By contrast, no such differences were evident for analyses based on educational attainment, which does not capture post-education socioeconomic position. Conclusion These results provide novel evidence that lifetime socioeconomic position influences adult health and highlight the utility of studying social plus biological aspects of twinship.
Immunity Induced Against the Brown-Pearce Carcinoma
Authors: F. S. Cheever, C. A. Janeway
Journal: Cancer Research (1941)

SUMMARY ~. In confirmation of Besredka's reports, it was observed that over 9 ~ per cent of intradermal Brown- Pearce carcinomas regressed spontaneously, and that rabbits with intracutaneous tumors, or in which these tunmrs had regressed, were refractory to subsequent implantations of the tumor. 2. Pathological and immunological studies shed no light on the fundamental nature of this immunity. The possibility of its being a nonspecific tissue reaction is discussed. REFERENCES i. B~-SREDKA, A., and L. GRoss. L'~pith61ioma intracutan~ du lapin et son pouvoir immunisant. Ann. Inst. Pasteur 57:343-356- I936. 2. BESREDKA, A., and L. GROSS. De la nature de l'immunit6 acquise vis-a-vis de l'~pith~lioma chez le lapin. Ann. Inst. Pasteur 6o:5-12. 1938. 3. BESREDKA, A., I. MAC, AT, P. LAVAL, and P. BESNARD. L'6pith61ioma intracutan6 du lapin et son pouvoir im- munisant. Ann. Inst. Pasteur 56:I25-I36. I936. 4. BROW~, W. H., and L. PEARCE. Studies Based on a Malig- nant Tumor of the Rabbit. I. The Spontaneous Tumor and Associated Abnormalities. J. Exper. Med. 37:6oI- 629. 1923. 5- BRow~, W. H., and L. PEARCE. Studies Based on a Malig- nant Tumor of the Rabbit. III. Intratesticular Trans- plantation and Clinical Course of the Disease. J. Exper. Med. 37:799-8IO. 1923. 6. Brown, W. H., L. PEARCE, and C. M. VA~ ALLEN. Studies based on a Malignant Tumor of the Rabbit. VI. Varia- tions in Growth and Malignancy of Transplanted Tumors. Part I. Results of Transplantation for the First Twenty Generations. J. Exper. Med. 4o:583-602. I9a4. 7- BROWN, W. H., L. PEARCE, and C. M. VAN ALLEN. Studies Based on a Malignant Tumor of the Rabbit. VI. Varia- tions in Growth and Malignancy of Transplanted Tumors. Part 2. Factors Influencing Results of Serial Transplanta- tion. J. Exper. Med. 4o:6o3-6i 7. I924. 8. CASEY, A. E. The Reaction of Standard Breeds os Rabbits to the Brown-Pearce Tumor. Am. J. Cancer ,31:446- 456. 1937- 9. EISE~, M. J., and A. LANCER. Osservazioni sul tumore di Brown-Pearce del coniglio. Tumori 12:55-62. 1938. I o. FLAKS, J., and B. GRY,XKRAt3X. La greffe intracutan6e immunise-t-elle l'organisme contre les nc~oplasmes? Compt. rend. Soc. de biol. I22:835-838. I936. 1I. KIDD, J. G. A Distinctive Substance Associated with the Brown-Pearce Rabbit Carcinoma. I. Presence and Spe- cificity of the Substance as Determined by Serum Reac- tions. J. Exper. Med. 7I:335-35o. 194 o.
PD-1 Co-inhibitory and OX40 Co-stimulatory Crosstalk Regulates Helper T Cell Differentiation and Anti-Plasmodium Humoral Immunity
Authors: Ryan A. Zander, Nyamekye Obeng-Adjei, Jenna J. Guthmiller, Divine I. Kulu, Jun Li, Aissata Ongoiba, Boubacar Traore, Peter D. Crompton, Noah S. Butler
Journal: Cell Host & Microbe (2015)
Etoposide and Cisplatin Chemotherapy for Metastatic Good-Risk Germ Cell Tumors
Authors: G. Varuni Kondagunta, Jennifer Bacik, Dean Bajorin, Deborah Dobrzynski, Joel Sheinfeld, Robert J. Motzer, George J. Bosl
Journal: Journal of Clinical Oncology (2005)

