tbuckley/cabot-search huggingface dataset:
Suitability of S-phenyl mercapturic acid and trans-trans-muconic acid as biomarkers for exposure to low concentrations of benzene.
Authors: P J Boogaard, N J van Sittert
Journal: Environmental Health Perspectives (1996)

Phenol is not reliable as a biomarker for exposure to benzene at concentrations below 5 ppm (8-hr time-weighted average [TWA]). S-Phenylmercapturic acid (S-PMA) and trans-trans-muconic acid (tt-MA), two minor urinary metabolites of benzene, have been proposed as biomarkers for low-level exposures. The aim of this study was to compare their suitability as biomarkers. S-PMA and tt-MA were determined in 434 urine samples collected from 188 workers in various settings in the petrochemical industry and from 52 control workers with no occupational exposure to benzene. Benzene concentrations in the breathing zone of the potentially exposed workers were assessed by personal air monitoring. Strong correlations were found between S-PMA and tt-MA concentrations in end-of-shift samples and between either of these parameters and airborne benzene concentrations. Exposure to 1 ppm benzene (8-hr TWA) leads to an average concentration in end-of-shift samples of 21 mol S-PMA and 1.5 mmol tt-MA per mol creatinine. Of an inhaled dose of benzene, on average 0.11% (range 0.05-0.26%) was excreted as S-PMA with an apparent elimination half-life of 9.1 (standard error [SE] 0.7) hr and 3.9% (range 1.9-7.3%) as tt-MA with a half-life of 5.0 (SE 0.5) hr. Due to its longer elimination half-life, S-PMA proved a more reliable biomarker than tt-MA for benzene exposures during 12-hr shifts. Specificity of S-PMA, but not tt-MA, was sufficient to discriminate between the 14 moderate smokers and the 38 nonsmokers from the control group. The mean urinary S-PMA was 1.71 (SE 0.27) in smokers and 0.94 (SE 0.15) mol/mol creatinine in nonsmokers (p = 0.013). The mean urinary tt-MA was 0.046 (SE 0.010) in smokers and 0.029 (SE 0.013) mmol/mol creatinine in nonsmokers (p = 0.436). The inferior specificity of tt-MA was due to relatively high background values of up to 0.56 mmol/mol creatinine, which may be found in nonexposed individuals and limits the use of tt-MA to concentrations of benzene over 1 ppm (8-hr TWA). We conclude that S-PMA is superior to tt-MA as a biomarker for low-level benzene exposures because it is more specific, enabling reliable determination of benzene exposures down to 0.3 ppm (8-hr TWA), and because its longer half-life makes it more suited for biological monitoring of operators working in shifts longer than 8 hr.
Studies of "Normality"
Authors: Lila Elveback
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In our paper "Health, Normality, and the Ghost of Gauss" (<i>JAMA</i><b>211</b>:69-75, 1970), we commented that our routine laboratory records contained a larger percentage of hospitalized patients than one would expect from an outpatient clinic. We commented further that we did not know, for any of the seven tests, what that percentage was, or what the effect on the "normal values" as estimated by the Hoffmann method would be. Gambino and McLendon have both commented in letters to the Editor on the importance of eliminating hospitalized patients. Recently we have been able to determine that, of the 3,141 electrophoresis records originally used, 13% were from hospitalized patients. Of the total 3,141 we had found 2.7% and 3.2% of the laboratory protein values misclassified as low and high "Hoffmann false-negative"; for total protein these percentages were 17.8% and 0.8%. In applying the Hoffmann method to the 2,747
GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer
Authors: Christian A. Nebiker, Junyi Han, Serenella Eppenberger-Castori, Giandomenica Iezzi, Christian Hirt, Francesca Amicarella, Eleonora Cremonesi, Xaver Huber, Elisabetta Padovan, Basilio Angrisani, Raoul A. Droeser, Raffaele Rosso, Martin Bolli, Daniel Oertli, Urs von Holzen, Michel Adamina, Manuele G. Muraro, Chantal Mengus, Paul Zajac, Giuseppe Sconocchia, Markus Zuber, Luigi Tornillo, Luigi Terracciano, Giulio C. Spagnoli
Journal: Clinical Cancer Research (2014)

Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization.GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by (3)H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed.GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1β and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance.GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer.
DIAGNOSIS OF LOCALIZED PARASITIC INFECTION BY IMAGING WITH INDIUM-111-LABELED EOSINOPHILS
Authors: J. A. Clanton, V. M. Runge, D. G. Colley, S. J. Anderson, J. S. Cave, C. L. Partain
Journal: Clinical Nuclear Medicine (1983)

