tbuckley/cabot-search huggingface dataset:
The origin, kinetics, and characteristics of the kupffer cells in the normal steady state
Authors: RW Crofton, MMC Diesselhoff-Den Dulk, RV Furth
Journal: The Journal of Experimental Medicine (1978)

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.
Staphylococcus aureus Infection of the Nose
Authors: Barry Egener
Journal: JAMA (1986)

<h3>To the Editor.—</h3> I would like to propose an alternative antibiotic therapy for Dr Martin's patient with recurrent<i>Staphylococcus aureus</i>infection of the nose.<sup>1</sup>Your consultant appropriately emphasized the difficulty of eradicating the nasal carrier state. Because of rifampin's unique ability to achieve high concentrations in body secretions, it is very useful for this purpose.<sup>2</sup>However, because many microorganisms can develop one-step resistance through an alteration in the drug target, DNA-dependent RNA polymerase, it is important to combine rifampin with an antistaphylococcal antibiotic. If the patient wears contact lenses, he must be cautioned to remove them during therapy, as similarly high concentrations achieved in lacrimal secretions will permanently stain contact lenses yellow. Finally, if relapse occurs, Dr Martin should consider the possibility that other household members are colonized with the same strain and may be reinfecting the patient. In that case, the risks and benefits of treating the
Reactive Oxygen Species and Diabetic Nephropathy
Authors: Hi Bahl Lee, Hunjoo Ha, George L. King
Journal: Journal of the American Society of Nephrology (2003)

Diabetes is the leading cause of end-stage renal disease worldwide. Intense glycemic and BP control and the use of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers delay but may not prevent or stop the onset and progression of diabetic vascular complications,
Oral Contraceptives, Pregnancy, and Blood Pressure
Authors: Irwin R. Fisch
Journal: JAMA (1972)

Blood pressure was determined for 7,605 women aged 18 to 60. These subjects included 1,941 present users of oral contraceptives, 2,189 never users, and 1,593 past users. Oral contraceptives were associated with a modest yet definite increase in blood pressure, which is related to age and weight but not to drug formulation or dose. This rise was more marked for systolic than diastolic blood pressure. In addition, 953 women in early pregnancy and 247 postpartum subjects had blood pressure readings lower than nonusers. The clinical significance of these findings requires longitudinal study.
Diabetes Mellitus and Macrovascular Complications: An epidemiological perspective
Authors: Richard P Donahue, Trevor J Orchard
Journal: Diabetes Care (1992)

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of β-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
Visualization of the Coronary Sinus in Cineangiocardiography
Authors: FRANK CAMPETI, RAYMOND GRAMIAK, JAMES S. WATSON, GEORGE H. RAMSEY, SYDNEY WEINBERG
Journal: Circulation (1955)

Reflux opacification of the coronary sinus was observed in 25 of 100 cases examined by cineangiocardiography. Of the 25 coronary sinus "positive" cases, 88 per cent were found to have cardiovascular lesions which are regularly associated with severe hypertension of the right heart chambers. The x-ray anatomy of the opacified sinus in different projections, and the movements by which it can be identified on x-ray motion picture films, are described in detail. The meaning of the reflux is discussed in relation to the diagnostic findings.
Regional Flow-Pressure Relationship in Response to Angiotensin in the Intact Dog and Sheep
Authors: N. S. ASSALI, ALLAN WESTERSTEN
Journal: Circulation Research (1961)

The effects of intravenous administration of angiotensin on the arterial pressure and on the renal, carotid, iliac, uterine, and femoral blood flows were investigated in dogs and sheep through the use of implanted electromagnetic flowmeters. The rise in arterial pressure was immediate and, within the range of doses employed, presented little relation ship to the dose. The pressor effect of angiotensin was accompanied by a consistent fall in the renal blood flow and a rise in the femoral, iliac, and uterine flows. Carotid flow was less affected. These studies demonstrate the specificity of flow response to a given change in pressure in the various areas of the body.
PHYSIOTHERAPY IN ORTHOPEDICS
Authors: RICHARD KOVACS
Journal: JAMA (1924)

My object in this paper is to relate in a condensed form the physics and the mode of action of the various physical therapeutic measures as generally used now, and to describe their application in orthopedic conditions in which they are indicated. The unfamiliarity of the average medical practitioner with physical therapeutics is based on the fact that, for the last few decades, no adequate teaching of this important branch of therapy has been given. Eggleston,<sup>1</sup>in 1916, found that, in the model medical curriculum as recommended by the Council on Medical Education, 165 hours were devoted to pharmacology and toxicology, sixteen hours in the third year to nonpharmacal therapeutics, including hydrotherapy, climatology, dietetics, electrotherapeutics, psychotherapy and other physical and physiologic measures, and that fifteen hours in the fourth year to electrodiagnosis and therapeutics. Marvel,<sup>2</sup>in 1912, said: Whence comes most of our knowledge of physical therapeutics? Not
Nevoid Hyperkeratosis of the Nipple and Areola
Authors: Samy Fenniche, Talel Badri
Journal: New England Journal of Medicine (2010)