To assess response, overall survival, and relapse-free survival of patients with good-risk metastatic germ cell tumor (GCT) by International Germ Cell Consensus Classification Group (IGCCCG) criteria treated with four cycles of etoposide and cisplatin (EP).Two hundred eighty-nine patients with IGCCCG good-risk GCT were treated with four cycles of EP. EP consisted of four cycles of etoposide 100 mg/m2 and cisplatin 20 mg/m2 on days 1 to 5 every 21 days.Two hundred eighty-two of 289 patients (98%) achieved a complete response; 269 (93%) responded to chemotherapy alone and 13 (5%) responded to chemotherapy plus surgical resection of viable disease (GCT other than mature teratoma). Seventeen (6%) experienced relapse, and nine (3%) died as a result of disease at a median follow-up of 7.7 years (range, 0.4 to 21.1 years). Sixty-two of 204 patients (30%) with nonseminoma had findings of teratoma or viable GCT at postchemotherapy surgery.Four cycles of EP is a highly effective therapy for patients with good-risk GCT, with a high cure rate, low relapse rate, and little evidence of late relapse. Postchemotherapy surgery resection of residual disease remains an important aspect of treatment for these patients. Four cycles of EP is acceptable as a standard regimen for the treatment of good-risk metastatic GCT, and serves as an alternative to three cycles of bleomycin and etoposide before cisplatin.
IMMUNOLOGY OF MULTIPLE SCLEROSIS
Authors: Mireia Sospedra, Roland Martin
Journal: Annual Review of Immunology (2005)

▪ Abstract Multiple sclerosis (MS) develops in young adults with a complex predisposing genetic trait and probably requires an inciting environmental insult such as a viral infection to trigger the disease. The activation of CD4 + autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease. Damage of the target tissue, the central nervous system, is, however, most likely mediated by other components of the immune system, such as antibodies, complement, CD8 + T cells, and factors produced by innate immune cells. Perturbations in immunomodulatory networks that include Th2 cells, regulatory CD4 + T cells, NK cells, and others may in part be responsible for the relapsing-remitting or chronic progressive nature of the disease. However, an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.
Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children's Oncology Group trial A9961
Authors: Roger J. Packer, Tianni Zhou, Emi Holmes, Gilbert Vezina, Amar Gajjar
Journal: Neuro-Oncology (2012)

The purpose of the trial was to determine the survival and incidence of secondary tumors in children with medulloblastoma receiving radiotherapy plus chemotherapy. Three hundred seventy-nine eligible patients with nondisseminated medulloblastoma between the ages of 3 and 21 years were treated with 2340 cGy of craniospinal and 5580 cGy of posterior fossa irradiation. Patients were randomized between postradiation cisplatin and vincristine plus either CCNU or cyclophosphamide. Survival, pattern of relapse, and occurrence of secondary tumors were assessed. Five- and 10-year event-free survivals were 81 ± 2% and 75.8 ± 2.3%; overall survivals were 87 ± 1.8% and 81.3 ± 2.1%. Event-free survival was not impacted by chemotherapeutic regimen, sex, race, age at diagnosis, or gender. Seven patients had disease relapse beyond 5 years after diagnosis; relapse was local in 4 patients, local plus supratentorial in 2, and supratentorial alone in 1. Fifteen patients experienced secondary tumors as a first event at a median time of 5.8 years after diagnosis (11 >5 y postdiagnosis). All non-CNS solid secondary tumors (4) occurred in regions that had received radiation. Of the 6 high-grade gliomas, 5 occurred >5 years postdiagnosis. The estimated cumulative 10-year incidence rate of secondary malignancies was 4.2% (1.9%–6.5%). Few patients with medulloblastoma will relapse ≥5 years postdiagnosis; relapse will occur predominantly at the primary tumor site. Patients are at risk for development of secondary tumors, many of which are malignant gliomas. This may become an increasing issue as more children survive.
Tuberculosis transmission between foreign- and native-born populations in the EU/EEA: a systematic review
Authors: Andreas Sandgren, Monica Sañé Schepisi, Giovanni Sotgiu, Emma Huitric, Giovanni Battista Migliori, Davide Manissero, Marieke J. van der Werf, Enrico Girardi
Journal: European Respiratory Journal (2013)

Tuberculosis (TB) control programmes of many low TB incidence countries of the European Union/European Economic Area (EU/EEA) perceive challenges in controlling TB due to high numbers of TB in migrants from high-incidence countries. To assess the extent of TB transmission from the foreign-born to the native-born population, we quantitatively investigated the dynamics of TB transmission between these populations in the EU/EEA, using published molecular epidemiological studies. We searched PubMed and EMBASE databases from 1990 to August 2012. We identified 15 studies performed during 1992–2007 covering 12,366 cases, of which median (range) 49.2% (17.7%–86.4%) were foreign-born. The proportion of clustered isolates ranged between 8.5% and 49.1% of the total number of TB cases genotyped and among these, foreign-born cases were equally or more likely to have unique isolates compared to native-born cases. One third of the clusters were “mixed”, i.e. composed of foreign- and native-born cases, involving 0–34.2% of all genotyped cases. Cross-transmission among foreign and native populations was bidirectional, with wide differences across studies. This systematic review provides evidence that TB in a foreign-born population does not have a significant influence on TB in the native population in EU/EEA.
Zoledronic Acid Inhibits Visceral Metastases in the 4T1/luc Mouse Breast Cancer Model
Authors: Toru Hiraga, Paul J. Williams, Akimi Ueda, Daisuke Tamura, Toshiyuki Yoneda
Journal: Clinical Cancer Research (2004)