Clanton, J. A.; Runge, V. M.; Colley, D. G.; Anderson, S. J.; Cave, J. S.; Partain, C. L. Author Information
Chronic pressure overload is associated with cardiocyte apoptosis, but does not increase vulnerability to β-adrenergic mediated cardiocyte apoptosis
Authors: Y. Shizukuda, E.H. Sonnenblick, D.L. Geenen, A.C. Borczuk, R.N. Kitsis, P.M. Buttrick
Journal: Journal of the American College of Cardiology (1998)
Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication
Authors: Alexandre Florimond, Philippe Chouteau, Patrice Bruscella, Jacques Le Seyec, Emilie Mérour, Nazim Ahnou, Ariane Mallat, Sophie Lotersztajn, Jean-Michel Pawlotsky
Journal: Gut (2014)

<h3>Background</h3> Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. <h3>Objective</h3> To assess whether human HSCs are susceptible to HCV infection. <h3>Design</h3> We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. <h3>Results</h3> In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. <h3>Conclusions</h3> Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
Effect of P-Wave Timing During Supraventricular Tachycardia on the Hemodynamic and Sympathetic Neural Response
Authors: Mohamed H. Hamdan, Jason D. Zagrodzky, Richard L. Page, Stephen L. Wasmund, Clifford J. Sheehan, Mathew M. Adamson, Jose A. Joglar, Michael L. Smith
Journal: Circulation (2001)

Previous studies have shown the importance of the timing of atrial and ventricular systole on the hemodynamic response during supraventricular tachycardia (SVT). However, the reflex changes in autonomic tone during SVT remain poorly understood.Eleven patients with permanent dual-chamber pacemakers were enrolled in the study. Arterial blood pressure (BP), central venous pressure (CVP), and peripheral muscle sympathetic nerve activity (SNA) were recorded during DDD pacing at a rate of 175 bpm (cycle length 343 ms) with an atrioventricular (AV) interval of 30, 200 and 110 ms, simulating tachycardia with near-simultaneous atrial and ventricular systole, short-RP tachycardia (RP<PR), and long-RP tachycardia (RP>PR). Each pacing run was performed for 3 minutes separated by a 5-minute recovery period. All patients demonstrated an abrupt fall in BP, an increase in CVP, and an increase in SNA regardless of the AV interval. The decreases in SBP, DBP, and MAP and the increase in CVP were significantly less during long-RP tachycardia (AV interval 110 ms) than during the other 2 pacing modes (P:<0.05), and the increase in SNA in 7 of the 11 patients was significantly greater during closely coupled atrial and ventricular systole than during long-RP tachycardia (P:<0.05).These data suggest that the superior maintenance of hemodynamic stability during long-RP tachycardia is accompanied by reduced sympathoexcitation, which is primarily mediated by the arterial baroreceptors, with a modest cardiopulmonary vasodepressor effect.
Targeting Cancer Stem Cells and Vasculature by a Novel Anti-Delta-Like 4 Ligand (DLL4) Antibody for Treatment of Triple Negative Breast Cancer.
Authors: W. Yen, M. Fischer, J. Lewicki, A. Gurney, T. Hoey
Journal: Cancer Research (2009)

Abstract Triple negative (ER-, PR- Her2-) breast cancer accounts for 10% of all types of breast cancer and is known to particularly aggressive and refractory to current therapies. Chemotherapeutic agents, such as taxanes, are currently the only treatment option for this type of breast cancer, however, these treatments often result in high rates of local and systemic relapse. It has been suggested that cancer stem cells drive tumor growth and progression and are preferentially resistant to many current therapies. Delta-like 4 ligand (DLL4) is an important component of the Notch signaling pathway which is known to mediate stem cell self-renewal and vascular development. We hypothesized that targeting cancer stem cells and the tumor vasculature by interfering with the DLL4/Notch pathway will improve treatment outcome. We developed anti-DLL4 antibodies that recognize either the human or murine protein and have potent binding and antagonist activities. We have used these antibodies to investigate the role of DLL4 in triple negative breast cancer and to probe the mechanism in tumor and stromal cells in xenograft models derived from primary breast tumors. These studies showed that anti-DLL4 was efficacious as a single agent and in combination with paclitaxel (Taxol) against triple negative breast tumors including a tumor that developed paclitaxel resistance. Gene expression analysis showed that anti-DLL4 affected vascular-related genes in the stroma and Notch target genes in the tumor and stroma. Furthermore, inclusion of anti-DLL4 delayed breast tumor recurrence following termination of paclitaxel treatment. A tumorigenicity study indicated that treatment with anti-DLL4 decreased cancer stem cell frequency as measured by in vivo limiting dilution assay, whereas paclitaxel alone was ineffective. The combination of anti-DLL4 and paclitaxel further decreased cancer stem cell frequency compared to single agents. Our findings provide a rationale for targeting cancer stem cells and tumor vasculature through inhibition of the DLL4/Notch signaling for breast cancer treatment. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5071.
Diffuse Mesothelioma of the Pleura and Asbestos
Authors: P. C. Elmes, W. T. E. McCaughey, O. L. Wade
Journal: BMJ (1965)