A 28-year-old woman in her 5th month of pregnancy presented with a 2-month history of asymptomatic, irregular thickening of both nipples and the left areola. On physical examination, both nipples and the left areola were covered with diffuse, hyperpigmented, verrucous plaques with a filiform or papular warty surface (Panel A). Histologic examination revealed orthokeratotic hyperkeratosis, irregular filiform acanthosis, papillomatosis, and keratotic plugging (Panel B, hematoxylin and eosin), all of which are found in nevoid hyperkeratosis of the nipple and areola. The lesions are benign and asymptomatic and thus may not come to medical attention. The cause of nevoid hyperkeratosis of . . .
Methylome-Wide Association Study of Schizophrenia
Authors: Karolina A. Aberg, Joseph L. McClay, Srilaxmi Nerella, Shaunna Clark, Gaurav Kumar, Wenan Chen, Amit N. Khachane, Linying Xie, Alexandra Hudson, Guimin Gao, Aki Harada, Christina M. Hultman, Patrick F. Sullivan, Patrik K. E. Magnusson, Edwin J. C. G. van den Oord
Journal: JAMA Psychiatry (2014)

Epigenetic studies present unique opportunities to advance schizophrenia research because they can potentially account for many of its clinical features and suggest novel strategies to improve disease management.To identify schizophrenia DNA methylation biomarkers in blood.The sample consisted of 759 schizophrenia cases and 738 controls (N = 1497) collected in Sweden. We used methyl-CpG-binding domain protein-enriched genome sequencing of the methylated genomic fraction, followed by next-generation DNA sequencing. We obtained a mean (SD) number of 68 (26.8) million reads per sample. This massive data set was processed using a specifically designed data analysis pipeline. Critical top findings from our methylome-wide association study (MWAS) were replicated in independent case-control participants using targeted pyrosequencing of bisulfite-converted DNA.Status of schizophrenia cases and controls.Our MWAS suggested a considerable number of effects, with 25 sites passing the highly conservative Bonferroni correction and 139 sites significant at a false discovery rate of 0.01. Our top MWAS finding, which was located in FAM63B, replicated with P = 2.3 × 10-10. It was part of the networks regulated by microRNA that can be linked to neuronal differentiation and dopaminergic gene expression. Many other top MWAS results could be linked to hypoxia and, to a lesser extent, infection, suggesting that a record of pathogenic events may be preserved in the methylome. Our findings also implicated a site in RELN, one of the most frequently studied candidates in methylation studies of schizophrenia.To our knowledge, the present study is one of the first MWASs of disease with a large sample size using a technology that provides good coverage of methylation sites across the genome. Our results demonstrated one of the unique features of methylation studies that can capture signatures of environmental insults in peripheral tissues. Our MWAS suggested testable hypotheses about disease mechanisms and yielded biomarkers that can potentially be used to improve disease management.
Non-endoscopic screening biomarkers for Barrett's oesophagus: from microarray analysis to the clinic
Authors: P Lao-Sirieix, A Boussioutas, S R Kadri, M O'Donovan, I Debiram, M Das, L Harihar, R C Fitzgerald
Journal: Gut (2009)

<b>Background:</b> Hyperoxia increases oxidative stress through the generation of reactive oxygen species and may therefore enhance inflammation in the lungs. The aim of this study was to investigate whether short term supplementary oxygen (28%) increases oxidative stress and inflammation in the airways by measuring 8-isoprostane and interleukin 6 (IL-6) concentrations in exhaled breath condensate. <b>Methods:</b> Twenty three healthy subjects (12 men, mean (SD) age 48 (7) years) and 23 patients with chronic obstructive pulmonary disease (COPD; 15 men, mean (SD) age 56 (5) years) were studied. 8-isoprostane and IL-6 concentrations were measured by immunoassay. <b>Results:</b> Increased concentrations of 8-isoprostane and IL-6 were found in all subjects after breathing 28% oxygen for 1 hour. In healthy subjects the concentrations of 8-isoprostane and IL-6 were 10.9 (2.9) pg/ml and 4.9 (0.8) pg/ml, respectively, compared with baseline concentrations of 6.1 (1.3) pg/ml and 2.9 (0.6) pg/ml, and in patients with COPD the concentrations were 27.9 (3.1) pg/ml and 8.3 (1.2) pg/ml), respectively, compared with baseline concentrations of 18.9 (3.6) pg/ml and 6.3 (0.6) pg/ml. By contrast, breathing air through the same face mask for 1 hour had no significant effects on 8-isoprostane or IL-6 concentrations in normal subjects or those with COPD. <b>Conclusions:</b> These findings suggest that short term supplementary oxygen may enhance oxidative stress and inflammation in the airways. Whether this happens with long term oxygen therapy needs to be determined.
Dexamethasone in acute stroke.
Authors: G Mulley, R G Wilcox, J R Mitchell
Journal: BMJ (1978)