Abstract Purpose: It is established that bisphosphonates (BPs), specific inhibitors of osteoclasts, have beneficial effects on bone metastases of breast cancer. In addition, recent studies have reported that BPs have anticancer effects and suppress visceral metastases, too. However, the results of clinical studies are still conflicting. In the present study, we examined the effects of the BP zoledronic acid (ZOL), one of the most potent BPs currently available, on visceral metastases of breast cancer using an animal model in which mouse breast cancer cells 4T1/luc implanted at the orthotopic mammary fat pad spontaneously metastasize to multiple organs including bone, lung, and liver in female BALB/c mice. Experimental Design and Results: The 4T1/luc-bearing mice received single or four i.v. injections of ZOL (0.5 or 5 μg/mouse) during the whole experimental period. Bone metastases were reduced by the ZOL treatment. More importantly, ZOL significantly suppressed lung and liver metastases. Furthermore, ZOL prolonged overall survival of the tumor-bearing mice. Of interest, apoptosis in 4T1/luc cells colonized in bone was increased by ZOL; however, those in lung were not changed. In vitro studies demonstrated that ZOL inhibited cell migration and invasion and promoted apoptosis of 4T1/luc cells. Conclusions: These results are consistent with the notion that ZOL affects breast cancer metastasis to visceral organs as well as bone. These effects of ZOL may be attributable to inhibition of migration and invasion of breast cancer cells. Clinical relevance of our experimental results needs to be determined in breast cancer patients with visceral metastases.
Swine aortic smooth muscle in tissue culture. Some effects of purified swine lipoproteins on cell growth and morphology.
Authors: B G Brown, R Mahley, G Assmann
Journal: Circulation Research (1976)

Smooth muscle cells (SMC) were grown from inner media explants of swine aorta and used as a model for studying the role of lipoproteins in atherogenesis. These cultured cells retain the characteristics of SMC through multiple passages. Cell growth curves, in time, were obtained by using standard counting techniques, SMC grew slowly (0.019 cycle/day) in modified Dulbecco-Vogt medium supplemented with 1.5% swine serum. Purified lipoproteins were prepared from three normolipidemic and two hyperlipidemic (cholesterol-fed) swine. When the medium of 84 growth experiments was supplemented with these lipoproteins, SMC growth rate increased linearly with lipoprotein cholesterol concentration up to 10 mg/dl. At 10 mg/dl of lipoprotein cholesterol, very low density lipoproteins (VLDL) increased growth rate 7.2-fold (P less than 0.01); low density lipoproteins (LDL) 5.7-fold (P less than 0.01); high density lipoproteins (HDL2) 3,4-fold (P less than 0.02); and HDLc, and lipoprotein appearing in the hyperlipidemic swine, 3.0-fold (P less than 0.01). Addition of 10% lipoprotein-free serum stimulated growth rate 6.0-fold (P less than 0.01). There was no difference between normo- and hyperlipidemic lipoproteins with respect to cell growth rate. Factors present in the ultracentrifugal bottom, and factors appearing during the platelet release reaction, were shown to contribute to the SMC growth response. Morphological alterations characteristic of intimal foam cells occurred in SMC grown in VLDL at triglyceride levels in excess of 15 mg per 100 ml. Thus there are distinct parallels between SMC response in this model in vitro and atherogenesis in vivo.
Manipulations of AMP Metabolic Genes Increase Growth Rate and Cold Tolerance in Escherichia coli: Implications for Psychrophilic Evolution
Authors: B. R. Parry, D. H. Shain
Journal: Molecular Biology and Evolution (2011)