Patients with Mesothelioma of the Pleura.-Occupationalhistories were obtained from the patients themselves or, if the patients had died, from friends and neighbours.Including those previously reported, 45 cases of mesothelioma of the pleura had been diagnosed in Belfast by the time this study was completed.Only 42 were included in the analysis because three of the early patients had died more than 15 years previously and no details were available.Control Patients.-Occupationalhistories were obtained from matched controls selected from the records of the department of pathology.If diagnosis of mesothelioma of the pleura in the propositus had been made by biopsy the paired control was selected as that patient of the same sex and within 1 year of age whose name appeared closest to the name of the on 16 July
Respiratory-related Discharge of Genioglossus Muscle Motor Units
Authors: Jooby John, E. Fiona Bailey, Ralph F. Fregosi
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Little is known about the respiratory-related discharge properties of motor units driving any of the eight muscles that control the movement, shape, and stiffness of the mammalian tongue.Objectives: To characterize the respiratory-related discharge of genioglossus motor units as synaptic drive to the hypoglossal motoneuron pool is increased with hypercapnia.Measurements: We recorded airflow, genioglossus muscle EMG activity, and the respiratory-related discharge of 30 genioglossus muscle motor units in spontaneously breathing, urethane-anesthetized rats under control conditions and in hypercapnia (inspired CO2: 3, 6, 9, and 12%, 3–5 min at each level).Main Results: All motor units were active throughout all or most of inspiration. Nine of 30 units showed “preinspiratory” activity (discharge onset within the last 20% of expiration), with continued discharge into inspiration. Six inspiratory units transitioned to a preinspiratory pattern when inspired CO2 exceeded 6%. For the majority of units (23/30), discharge rate increased with hypercapnia, with the maximum increase averaging about 50%. The average variability of interspike intervals within a spike train increased from 33% under baseline conditions to 50% with maximal hypercapnia.Conclusions: (1) The discharge pattern of genioglossus muscle motor units can be altered by hypercapnia; (2) most, but not all, genioglossus motor units receive synaptic input from CO2-sensitive chemoreceptors; (3) individual motor units have a wide range of CO2 sensitivities; and (4) hypercapnia significantly increases the variability of motor unit discharge, which may enhance muscle force output.
Use of the enzyme-linked immunosorbent assay (ELISA) in immunotoxicity testing.
Authors: J G Vos, E I Krajnc, P Beekhof
Journal: Environmental Health Perspectives (1982)

Based on an earlier described macromethod for the routine measurement of IgM and IgG in rat sera, a mechanized micro enzyme-linked immunosorbent assay (ELISA) was developed. The assay was performed in the wells of microtiter plate thus minimizing the quantities of reagents and antisera needed. Data on reproducibility of the assay and calculation of IgM and IgG levels are provided. For the functional assessment of the humoral immunity of the rat, ELISA is a powerful tool. In an earlier report, assays for the titration of thymus-independent IgM antibodies to E. coli LPS and the IgM and IgG response to the thymus-dependent antigen tetanus toxoid were described. More recently it was shown that the antigen ovalbumin elicits a thymus-dependent IgM, IgG and IgE response which could be readily measured with the enzyme immunoassay, as well as a delayed-type hypersensitivity reaction. As the optimum ovalbumin concentration for both types of reactions was the same, it is concluded that the ovalbumin model offers the advantage that both humoral and cellular immunity can be studies simultaneously in the same animal.
ADULT PSYCHIATRIC ILLNESS ASSESSED FOR CHILDHOOD PARENTAL LOSS, AND PSYCHIATRIC ILLNESS IN FAMILY MEMBERS-A STUDY OF 748 PATIENTS AND 250 CONTROLS
Authors: FERRIS N. PITTS, JAY MEYER, MICHAEL BROOKS, GEORGE WINOKUR
Journal: American Journal of Psychiatry (1965)