Over 13 months 118 patients admitted to hospital with acute stroke were allocated at random to treatment with either dexamethasone or placebo. At one year there was no significant difference in the numbers of survivors or in the quality of life between the two groups. The results suggest that there is no indication for the routine administration of dexamethasone to a heterogeneous group of patients with stroke.
Cyclic Stretch Controls the Expression of CD40 in Endothelial Cells by Changing Their Transforming Growth Factor–β1 Response
Authors: Thomas Korff, Karin Aufgebauer, Markus Hecker
Journal: Circulation (2007)

CD40 is a costimulatory molecule that acts as a central mediator of various immune responses, including those involved in the progression of atherosclerosis. Correspondent to its function, CD40 is present not only on many immune cells, such as antigen-presenting cells and T cells, but also on nonimmune cells, such as endothelial cells.Ex vivo analyses in mice revealed that CD40 is strongly expressed in distinct venous and capillary but not arterial endothelial cell populations. Therefore, we analyzed to what extent determinants of an arterial environment control CD40 expression in these cells. In vitro studies indicated that the presence of smooth muscle cells or exposure to cyclic stretch significantly downregulates CD40 expression in human endothelial cells. Interestingly, endothelial cells cocultured with smooth muscle cells upregulated CD40 expression in response to cyclic stretch through a transforming growth factor-beta1/activin-receptor-like kinase-1 (Alk-1)-dependent mechanism. To corroborate that this mechanism also operates in arteries in vivo, we analyzed the expression of Alk-1 and CD40 at atherosclerosis-prone sites of the mouse aorta that also appear to be exposed to increased stretch. In wild-type mice, both Alk-1 and CD40 revealed a comparably heterogeneous expression pattern along the aortic arch that matched those sites in low-density lipoprotein-receptor-deficient mice where atherosclerotic lesions develop.Cyclic stretch thus increases the abundance of CD40 in endothelial cells through transforming growth factor-beta1/Alk-1 signaling. This mechanism in turn may be responsible for the heterogeneous expression of CD40 at arterial bifurcations or curvatures and would support a site-specific proinflammatory response that is typical for the early phase of atherosclerosis.
Pamela Mary Spencer (nee Bacon)
Authors: C. Spencer, K. Thickett
Journal: BMJ (2011)

Pamela Mary Spencer (nee Bacon) (“Pam”) entered medical school just after the end of the second world war. A place at the Royal Free having been put in doubt at the last minute owing to damage from a V2 rocket, she transferred to University College. She went on to qualify in 1950 and completed junior doctor jobs in surgical specialties in London and Cambridge. Pam gained her FRCS in 1957 and specialised in obstetrics and gynaecology. As senior registrar on the professorial unit in the …
Benzene and Benzin
Authors: Frank McDowell
Journal: JAMA (1963)

To the Editor:  —I am reasonably certain that the title of your recent article,  Exposure and Aplastic Anemia Followed by Leukemia 15 Years Later, (JAMA185:748 [Sept 7] 1963), will cause confusion in the minds of many physicians, nurses, and hospital administrators. Many in these groups confuse benzene (C6H6) with benzine, which is a mixture of a short-chain aliphatic hydrocarbons that is often used in hospitals for removing adhesive tape, and for miscellaneous cleansing jobs.  A few years ago when a similar article did not clearly differentiate between these two different substances, some hospitals erroneously removed benzine from their standard supplies and substituted carbon tetrachloride, which is far more toxic than either benzene or benzine. Perhaps attention should be drawn to this again, to avoid repetition of this common and unfortunate error.  Benzinor, preferably, petroleum benzin is a more acceptable designation than benzine. Benzene
Measuring Patients' Expectations and Requests
Authors: Richard L. Kravitz
Journal: Annals of Internal Medicine (2001)