Diverse organisms have adapted to thrive at low temperatures (i.e., <20 °C, termed psychrophiles), colonizing the majority of earth's biosphere. In contrast with mesophiles (20-40 °C thermal range), all observed psychrophiles increase intracellular adenosine 5'-triphosphate concentrations as temperatures decline; this phenomenon has been described as an important compensatory mechanism to deal with decreases in thermal energy and molecular motion. We considered purine metabolic pathways in class gammaproteobacteria (n = 115) to investigate metabolic and evolutionary bases of this process. A survey of the KEGG database indicated that psychrophilic purine metabolic pathways tend to be enriched with de novo adenosine 5'-monophosphate (AMP) synthetic enzymes, whereas mesophiles tend to be enriched with AMP degradative enzymes. Function of the observed psychrophilic pathway structure was tested by engineering the mesophilic gammaproteobacterium Escherichia coli to reflect psychrophilic purine metabolism, specifically by expressing adenylosuccinate synthetase (purA) from the psychrophilic gammaproteobacterium, Psychrobacter cryohalolentis, in an AMP nucleosidase (amn)-deficient background. Modified E. coli was capable of growing up to ∼70% faster at low temperatures and became up to ∼10-fold more cold tolerant relative to wild type. These findings highlight potentially important transitional steps in psychrophilic evolution.
Lung bioavailability of generic and innovator salbutamol metered dose inhalers.
Authors: D J Clark, J Gordon-Smith, G McPhate, G Clark, B J Lipworth
Journal: Thorax (1996)

BACKGROUND: The aim of this study was to determine whether significant differences exist in lung bioavailability between generic (Salamol, Salbulin) and innovator (Ventolin) formulations of inhaled salbutamol given by metered dose inhalers. METHODS: Ten healthy volunteers of mean age 20.5 years with a forced expiratory volume in one second (FEV1) of 112.1% predicted were studied in a randomised double blind single dosing crossover study. Salbutamol, 1200 micrograms, was given with mouth rinsing and lung bioavailability was assessed by measuring plasma salbutamol levels and urine excretion of salbutamol. RESULTS: No differences were seen between innovator and generic salbutamol metered dose inhalers in plasma salbutamol levels, urinary salbutamol excretion, or extrapulmonary beta 2 activity. The maximum plasma salbutamol concentration (mean Cmax) and time to maximum concentration (median Tmax) were: Ventolin (2.93 ng/ml, 10 minutes), Salbulin (3.01 ng/ml, 10 minutes), Salamol (3.33 ng/ml, 10 minutes). The geometric mean ratio and 95% confidence interval for Cmax were: Salbulin/Ventolin 1.02 (0.69 to 1.41) and Salamol/Ventolin 1.13 (0.94 to 1.35). CONCLUSIONS: No differences are apparent between the two generic and innovator formulations of salbutamol metered dose inhaler in terms of lung bioavailability.
Immunohistochemical study of adhesion molecules in liver inflammation
Authors: Riccardo Volpes, Joost J. van den Oord, Valeer J. Desmet
Journal: Hepatology (1990)

Using monoclonal antibodies and in situ immunohistochemistry, we studied the distribution of “accessory” adhesion molecules (i.e., intercellular adhesion molecule-1 and leukocyte function–associated antigen-3) in 114 liver biopsy specimens with various inflammatory liver diseases and in 12 control liver biopsy samples without inflammation. The distribution of these adhesion molecules was compared with the presence on inflammatory cells of their natural ligands, lymphocyte function–associated antigen-1 and cluster of differentiation antigen-2, respectively. In normal liver, intercellular adhesion molecule-1 and leukocyte function–associated antigen-3 reacted weakly with sinusoidal lining cells, portal vessel endothelium and scattered mononuclear inflammatory cells, whereas hepatocytes were constantly negative. In contrast, all 114 biopsy samples of acute or chronic liver diseases revealed strong expression of intercellular adhesion molecule-1 and leukocyte function–associated antigen-3 on sinusoidal lining cells and on hepatocytes in areas of inflammation. Hepatocellular membrane positivity resulted in a “honeycomb pattern” of staining, which was panacinar in acute hepatitis and focal in chronic persistent or aggressive hepatitis. In various other chronic liver diseases, a multifocal periportal and intraacinar honeycomb pattern was detected. In all cases, a close topographical correlation was found between hepatocellular expression of intercellular adhesion molecule-1 and leukocyte function–associated antigen-3 on one hand and the presence of inflammatory cells expressing lymphocyte function–associated antigen-1 and cluster of differentiation antigen-2 on the other. These data suggest that in inflammatory liver diseases adhesion between hepatocytes and inflammatory cells is mediated by two different pathways of cellular interaction, involving intercellular adhesion molecule-1/lymphocyte function–associated antigen-1 and leukocyte function–associated antigen-3/cluster of differentiation antigen-2. This may result in increased adherence and may facilitate antigen presentation to and activation of inflammatory cells. In this way, hepatocytes may play an active immunoregulatory role in the recruitment and retention of inflammatory cells during an immune response. (HEPATOLOGY 1990;12:59–65).