For various evidences of parental deprivation and family history of psychiatric illness, 748 consecutive psychiatric patients were examined systematically at admission. the sample was characterized and stratified for age, sex, and socioeconomic and marital status; a matched control population was then obtained from consecutive admissions to the general wards of the same hospital. The various psychiatric and control groups were then compared. There were no differences in parental deprivation in childhood but marked differences in the occurrence of psychiatric illness in family members. It is concluded that if environmental factors turn out to outweigh genetic factors in the genesis of psychiatric illnesses, associational environmental, not deprivational ones, are critical.
A CASE OF LYMPHADENOMA WITH CUTANEOUS MANIFESTATIONS.
Authors: J. M. H. MACLEOD
Journal: British Journal of Dermatology (1925)

Journal Article A CASE OF LYMPHADENOMA WITH CUTANEOUS MANIFESTATIONS. Get access J. M. H. MACLEOD, M.D., F. R. C. P. J. M. H. MACLEOD, M.D., F. R. C. P. Physician for Diseases of the Skin, Charing Cross Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 3, 1 March 1925, Pages 119–122, https://doi.org/10.1111/j.1365-2133.1925.tb09935.x Published: 01 March 1925
What Marrow Does to Bone
Authors: Lawrence G. Raisz
Journal: New England Journal of Medicine (1981)

Bone-marrow formation is a remarkable feat. During fetal life, hematopoietic cells leave their soft beds in the liver and spleen and excavate a safer home inside the skeleton. Hence, these cells must have the ability to migrate to the endosteum and subsequently to remove the calcified tissue that fills most of the available space in developing bone. The bone-resorbing cells, which accomplish the latter task, have a different lineage from the osteoblasts', which initially form bone.1 Marrow formation is probably initiated by invasion of vessels that make a path for blood-borne osteolytic cells. The osteolytic cells are derived from monocytic . . .
Canadian women compensated for sterilisation
Authors: O. Dyer
Journal: BMJ (1996)

A Canadian court has awarded a woman $C740 280 (pounds sterling370 140; $555 210) for being sterilised as part of a eugenics programme in the western province of Alberta. The Alberta Eugenics Board was founded in 1928 to apply the Sexual Sterilization Act, by which people classed as “feeble-minded” were forcibly sterilised, often without their knowledge.

Ms Liliana Muir, aged 51, took the provincial government to court …
TROPONIN I IS CHRONICALLY AND PERSISTENTLY ELEVATED IN HOSPITALIZED HEART FAILURE PATIENTS AND IS ASSOCIATED WITH INCREASED MORTALITY OVER FIVE YEARS
Authors: Ravi S. Hira, Maithili Shenoy, Omid Fatemi, Mariana Bolos, Wenyaw Chan, Biykem Bozkurt
Journal: Journal of the American College of Cardiology (2010)
Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.
Authors: T J Raife, D J Lager, K C Madison, W W Piette, E J Howard, M T Sturm, Y Chen, S R Lentz
Journal: Journal of Clinical Investigation (1994)

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.
Cardiovascular Abnormalities Associated with Adult Polycystic Kidney Disease
Authors: CARL V. LEIER
Journal: Annals of Internal Medicine (1984)

In a combined retrospective and prospective study, 11 patients with adult polycystic kidney disease were found to have one or more cardiac or aortic lesions. Seven patients had primary dilatation of the aortic root and annulus with aortic regurgitation. The severity of the aortic regurgitation necessitated aortic valve replacement in 2. Mitral regurgitation was present in 3 patients, of whom 2 had documented redundant mitral leaflets and ruptured chordae tendinae, and the third had mitral valve prolapse. Histologic analysis of available aortic and mitral valve tissue from these acquired lesions showed myxomatous degeneration with loss and disruption of collagen. Four patients had congenital bicuspid aortic valves with aortic regurgitation; 1 of these patients also had mild valvular stenosis, and 1 had coarctation of the aorta.
EARLY DIAGNOSIS OF CARCINOMA OF THE STOMACH BY MEANS OF CHEMIC ANALYSIS OF THE GASTRIC CONTENTS.
Authors: W. C. WEBER
Journal: JAMA (1896)

The question of how to arrive at an early diagnosis of cancer of the stomach is certainly one which has attracted considerable interest in recent years, and hence concentrated efforts in the study of this peculiarly interesting disease. The reason of this becomes apparent in view of the fact that not infrequently cases come under one's observation which present few and indefinite objective symptoms and a vague sense of disturbance in the digestive process as the only subjective symptom of ailments which in their later stages prove unmistakably to be cancerous. To proceed in the ordinary way, to palpate, percuss and gather the history of the case, is insufficient and often ends in negative and disappointing results. Such failures can, to a great extent, be obviated by supplementing the usual method of diagnosis with a process of chemic analysis to which the stomach contents are subjected. The time was, not