Patients seeking help for symptoms frequently worry about the underlying causes of their symptoms; have specific expectations for care; and request (or demand) time, information, and services. Understanding patients' concerns, expectations, and requests is important for clinicians, health care policymakers, and researchers. One obstacle to progress in this area has been disagreement over the most appropriate methods for identifying, monitoring, and classifying these phenomena. This article reviews the conceptual relationships linking patients' expectations, requests, and satisfaction with care; surveys contemporary approaches to the measurement of expectations and requests; and highlights recent empirical findings. The literature reviewed supports the conclusion that patients' expectations are wide ranging, can be measured, and have potentially important clinical consequences. For clinicians and policymakers alike, learning to elicit, evaluate, and understand patients' expectations will be a major task for the early part of the new century.
Biology of Mammalian Fertilization and Implantation
Authors: Robert H. Davis
Journal: JAMA (1972)

The editors successfully present the work of distinguished scientists and clinicians who bring together the most recent advances in reproductive biology discussed at a symposium on the physiology and pathology of reproduction, Detroit, 1970. This significant text meets all of the tough, hard-core problems of reproductive biology in a head-on fashion with solid up-to-date evidence, obtained by 21 eminent scholars. They bring to the reader the newest and the most dramatic discoveries in reproductive physiology, implantation, fetal growth and development. They give us the know-how for developing different and better methods of contraception to control the population explosion and environmental pollution, particularly in the newly developed countries where man fights to survive. New possibilities for contraception include inhibiting enzymes involved in sperm capacitation and migration as well as ova penetration, altering ova transport and degeneration, and regulating fertility by immunologic procedures. The implantation-initiating factor obtained from the mouse uterus triggers
Abstract 5489: An amiloride derivative capable of inducing ER stress and cell death in highly invasive breast cancer
Authors: Leonardo J. Leon, William Harley, Kermit Carraway, Fredric Gorin
Journal: Cancer Research (2011)

Abstract Metastasis, which is the spread of tumors from their place of origin to other locations in the body via the lymph or blood, is associated with a significant increase in morbidity and mortality. Studies on amiloride, an FDA-approved diuretic, have shown it to suppress metastatic characteristics such as cell invasion and suppression, and impair their proliferation and viability. Here we show that 38B, a cell-permeant amiloride derivative, is more efficacious at causing cell death of cancer cells than amiloride. We also show that the cell death produced by 38B does not seem to be caused by apoptosis, autophagy, or calcium-dependent necrosis. However, bright field and immunofluorescence microscopy reveal vacuole formation and ER stress in cells, characteristics typically associated with a recently discovered type of cell death known as paraptosis. Since cancer cells have shown to be efficient at evading common forms of cell death such as apoptosis, the discovery of alternative pathways of cell death and a good understanding of the drugs that activate them can be can be key in the improvement of cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5489. doi:10.1158/1538-7445.AM2011-5489
Mitogen- and Stress-Activated Kinase 1–Mediated Histone H3 Phosphorylation Is Crucial for Cell Transformation
Authors: Hong-Gyum Kim, Ki Won Lee, Yong-Yeon Cho, Nam Joo Kang, Sang-Muk Oh, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2008)

Abstract Mitogen- and stress-activated kinase 1 (MSK1) belongs to a family of dual protein kinases that are activated by either extracellular signal-regulated kinase or p38 mitogen-activated protein kinases in response to stress or mitogenic extracellular stimuli. The physiologic role of MSK1 in malignant transformation and cancer development is not well understood. Here, we report that MSK1 is involved in 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced or epidermal growth factor (EGF)–induced neoplastic transformation of JB6 Cl41 cells. H89, a potent inhibitor of MSK1, strongly suppressed TPA-induced or EGF-induced cell transformation. When cells overexpressing wild-type MSK1 were treated with TPA or EGF, colony formation increased substantially compared with untreated cells or cells that did not overexpress MSK1. In contrast, MSK1 COOH terminal or NH2 terminal dead dominant negative mutants dramatically suppressed cell transformation. Introduction of small interfering RNA-MSK1 into JB6 Cl41 cells resulted in suppressed TPA-induced or EGF-induced cell transformation. In addition, cell proliferation was inhibited in MSK1 knockdown cells compared with MSK1 wild-type cells. In wild-type MSK1-overexpressing cells, activator protein (AP-1) activation increased after TPA or EGF stimulation, whereas AP-1 activation decreased in both MSK1 dominant-negative mutants and in MSK1 knockdown cells. Moreover, TPA-induced or EGF-induced phosphorylation of histone H3 at Ser10 was increased in wild-type cells but the induced phosphorylation was abolished in MSK1 dominant-negative mutant or MSK1 knockdown cells. Thus, MSK1 is required for tumor promoter-induced cell transformation through its phosphorylation of histone H3 at Ser10 and AP-1 activation. [Cancer Res 2008;68(7):2538–47]